Bion-M2 PI 1-Pagers

No abstract availabl

Rodent Research Capabilities Update

Space Biology current Rodent Research hardware and capabilities as of October 2017. These include the Life Sciences Glovebox, Rapid Freeze, sample cartridges and simulated carcass freezing, mass measurement device, habitat configuration with enrichment, and the non-Rodent capabilities they feature

Creation and evolution of organocatalytic artificial enzymes

Leven is afhankelijk van chemische reacties die allerlei verschillende functies mogelijk maken, en veel van deze reacties moeten worden versneld omdat ze anders extreem traag zouden zijn. Om dit te bereiken gebruikt de natuur eiwitten (lange ketens van aminozuren die zich vouwen in driedimensionale structuren) genaamd enzymen, die een specifieke organisatie van chemische groepen hebben die het ‘actieve centrum’ of ‘active site’ wordt genoemd. Hier kunnen stoffen binden en door de interacties met het enzym kunnen de reacties met die stoffen worden versneld met een grotere mate van versnelling dan enige mens gemaakte katalysator. De meeste enzymen zijn echter vrij specifiek in welke reacties ze kunnen katalyseren, en zijn simpelweg niet effectief voor veel reacties van maatschappelijk belang. Daarom is er een verlangen om enzymen te creëren die nieuwe soorten reacties kunnen versnellen, en onder deze inspanningen valt het ontwikkelen van zogenaamde 'kunst¬matige enzymen' of ‘artificial enzymes’. In de afgelopen decennia is er een explosieve groei geweest van ontdekte chemische reacties die kunnen worden versneld door kleine organische moleculen, die 'organokatalysatoren' worden genoemd. In dit proefschrift werden onnatuurlijke aminozuren met chemische groepen die in organokatalysatoren voorkomen opgenomen in het 'actieve centrum' van een enzym, door ze in het actieve centrum van een niet-enzymatisch eiwit te installeren om zo kunstmatige enzymen te creëren. Net als natuurlijke enzymen kunnen deze kunstmatige enzymen worden onderworpen aan evolutie om ze efficiëntere katalysatoren te maken

A Glossary of Surrey Words. (A Supplement to No. 12.)

Glosario.-- Surrey. -- Pertenece a la Colección Varia 1800-1950 de The Salamanca Corpus. -- Granville Leveson-Gower, 1838-1895. -- A Glossary of Surrey Words. (A Supplement to No. 12.). -- 1893.[ES]Glosario del dialecto de Surrey. [EN]Surrey dialect glossary

Biocatalytic Friedel-Crafts Reactions

Friedel-Crafts alkylation and acylation reactions are important methodologies in synthetic and industrial chemistry for the construction of aryl-alkyl and aryl-acyl linkages that are ubiquitous in bioactive molecules. Nature also exploits these reactions in many biosynthetic processes. Much work has been done to expand the synthetic application of these enzymes to unnatural substrates through directed evolution. The promise of such biocatalysts is their potential to supersede inefficient and toxic chemical approaches to these reactions, with mild operating conditions - the hallmark of enzymes. Complementary work has created many bio-hybrid Friedel-Crafts catalysts consisting of chemical catalysts anchored into biomolecular scaffolds, which display many of the same desirable characteristics. In this Review, we summarise these efforts, focussing on both mechanistic aspects and synthetic considerations, concluding with an overview of the frontiers of this field and routes towards more efficient and benign Friedel-Crafts reactions for the future of humankind

Rodent Research on ISS NASA Update: Joint Working Group

No abstract availabl

Rodent Research: Implementation of an Immunology Experiment on the ISS

No abstract availabl

Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel-Crafts Alkylase

[Image: see text] The construction and engineering of artificial enzymes consisting of abiological catalytic moieties incorporated into protein scaffolds is a promising strategy to realize non-natural mechanisms in biocatalysis. Here, we show that incorporation of the noncanonical amino acid para-aminophenylalanine (pAF) into the nonenzymatic protein scaffold LmrR creates a proficient and stereoselective artificial enzyme (LmrR_pAF) for the vinylogous Friedel–Crafts alkylation between α,β-unsaturated aldehydes and indoles. pAF acts as a catalytic residue, activating enal substrates toward conjugate addition via the formation of intermediate iminium ion species, while the protein scaffold provides rate acceleration and stereoinduction. Improved LmrR_pAF variants were identified by low-throughput directed evolution advised by alanine-scanning to obtain a triple mutant that provided higher yields and enantioselectivities for a range of aliphatic enals and substituted indoles. Analysis of Michaelis–Menten kinetics of LmrR_pAF and evolved mutants reveals that different activities emerge via evolutionary pathways that diverge from one another and specialize catalytic reactivity. Translating this iminium-based catalytic mechanism into an enzymatic context will enable many more biocatalytic transformations inspired by organocatalysis

Rodent Habitat on ISS: Advances in Capability for Determining Spaceflight Effects on Mammalian Physiology

Rodent research is a valuable essential tool for advancing biomedical discoveries in life sciences on Earth and in space. The National Research Counsel's Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, new flight hardware, operations, and science capabilities were developed at NASA ARC to support commercial and government-sponsored research. The flight phases of two separate spaceflight missions (Rodent Research-1 and Rodent Research-2) have been completed and new capabilities are in development. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 was dedicated to achieving both NASA validation and CASIS science objectives, while Rodent Reesearch-2 extended the period on orbit to 60 days. Groundbased control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis, and post-flight quantitative analyses of behavior were performed. The 10 mice from RR-1 Validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully, and high quality RNA (RIN values>9) and liver enzyme activities were obtained, validating the quality of sample recovery. Post-flight sample analysis revealed that body weights of FLT animals did not differ from ground controls (GC) housed in the same hardware, or vivarium controls (VIV) housed in standard cages. Organ weights analyzed post-flight showed that there were no differences between FLT and GC groups in adrenal gland and spleen weights, whereas FLT thymus and liver weights exceeded those of GC. Minimal differences between the control groups (GC and VIV) were observed. In addition, Over 3,000 aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for the Biospecimen Sharing Program and Genelab project. New capabilities recently developed include DEXA scanning, grip strength tests and male mice. In conclusion, new capability for long duration rodent habitation of group-housed rodents was developed and includes in-flight sample collection, thus avoiding the complication of reentry. Results obtained to date reveal the possibility of striking differences between the effects of short duration vs. long duration spaceflight. This Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASAs Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASAs GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLabs open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the programs capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISSs capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Councils Decadal Survey released in 2011 and to maximize science return from each mission