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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
NASA NTRS1993

Improved inhalation technology for setting safe exposure levels for workplace chemicals

Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

Stuart, Bruce O.↗
NASA NTRS2002

Space flight and oxidative stress

Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

long duration↗
NASA NTRS1988

The effects of feedback lighting on the circadian drinking rhythm in the diurnal new world primate Saimiri sciureus

Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior. This technique has previously been used to test the nonparametric model of entrainment in nocturnal rodents. In three species (Rattus norvegicus, Mesocricetus auratus, and Mus musculus), the free-running period of the locomotor activity rhythm was similar whether the animals were exposed to continuous light or discrete light pulses occurring essentially only during the subjective night (i.e., feedback lighting). In the current experiments, feedback lighting was presented to squirrel monkeys so that light fell predominantly during the subjective night. Feedback lighting was linked to the drinking behavior in this diurnal primate so that when the animal drank, the lights went out. Despite the seemingly adverse predicament, the monkeys maintained regular circadian drinking rhythms. Furthermore, just as the period of the free-running activity rhythms of nocturnal rodents exposed to continuous light or feedback lighting were similar, the period of the drinking rhythms of the squirrel monkeys in continuous light and feedback lighting were comparable (25.6 +/- 0.1 and 25.9 +/- 0.1 hours, respectively), despite a substantial decrease in the total amount of light exposure associated with feedback lighting. The free-running period of monkeys exposed to continuous dark (24.5 +/- 0.1 hours) was significantly shorter than either of the two lighting conditions (P < 0.001). The results presented for the drinking rhythm were confirmed by examination of the temperature and activity rhythms. Therefore, discrete light pulses given predominately during the subjective night are capable of simulating the effects of continuous light on the free-running period of the circadian rhythms of a diurnal primate. The response of squirrel monkeys to feedback lighting thus lends further support for the model and suggests that the major entrainment mechanisms are similar in nocturnal rodents and diurnal primates.

NASA Discipline Number 40-30↗
NASA NTRS2000

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS1996

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

NASA Discipline Musculoskeletal↗
NASA NTRS2004

The Hindlimb Unloading Rat Model: Literature Overview, Comparison with Spaceflight Data, and Technique Update

The hindlimb unloading (HU) rodent model is used extensively to study the response of many physiological systems to certain aspects of spaceflight, as well as to disuse and recovery from disuse for Earth benefits. This chapter describes the evolution of HU, and is divided into three sections. The first section examines the characteristics of 1063 articles using or reviewing the HU model, published between 1976 and April 1, 2004. The characteristics include number of publications, journals, countries, major physiological systems, method modifications, species, gender, genetic strains and ages of rodents, experiment duration, and countermeasures. The second section provides a comparison of results between space flown and Hu animals from the 14-day Cosmos 2044 mission. The final section describes modifications to HU required by different experimental paradigms and a method to protect the tail harness for long duration studies. HU in rodents has enabled improved understanding of the responses of the musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and reproductive systems to unloading and/or to reloading on Earth with implications for both long-duration human spaceflight and disuse on Earth.

Morey-Holton, Emily↗
NASA NTRS2005

The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data

The hindlimb unloading rodent model is used extensively to study the response of many physiological systems to certain aspects of space flight, as well as to disuse and recovery from disuse for Earth benefits. This chapter describes the evolution of hindlimb unloading, and is divided into three sections. The first section examines the characteristics of 1064 articles using or reviewing the hindlimb unloading model, published between 1976 and April 1, 2004. The characteristics include number of publications, journals, countries, major physiological systems, method modifications, species, gender, genetic strains and ages of rodents, experiment duration, and countermeasures. The second section provides a comparison of results between space flown and hindlimb unloading animals from the 14-day Cosmos 2044 mission. The final section describes modifications to hindlimb unloading required by different experimental paradigms and a method to protect the tail harness for long duration studies. Hindlimb unloading in rodents has enabled improved understanding of the responses of the musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and reproductive systems to unloading and/or to reloading on Earth with implications for both long-duration human space flight and disuse on Earth.

Flight Experiment↗
NASA NTRS2016

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

skeleton↗
NASA NTRS2017

Mouse Behavior on ISS: The Emergence of 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. Overallactivity was greater in FLT as compared to GC mice, with spontaneous ambulatory behavior, including organized circling or race-tracking behavior that emerged within thefirst few days of flight following a common developmental sequence, comprising theprimary dark cycle activity of FLT mice. Circling participation by individual micepersisted 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.

mice↗
NASA NTRS2017

NASA Ames Institutional Scientific Collection (ISC)

NASA's current human space flight research is directed towards enabling human space exploration beyond Low Earth Orbit (LEO). The Space Flight Payload Projects; Rodent Research, Cell Science, and Microbial Labs, flown on the International Space Station (ISS), benefit both the global life sciences and commercial space communities. Verified data sets, science results, peer-reviewed publications, and returned biospecimens, collected and analyzed for flight and ground investigations, are all part of the knowledge base within NASA’s Human Exploration and Operations Mission Directorate’s Space Life and Physical Sciences Research and Applications (SLPSRA) Division, specifically the Human Research and Space Biology Programs. These data and biospecimens are made available through the public LSDA website. The Ames Institutional Scientific Collection (ISC), or ARC Biobank, stores flight and ground biospecimens from Space Shuttle and ISS programs. These specimens are curated and managed by the Ames Life Sciences Data Archive (ALSDA), an internal node of NASA's Life Sciences Data Archive (LSDA). The ARC Biolbank stores over 15,000 specimens from experiments dating from 1984 to present. Currently available specimens include tissues from the circulatory, digestive, endocrine, excretory, integumentary, muscular, neurosensory, reproductive, respiratory and skeletal systems. The most recent contributions include RNA, DNA and protein extracts from Rodent Research 1 and tissues from Rodent Research 4. NASA's biospecimen collection represents a unique and limited resource. The use of these biospecimens maximizes utilization and scientific return from these unique spaceflight payload and ground control research subjects. These biospecimens are harvested following complex, costly NASA research activities to meet primary scientific objectives. Once the primary scientific objectives have been met, the remaining specimens are made available to provide secondary opportunities for complementary studies or new investigations to broaden research without large expenditures of time or resources. Innovative ways of sharing this information ultimately advances the frontiers of human space exploration as well as scientific understanding of the effects of gravity on life on earth.

French, Alison J.↗
NASA NTRSDate not supplied

Circulating miRNA Signature Predicts and Rescues Spaceflight Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated and real spaceflight and regulates vascular damage by simulated deep space radiation. In previous studies, we identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have validated the expression of key spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twin Study. We demonstrate that this circulating miRNA siganture is conserved between these different species and will serve as an ideal biomarker to monitor increase health risk due to exposure to the space environment. Lastly, to demonstrate their physiological relevance, we have utilized antagomirs to target a subset of miRNAs from the spaceflight associated signature to successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs. These results provide strong evidence to further develop a miRNA based countermeasure in astronauts.

Afshin Beheshti↗
NASA NTRS2020

Circulating Mirna Spaceflight Signature Reveals Targets to Mitigate Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration, and long-duration spaceflight and regulates vascular damage caused by simulated deep space radiation. In previous studies, we had identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have confirmed the expression of these proposed spaceflight associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twins Study via direct quantification of miRNAs, miRNA sequencing, and inferring miRNA target levels based on single-cell RNA (scRNA-seq) and single-cell chromatin (scATAC-seq) sequencing data. To demonstrate the physiological relevance of key spaceflight associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs.

Sherina Malkani↗
NASA NTRS2021

Quirky Circling Behavior in Mice Informs Research on Humans in Space

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. We previously conducted a detailed phenotypic analysis of mouse behavior during long duration (33-day) spaceflight in the NASA Rodent Habitat (Rodent Research-1; RR1 mission). Notably, we documented the emergence within the 8-10 days of launch of spontaneous ambulatory behavior in the form of circling or ‘race-tracking’ behavior in spaceflight but not in an identical ground control condition. Circling is unique to the NASA RH not having been reported to occur in other mouse habitats that provide limited opportunity for grasping, and/or are characterized by smaller habitable volumes viz., Italian Mice Drawer System (MDS) flown on ISS; Russian Block Obespecheniya Soderzhaniya (BOS) flown on Bion M-1, or JAXA Habitat Cage Unit (HCU) flown in the ISS Kibo module. Over time, circling became the primary dark cycle activity of FLT mice, occurring in individuals then as a coordinated group activity. Here we discuss possible interpretations of circling behavior including: (1) Stereotypic or abnormal repetitive behaviors (ARBs) that are unvarying, and apparently functionless behavior patterns documented numerous species in laboratory and zoo settings, possibility related to insufficient environmental enrichment and stress, (2) Rewarding effects of physical activity that are well-documented in terrestrial studies of rodents given the opportunity to run in wheels, and (3) Vestibular self-stimulation, i.e., the generation biologically-relevant amounts of vestibular sensory input to reduce the effects of microgravity. Affording mice the opportunity to grab and run in the RH resembles physical activities that the crew participate in routinely. Our approach is yielding an interesting analogue for better understanding human responses to spaceflight, and providing the opportunity to begin to address how physical movement influences responses to microgravity.

spaceflight↗
NASA NTRSDate not supplied

Inception of a Spaceflight-specific Mouse to Human Expression Profiling Translation Model

Rodents are foundational model organisms often utilized due to their seemingly analogous morphologies and biological responses to humans. However, recent studies have demonstrated that murine model data are limited in their applicability, particularly in inflammatory disease. In space studies, accurately predicting human response from mouse data is critical due to extreme limiting factors in both rodent and human spaceflight research. With successful prediction, spaceflight ailments can be predicted and prevented while respecting the constraints of the spaceflight industry and minimizing danger to humans. To do so, novel methodologies must be developed that predict human response from murine data after considering biological differences between rodents and humans in spaceflight. After considering terrestrial models, we determined that a spaceflight-based expression profiting translation tool should be created to accurately capture predictions of human gene expression in spaceflight from mouse data. To prepare to build this model, we organized known human spaceflight risks, chose analog human diseases as training data categories, then identified existing RNASeq disease datasets from GEO as potential training data. In addition, we classified existing Genelab mouse differential gene expression datasets for use as experimental data.

Translation↗
DOE OSTI2017

The changes in glucose metabolism and cell proliferation in the kidneys of polycystic kidney disease mini-pig models

The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The activities of mitochondrial respiration chain Complexes I and IV significantly decreased; the phosphorylation level of key metabolism-modulating molecule AMP-activated protein kinase (AMPK) significantly decreased; and the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling pathway are activated obviously. This study showed that in the kidneys of PKD mini-pigs, the level of glycolysis significantly increased, oxidative phosphorylation significantly decreased, and cell proliferation signaling pathways significantly activated, suggesting that metabolic changes in PKD may result in the occurrence and development of PKD through the activation of proliferation signaling pathways. - Highlights: • Mini-pigs are more similar to humans than rodents and are an ideal animal model. • The study was first performed in chronic model created by knock-outing PKD1gene. • We investigated the changes in glucose metabolism and cell proliferation. • The glycolysis was significantly increased in the kidneys of PKD mini-pigs. • The mTOR and ERK signaling pathway are activated obviously in PKD mini-pigs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Nerve agent intoxication: Recent neuropathophysiological findings and subsequent impact on medical management prospects

This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3 months after soman poisoning. Indeed, an increased proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents. - Highlights: > This review focuses on neuropathophysiology following nerve agent poisoning in mice. > Extensive data on long-term neuropathology and related inflammation are provided here. > Delayed self-repair attempts encountered in lesioned rodent brains are also described. > Cell therapy is considered as a valuable treatment against nerve agent intoxication.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Subunit Stabilization and Polyethylene Glycolation of Cocaine Esterase Improves In Vivo Residence Time

No small-molecule therapeutic is available to treat cocaine addiction, but enzyme-based therapy to accelerate cocaine hydrolysis in serum has gained momentum. Bacterial cocaine esterase (CocE) is the fastest known native enzyme that hydrolyzes cocaine. However, its lability at 37 C has limited its therapeutic potential. Cross-linking subunits through disulfide bridging is commonly used to stabilize multimeric enzymes. Herein we use structural methods to guide the introduction of two cysteine residues within dimer interface of CocE to facilitate intermolecular disulfide bond formation. The disulfide-crosslinked enzyme displays improved thermostability, particularly when combined with previously described mutations that enhance stability (T172R-G173Q). The newly modified enzyme yielded an extremely stable form of CocE (CCRQ-CocE) that retained greater than 90% of its activity after 41 days at 37 C, representing an improvement of more than 4700-fold over the wild-type enzyme. CCRQ-CocE could also be modified by polyethylene glycol (PEG) polymers, which improved its in vivo residence time from 24 to 72 h, as measured by a cocaine lethality assay, by self-administration in rodents, and by measurement of inhibition of cocaine-induced cardiovascular effects in rhesus monkeys. PEG-CCRQ elicited negligible immune response in rodents. Subunit stabilization and PEGylation has thus produced a potential protein therapeutic with markedly higher stability both in vitro and in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson’s disease

Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson’s disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973–2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation.

59 BASIC BIOLOGICAL SCIENCES↗