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Obesity is rapidly increasing within the global population and is one of the leading causes of chronic diseases, including type 2 diabetes (T2D), non-alcoholic fatty liver disease, and cardiovascular diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as promising therapeutic agents for treating T2D and obesity. However, the route of administration of the GLP-1R agonists is currently by injection or high oral dosages of the therapeutic combined with absorption enhancers. Oral delivery of GLP-1R agonists remains the preferred administration route due to convenience and high patient compliance. Thus, strategies to improve the oral delivery of this therapeutic are needed. In this study, we engineered the probiotic yeastSaccharomyces boulardiistrain to produce Exendin-4, a GLP-1R agonist, in the gastrointestinal tract to reduce the adverse effects of diet-induced obesity in male C57BL/6 mice. The biological efficiency of the secreted Exendin-4 fromS. boulardiiwas characterisedex vivoon isolated pancreatic islets, demonstrating induced insulin secretion. Furthermore,in vivocharacterisation of the engineered strain identified a synergistic effect of cold exposure and Sb-Exe4 by successfully inhibiting appetite and promoting body weight loss under cold exposure (8°C). In addition, the combination of cold and Sb-Exe4 improved the glucose and lipid homeostasis in the mice by increasing the circulating glucagon level and reducing the inflammatory marker TNF-α. Our results demonstrate thatS. boulardiican be genetically modified to secrete and deliver active therapeutic GLP-1R agonists in the gastrointestinal tract improving the metabolism of the host.

Mouse models are commonly used to study the colonisation profiles of microorganisms introduced to the gastrointestinal tract. Three commonly used mouse models include conventional, germ-free, and antibiotic-treated mice. However, colonisation resistance in conventional mice and specialised equipment for germ-free mice are usually limiting factors in their applications. In this study, we sought to establish a robust colonisation model for Saccharomyces boulardii, a probiotic yeast that has caught attention in the field of probiotics and advanced microbiome therapeutics. We characterised the colonisation of S. boulardii in conventional mice and mice treated with a cocktail of broad-spectrum antibiotics, including ampicillin, kanamycin, metronidazole and vancomycin. We found colonisation levels increased up to 10,000-fold in the antibiotic-treated mice compared to nonantibiotic-treated mice. Furthermore, S. boulardii was detected continuously in more than 75% of mice for 10 days after the last administration in antibiotic-treated mice, in contrast to in nonantibiotic-treated mice where S. boulardii was undetectable in less than 2 days. Finally, we demonstrated that this antibiotic cocktail can be used in two commonly used mouse strains, C57BL/6 and ob/ob mice, both achieving ~ 108 CFU/g of S. boulardii in faeces. These findings highlight that the antibiotic cocktail used in this study is an advantageous tool to study S. boulardii based probiotic and advanced microbiome therapeutics.

At 01:57:20 UTC on October 3rd, 2018, after 3½ years of cruise aboard the JAXA spacecraft HAYABUSA2 and about 3 months in the vicinity of its target, the MASCOT lander was separated successfully by from an altitude of 41 m. After a free-fall of only ~5m51s MASCOT made first contact with C-type near-Earth and potentially hazardous asteroid (162173) Ryugu, by hitting a big boulder. MASCOT then bounced for ~11m3s, in the process already gathering valuable information on mechanical properties of the surface before it came to rest. It was able to perform science measurements at 3 different locations on the surface of Ryugu and took many images of its spectacular pitch-black landscape. MASCOT’s payload suite was designed to investigate the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties of the surface. Somewhat unexpectedly, MASCOT encountered very rugged terrain littered with large surface boulders. Observing in-situ, it confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the HAYABUSA2 spacecraft. After some 17h of operations, MASCOT‘s mission ended with the last communication contact as it followed Ryugu’s rotation beyond the horizon as seen from HAYABUSA2. Soon after, its primary battery was depleted. We present a broad overview of the recent scientific results of the MASCOT mission from separation through descent, landing and in-situ investigations on Ryugu until the end of its operation and relate them to the needs of planetary defense interactions with asteroids. We also recall the agile, responsive and sometimes serendipitous creation of MASCOT, the two-year rush of building and delivering it to JAXA’s HAYABUSA2 spacecraft in time for launch, and the four years of in-flight operations and on-ground testing to make the most of the brief on-surface mission.

For the Planetary Defense Conference Exercise 2019, we set out to find ways to obtain the earliest possible characterization of the incoming (fictitious!) asteroid, 2019 PDC. After a partially successful deflection, a 'small' fragment was still bound for impact. The location was only known two weeks before impact - the time left for the evacuation of the larger New York City metropolitan region. With experience in Near-Earth Object (NEO) exploration mission design, solar sail and solar-electric propulsion (SEP) technology for small spacecraft, agile responsive design and integration, and from previous PDC Exercises, the importance of earliest possible information on impact location and energy was obvious. NEO in-situ exploration can provide invaluable information not just for deflection actions but also for planetary science and resource utilization. This is only possible with space missions closely approaching the asteroid. Expecting a solar sail mission flying in the 2020s could be re-directed, a unique feature of solar sailing, we searched for multiple rendezvous missions at initial sail technology characteristic accelerations of =2 years, within

For now, the Planetary Defense Conference Exercise 2021's incoming fictitious(!) asteroid, 2021 PDC, seems headed for impact on October 20th, 2021, exactly 6 months after its discovery. Today (Monday, April 26th, 2021), the impact probability is 5%, in a steep rise from 1 in 2500 upon discovery six days ago. We all know how these things end. Or do we? Unless somebody wants to keep civil defense very busy very soon, the chance is 95% that it will not hit; instead fly by closely to Earth, swing by to a new orbit that takes it away essentially forever or back again sooner or later through a keyhole, for a re-play at different odds. This is where our story starts and the story sounds familiar: season's greetings from 2004 MN4, now better known as (99942) Apophis. One more thing is similar: the close fly-by is an easy launch opportunity to 'jump aboard' that potentially hazardous asteroid for planetary science and tracking of longterm Yarkovsky-shifted keyhole resonant return risks. Indeed, missions are currently being discussed to launch during the 2029 fly-by of Apophis to rendezvous and investigate it closely right after. Others strive for an earlier launch to rendezvous well before, to observe all of the close fly-by at Earth and what it might do to a likely delicate rubble pile asteroid. Presently, this is an unlikely if not impossible option for sudden encounters like 2021 PDC with a lead time of months. But when asteroid mining (...possibly the other ...-not-if of asteroids?) takes off in the same manner as low Earth orbit communications satellites, this option may become a reality. But for now, even if a suitable planetary mission were serendipitously ready atop a suitable launch vehicle, could you get it an asteroid lander within 6 months? Surprisingly, this option existed between late 2014 and late 2018 when the MASCOT Qualification Model turned Flight Spare was kept fully integrated and flight ready for on-ground testing to prepare for the Flight Model's brief but complete mission on Ryugu with JAXA's highly successful HAYABUSA2 probe. At the same time, the MASCOT2 detailed design study for ESA's former AIM mission within the common NASA-ESA AIDA mission to (65803) Didymos and its moonlet, Dimorphos (then affectionately known as 'Didymoon'), paved the way for long-life MASCOTs, many of which have been discussed and studied since. The thoughtful design of MASCOT’s hardware and software allowed for a very high degree of re-use and flexibility regarding scientific payloads. MASCOT2 was to investigate the interior of Didymoon by Low-Frequency Radar. Close encounters like Apophis' offer unique opportunities for Earth-based planetary radar assets to work with spacecraft near and landers on the passing asteroid. We present a range of options for radar- and composition-oriented long-life MASCOT variants - to be delivered to the surfaces of the respective asteroid bodies - for the presently most likely near miss of 2021 PDC and the most certain close fly-by of (99942) Apophis on Friday, April 13th, 2029.