Mouse Behavior on ISS: The Emergence of a Distinctive, Organized Group Circling Behavior Unique to Spaceflight

As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. Only a handful of papers have previously reported behavior of mice and rats in the weightless environment of space (Andreev-Andrievskiy, et al., 2013; Cancedda et al., 2012; Ronca et al., 2008). The Rodent Research Hardware and Operations Validation Mission (Rodent Research-1; RR1) utilized the Rodent Habitat (RH) developed at NASA Ames Research Center to fly mice on the ISS. Ten adult (16-week-old) female C57BL6J mice were launched on September 21st, 2014 in an unmanned Dragon Capsule, and spent 37 days in flight. Here we report group behavioral phenotypes of the RR1 Flight (FLT) and environment-matched Ground Control (GC) mice in the RH during this long duration flight. Video was recorded for 34 days on the ISS, permitting daily assessments of overall health and well being of the mice, and providing a valuable repository for detailed behavioral analysis. As compared to GC mice, RR1 FLT mice exhibited the same range of behaviors, including eating, drinking, exploration, self- and allogrooming, and social interactions at similar or greater levels of occurrence. Overall activity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized circling or race-tracking behavior that emerged within the first few days of flight following a common developmental sequence, comprising the primary dark cycle activity of FLT mice. Circling participation by individual mice persisted throughout the mission. Analysis of group behavior over mission days revealed recruitment of mice into the group phenotype, coupled with decreasing numbers of collisions between circling mice. This analysis provides insights into the behavior of mice in microgravity, and clear evidence for the emergence of a distinctive, organized group behavior unique to the weightless space environment. Supported by the NASA Rodent Research Project, Space Biology Program, and Space Life Sciences Training Program

Rodent Habitat On ISS: Spaceflight Effects On Mouse Behavior

The NASA Decadal Survey (2011), Recapturing a Future for Space Exploration: Life and Physical Sciences Research for a New Era, emphasized the importance of expanding NASA life sciences research to long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities supporting mouse studies in space were developed at NASA Ames Research Center. The first flight experiment carrying mice, Rodent Research Hardware and Operations Validation (Rodent Research-1), was launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4, exposing the mice to a total of 37 days in space. Ground control groups were maintained in environmental chambers at Kennedy Space Center. Mouse health and behavior were monitored for the duration of the experiment via video streaming. Here we present behavioral analysis of two groups of five C57BL/6 female adult mice viewed via fixed camera views compared with identically housed Ground Controls. Flight (Flt) and Ground Control (GC) mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions at similar or greater levels of occurrence. Mice propelled themselves freely and actively throughout the Habitat using their forelimbs to push off or by floating from one cage area to another, and they quickly learned to anchor themselves using tails and/or paws. Overall activity was greater in Flt as compared to GC mice, with spontaneous ambulatory behavior including the development of organized circling or race-tracking behavior that emerged within the first few days of flight and encompassed the primary dark cycle activity for the remainder of the experiment. We quantified the bout frequency, duration and rate of circling with respect to characteristic behaviors observed in the varying stages of the progressive development of circling: flipping utilizing two sides of the habitat, circling, multi-lap circling and group-circling. Once begun, mice did not regress to flipping behavior or other previous behavioral milestones for the remainder of flight. An overall upward trend in circling frequency, rate, duration, participation, and organization was observed over the course of the 37-day spaceflight experiment. In this presentation, we will summarize qualitative observations and quantitative comparisons of mice in microgravity and 1g conditions. Behavioral analyses provide important insights into the overall health and adaptation of mice to the space environment, and identify unique behaviors and social interactions to guide future habitat development and research on rodents in space

Estrous Cyclicity in Mice During Simulated Weightlessness

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n=22), normally loaded HU Cage Pair-Fed controls (CPF; n=22), and Vivarium controls fed ad libitum (VIV; n=10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8+/- 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, and/or due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5% vs 3.0%, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system. Research supported by NNX15AB48G to JST

Analysis of High-order Social Interaction of Female Mice on the International Space Station

Social interactions are adaptive responses to environmental pressures that have evolved to facilitate the success of individual animals and their progeny. Quantifying social behavior in social animals is therefore one method of evaluating an animal's health, wellbeing and their adjustment to changes in their environment. The interaction between environment and animal can influence numerous other physiological and psychological responses that may enhance, deter or shift an animals social paradigm. For this study, we utilized flight video from the Rodent Research Hardware and Operations Validation mission (Rodent Research-1; RR1) on the International Space Station (ISS). Female mice spent 37 days in microgravity on the ISS and video was captured during the final 33 days. In a previous analysis of individual behavior, we also reported an observed spontaneous ambulatory behavior which we termed circling or 'race tracking,' and we anecdotally observed an increase in group organization around this behavior. In this analysis we further examined this behavior, and other social interactions, to determine if (1) animals joining in on this behavior were induced by other cohort members already participating in this circling behavior, (2) rates of joining varied by number already participating

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Unusual electric field effects in Nd<SUB>0.7</SUB>Sr<SUB>0.3</SUB>MnO<SUB>3</SUB>

Enhanced electric field (E) induced modulation of the resistance of epitaxial thin films of Nd0.7Sr0.3MnO3 has been observed. The results show several remarkable features: first, field-direction-independent decrease of the resistance above the temperature at which the peak in resistivity occurs (Tp); second, proportionality of the modulation to E2; third, a reduction in the magnitude and field-direction-independent reversal of the sign of &#916;R/R just below Tp; and fourth, a prompt time response at high temperatures and a slower response near Tp. These results are consistent with a model of a polarization-induced lattice distortion coupling with both spin and charge transport

Jockey riding racehorse Deputy Ruler onto the racecourse, New South Wales, 1933 [picture].

Title devised from accompanying information where available.; Part of the: Fairfax archive of glass plate negatives.; Fairfax number: .; Also available online at: http://nla.gov.au/nla.pic-vn6265372; Acquired from Fairfax Media, 2012