Vomocytosis: Too Much Booze, Base, or Calcium?

Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and typically break down internalized cargo into small macromolecules. However, some pathogenic agents have the ability to evade this endosomal degradation through a nonlytic exocytosis process termed vomocytosis. This phenomenon has been most often studied for Cryptococcus neoformans, a yeast that causes roughly 180,000 deaths per year, primarily in immunocompromised (e.g., human immunodeficiency virus [HIV]) patients. Existing dogma purports that vomocytosis involves distinctive cellular pathways and intracellular physicochemical cues in the host cell during phagosomal maturation. Moreover, it has been observed that the immunological state of the individual and macrophage phenotype affect vomocytosis outcomes. Here we compile the current knowledge on the factors (with respect to the phagocytic cell) that promote vomocytosis of C. neoformans from macrophages

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Advancing the understanding and measurement of phagocyte vomocytosis of Cryptococcus neoformans

Following digestion by phagocytes, the fungal pathogen Cryptococcus neoformans (CN) has been observed to survive within the normally fatal phagosome and trigger nonlytic expulsion through a process called “vomocytosis”. This phenomenon is believed to play a key role in dissemination of the fungal pathogen, allowing CN to use immune cells as shuttles to travel throughout the body and to even cross the blood brain barrier through a “Trojan Horse” method. Very little is known about the underlying mechanisms of vomocytosis; however, prior studies have correlated its rate of occurrence with a limited number of physicochemical, protein, and immunological cues. Understanding vomocytosis could open the doors for the discovery of new therapies against Cryptococcal infection, as well as the development of novel drug delivery biomaterial vehicles with the ability to escape phagosome-mediated degradation. The primary goal of this thesis is to uncover further understanding of vomocytosis. This work contains (i) the discovery and characterization of this phenomenon’s occurrence in dendritic cells, a key player in bridging the innate and adaptive immune system, (ii) the development of a new fluorescent tool to measure vomocytosis rates in an objective, high throughput manner, and (iii) transcriptomic analysis of CN-infected phagocytes for identification of potential pathways and genes that regulate this process

Stimuli-Responsive Biomaterials for Vaccines and Immunotherapeutic Applications.

The immune system is the key target for vaccines and immunotherapeutic approaches aimed at blunting infectious diseases, cancer, autoimmunity, and implant rejection. However, systemwide immunomodulation is undesirable due to the severe side effects that typically accompany such strategies. In order to circumvent these undesired, harmful effects, scientists have turned to tailorable biomaterials that can achieve localized, potent release of immune-modulating agents. Specifically, "stimuli-responsive" biomaterials hold a strong promise for delivery of immunotherapeutic agents to the disease site or disease-relevant tissues with high spatial and temporal accuracy. This review provides an overview of stimuli-responsive biomaterials used for targeted immunomodulation. Stimuli-responsive or "environmentally responsive" materials are customized to specifically react to changes in pH, temperature, enzymes, redox environment, photo-stimulation, molecule-binding, magnetic fields, ultrasound-stimulation, and electric fields. Moreover, the latest generation of this class of materials incorporates elements that allow for response to multiple stimuli. These developments, and other stimuli-responsive materials that are on the horizon, are discussed in the context of controlling immune responses

Stimuli-Responsive Biomaterials for Vaccines and Immunotherapeutic Applications.

The immune system is the key target for vaccines and immunotherapeutic approaches aimed at blunting infectious diseases, cancer, autoimmunity, and implant rejection. However, systemwide immunomodulation is undesirable due to the severe side effects that typically accompany such strategies. In order to circumvent these undesired, harmful effects, scientists have turned to tailorable biomaterials that can achieve localized, potent release of immune-modulating agents. Specifically, "stimuli-responsive" biomaterials hold a strong promise for delivery of immunotherapeutic agents to the disease site or disease-relevant tissues with high spatial and temporal accuracy. This review provides an overview of stimuli-responsive biomaterials used for targeted immunomodulation. Stimuli-responsive or "environmentally responsive" materials are customized to specifically react to changes in pH, temperature, enzymes, redox environment, photo-stimulation, molecule-binding, magnetic fields, ultrasound-stimulation, and electric fields. Moreover, the latest generation of this class of materials incorporates elements that allow for response to multiple stimuli. These developments, and other stimuli-responsive materials that are on the horizon, are discussed in the context of controlling immune responses