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At least 523 records · Page 29

Understanding the Effects of Long-duration Space Flight on Astronant Functional Task Performance

Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These physiological changes cause balance, gait and visual disturbances, cardiovascular deconditioning, and loss of muscle mass and strength. These changes may affect a crewmember's ability to perform critical mission tasks immediately after landing on a planetary surface. To understand how changes in physiological function affect functional performance, an interdisciplinary pre- and postflight testing regimen, Functional Task Test (FTT), was developed to systematically evaluate both astronaut functional performance and related physiological changes. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We are currently conducting the FTT study on International Space Station (ISS) crewmembers before and after 6-month expeditions. Additionally, in a corresponding study we are using the FTT protocol on subjects before and after 70 days of 6deg head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. Therefore, the bed rest analog allows us to investigate the impact of body unloading on both functional tasks and on the underlying physiological factors that lead to decrement in performance and then compare them with the results obtained in our space flight study. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures included assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, heart rate, blood pressure, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. ISS crewmembers were tested three times before flight, and on 1, 6, and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6, and 12 days after reambulation.

Bloomberg, Jacob J.↗

Understanding the Effects of Spaceflight on Head-trunk Coordination During Walking and Obstacle Avoidance

Prolonged exposure to spaceflight conditions results in a battery of physiological changes, some of which contribute to sensorimotor and neurovestibular deficits. Upon return to Earth, functional performance changes are tested using the Functional Task Test (FTT), which includes an obstacle course to observe post-flight balance and postural stability, specifically during turning. The goal of this study was to quantify changes in movement strategies during turning events by observing the latency between head-and-trunk coordinated movements. It was hypothesized that subjects experiencing neurovestibular adaptations would exhibit head-to-trunk locking ('en bloc' movement) during turning, exhibited by a decrease in latency between head and trunk movement. FTT data samples were collected from 13 ISS astronauts and 26 male 70-day head down tilt bed rest subjects, including bed rest controls (10 BRC) and bed rest exercisers (16 BRE). Samples were analyzed three times pre-exposure, immediately post-exposure (0 or 1 day post) and 2-to-3 times during recovery from the unloading environment. Two 3D inertial measurements units (XSens MTx) were attached to subjects, one on the head and one on the upper back. This study focused primarily on the yaw movements about the subject's center of rotation. Time differences (latency) between head and trunk movement were averaged across a slalom obstacle portion, consisting of three turns (approximately three 60⁰ turns). All participants were grouped as 'decreaser' or 'increaser,' relating to their change in head-to-trunk movement latency between pre- and post- environmental adaptation measures. Space flight unloading (ISS) showed a bimodal response between the 'increaser' and 'decreaser' group, while both bed rest control (BRC) and bed rest exercise (BRE) populations showed increased preference towards a 'decreaser' categorization, displaying greater head-trunk locking. It is clear that changes in movement strategies are adopted during exposure to an unloading environment. These results further the understanding of vestibular-somatosensory convergence and support the use of bed rest as an exclusionary model to better understand sensorimotor changes in space flight.

Madansingh, S.↗

Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain

Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.

59 BASIC BIOLOGICAL SCIENCES↗

Automated electroencephalography system and electroencephalographic correlates of space motion sickness, part 2

Sleep pattern alterations were detected in two subjects by electroencephalographic, electrographic, and electromyographic monitoring before, during and after a 28 day bed rest. Standardized criteria were used for data analysis. During the second half of the bed-rest period, sleep latency and stage 3 increased, while total sleep time, stage 2, and REM latency decreased. In addition, during bed rest both subjects showed an increase in the number of REM periods and a slight increase in stage REM amount. No major alterations were seen in the recovery period. Of the alterations found to be associated with bed rest, only one, the increase in stage 3 sleep, was also seen consistently during Skylab. Conversely, none of the postflight changes seen following Skylab were observed during the post-bed-rest recovery period.

Frost, J. D., Jr.↗

Exercise Responses after Inactivity

The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

Convertino, Victor A.↗

Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects

The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.

NASA Discipline Neuroscience↗

Interstitial pH, K(+), lactate, and phosphate determined with MSNA during exercise in humans

The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans (n = 7). Exercise resulted in approximately a threefold (P < 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 +/- 3 beats/min (P < 0.05) and 20 +/- 2 mmHg (P < 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased (P < 0.05) from rest (1.1 +/- 0.1 mM) to exercise (1. 6 +/- 0.2 mM) and were further increased (P < 0.05) during recovery (2.0 +/- 0.2 mM). Dialysate phosphate concentrations were 0.55 +/- 0. 04, 0.71 +/- 0.05, and 0.48 +/- 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate K(+) levels rose rapidly above resting values (4.2 +/- 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate K(+) levels had peaked with an increase (P < 0.05) of 0.6 +/- 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, H(+) concentrations rapidly decreased (P < 0.05) from resting levels (69.4 +/- 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline (P < 0.05) of 16.7 +/- 3.8 nM being achieved after 5 min. During recovery, H(+) concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, K(+), lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial K(+) and phosphate, but not lactate and H(+), may contribute to the stimulation of the exercise pressor reflex.

Non-NASA Center↗

Effect of dynamic exercise on human carotid-cardiac baroreflex latency

We compared the beat-to-beat responses of heart rate (HR) after brief activation of carotid baroreceptors in resting humans with the responses obtained during mild-to-moderate levels of dynamic exercise [25 and 50% of peak O2 uptake (VO2peak)] to investigate the effect of exercise on baroreflex latency. Carotid baroreceptors were activated by a pressure pulse (5 s) of neck suction (NS, -80 Torr) and neck pressure (NP, +40 Torr) during held expiration. At rest the peak change in HR to NS/NP occurred during the first several heartbeats (1st-3rd beat), whereas during mild and moderate exercise peak HR responses occurred near the end of the NS/NP pulse (6th-8th beat). In contrast, time (s) to the peak change in HR was not different between rest and exercise (P > 0.05). Reflex tachycadia to NP progressively decreased during exercise (17 +/- 3, 10 +/- 1, and 4 +/- 1% of control, rest vs. 25% VO2peak, vs. 50% VO2peak, respectively, P < 0.05), and a strong positive correlation was found between the magnitude of the reflex tachycardia and a measure of HR variability (cardiac vagal tone index, r = 0.74, P < 0.0001). Reflex bradycardia to NS gradually increased during exercise (13 +/- 2, 17 +/- 2, and 18 +/- 2% of control, rest vs. 25% VO2peak, vs. 50% VO2peak, respectively, P = 0.10) and was negatively correlated with cardiac vagal tone (r = 0.42, P < 0.06).(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Program Space Physiology and Countermeasures↗

Near-Infrared Spectroscopic Measurement of the Effect of Leg Dominance on Muscle Oxygen Saturation During Cycling

The effect of leg dominance on the symmetry of the biomechanics during cycling remains uncertain -- asymmetries have been observed in kinematics and kinetics, while symmetries were found in muscle activation. No studies have yet investigated the symmetry of muscle metabolism during cycling. Near-infrared spectroscopy (NIRS) provides a non-invasive method to investigate the metabolic responses of specific muscles during cycling. PURPOSE: To determine whether there was an effect of leg dominance on thigh muscle oxygen saturation (SmO2) during incrementally loaded submaximal cycling using NIRS. METHODS: Eight right leg dominant, untrained subjects (5 men, 3 women; 31+/-2 yrs; 168.6+/-1.0 cm; 67.2+/-1.8 kg, mean +/- SE) volunteered to participate. Spectra were collected bilaterally from the vastus lateralis (VL) during supine rest and cycling. SmO2 was calculated using previously published methods. Subjects pedaled at 65 rpm while resistance to pedaling was increased in 0.5 kp increments from 0.5 kp every 3 min until the subject reached 80% of age-predicted maximal heart rate. SmO2 was averaged over 3 min for each completed stage. A two-way ANOVA was performed to test for leg differences. A priori contrasts were used to compare work levels to rest. RESULTS: VL SmO2 was not different between the dominant and non-dominant legs at rest and during exercise (p=0.57). How SmO2 changed with workload was also not different between legs (p=0.32). SmO2 at 0.5 kp (60.3+/-4.0, p=0.12) and 1.0 kp (59.5+/-4.0, p=0.10) was not different from rest (69.1+/-4.0). SmO2 at 1.5 kp (55.4 4.0, p=0.02), 2.0 kp (55.7+/-5.0, p=0.04), and 2.5 kp (43.4+/-7.9, p=0.01) was significantly lower than rest. CONCLUSION: VL SmO2 during cycling is not different between dominant and non-dominant legs and decreases with moderate workload in untrained cyclists. Assuming blood flow is directed equally to both legs, similar levels of oxygen extraction (as indicated by SmO2) suggests the metabolic load of cycling is not different between legs. This is in agreement with a recent study demonstrating symmetrical increase of muscle activation of the VL during cycling. Leg dominance did not influence VL SmO2 during submaximal cycling, but may have an effect at higher loads or during other forms of exercise, such as walking and running.

Ellerby, Gwenn E. C.↗

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion.

Moore, Alan D., Jr.↗

Influence of Exercise Modality on Cerebral-Ocular Hemodynamics and Pressures

Background: Moderate and high intensity aerobic or resistance exercise has clearly identified benefits for cardiac, muscle, and bone health. However, the impact of such exercise - either as a mitigating or an exacerbating factor - on the development of the visual impairment and intracranial pressure syndrome (VIIP) is unknown. Accordingly, our aim was to characterize the effect of an acute bout of resistance (RE), moderate-intensity continuous (CE), and high-intensity interval exercise (IE) during a cephalad fluid shift on cerebral-ocular hemodynamics and pressures. Methods: 10 male subjects (36 plus or minus 9 years) completed 4 testing days in a 15 degree head-down tilt (HDT): (1) assessment of maximum volume of O (sub 2), (2) RE session (4 sets of 12 repetition maximum leg press exercise), (3) CE session (30 minutes of cycling at 60 percent maximum volume of O (sub 2)), and (4) IE session (4 by 4-minute intervals of exercise at 85 percent maximum volume of O (sub 2) with 3-minute active rest periods). During each session, blood flow (Vivid-e, GE Healthcare) in extracranial arteries (common carotid artery, CCA; internal carotid artery, ICA; external carotid artery, ECA and vertebral artery, VA), and mean blood flow velocity in middle cerebral artery (MCA), internal jugular pressure (IJP; VeinPress), and intraocular pressure (IOP; Icare PRO) were measured at rest, at the end of each resistance or interval set, and every 5 minutes during continuous exercise. Translaminar pressure gradient (TLPG) was estimated by subtracting IJP from IOP. Results: There were no differences across days in pre-exercise resting blood flows or pressures. IOP decreased slightly from HDT rest (20.2 plus or minus 2.3 millimeters of mercury) to exercise (RE: 19.2 plus or minus 2.8 millimeters of mercury; CE: 18.9 plus or minus 3.2 millimeters of mercury; IE: 20.1 plus or minus 2.8 millimeters of mercury), while IJP decreased during CE (31.6 plus or minus 9.5 millimeters of mercury) and RE (32.0 plus or minus 8.1 millimeters of mercury), and increased during IE (35.1 plus or minus 9.5 millimeters of mercury) from HDT rest (33.3 plus or minus 6.5 millimeters of mercury). Estimated TLPG was increased during IE only. Compared to RE and CE, IE resulted in the greatest increase in MCA blood flow velocity and extracranial artery blood flow. Conclusions: These preliminary results suggest that high-intensity IE acutely increases cerebral blood flow, IJP, and TLPG. Alterations in TLPG is one mechanism that may contribute to optic nerve sheath edema in astronauts. Accordingly, acutely raising IOP and/or orbital pressure during exercise could optimize cerebral-ocular pressures during spaceflight.

Scott, J.↗

The Functional Task Test: Results from the One-Year Mission

Exposure to the microgravity conditions of spaceflight causes astronauts to experience alterations in multiple physiological systems including sensorimotor disturbances, cardiovascular deconditioning, and loss of muscle mass and strength. Some or all of these changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on a planetary surface. The goal of our recently completed Functional Task Test (FTT) study was to determine the effects of spaceflight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. The FTT is comprised of seven functional tests and a corresponding set of interdisciplinary physiological measures specifically targeting the sensorimotor, cardiovascular and muscular changes associated with exposure to spaceflight. Both Shuttle and International Space Station (ISS) astronauts were tested before and after spaceflight. Additionally, we conducted a supporting study in which subjects performed the FTT protocol before and after 70 days of 6 deg head-down bed rest, an analog for spaceflight. Two groups of bed rest subjects were studied: one group who performed aerobic and resistive exercise during bed rest using protocols similar to astronauts and one group who served as non-exercise controls. The bed rest analog allowed us to isolate the impact of body unloading without other spaceflight environmental factors on both functional tasks and on the underlying physiological factors that lead to decrements in performance, and then to compare those results with the results obtained in our spaceflight study. As an extension to the FTT study we collected data from one ISS crewmember who experienced 340 days in space using the same FTT protocol used previously to test spaceflight and bed rest subjects. Data were collected three times preflight and 1.7, 7.5 and 36.5 days after landing. The FTT one-year results will be presented at the meeting, and a comparison will be made with data previously obtained using the same protocol on astronauts tested before and after 6 months in space. Future work will focus on collecting data from additional subjects from one-year flights to gain a better assessment of extreme long-duration exposure to spaceflight on both functional measure of performance and physiological metrics.

Bloomberg, J. J↗

Focus Group Study of US Pilots on Fatigue in Short-Haul Flight Operations

Introduction: There are few studies investigating the impact of fatigue in short-haul flight operations conducted under United States (US) Federal Aviation Regulations (FAR) Part 117 flight and duty limitations and rest requirements. In order to understand the fatigue factors unique to short-haul operations, we conducted a series of focus groups across four major commercial passenger airlines in the US. The outcomes of this study were intended to inform the scope of a larger study of fatigue in short-haul operations. Methods: Ninety short-haul pilots were recruited through emails distributed by airline safety teams and labor representatives. Fourteen focus groups were conducted via an online conferencing platform in which participants were asked to identify, specific to short-haul: a) schedules and operations that lead to elevated fatigue; b) schedules and operations that are not fatiguing, and c) important fatigue factors to study. Data were collected anonymously and coded using conventional qualitative content analysis, with axial coding and summative analysis used to identify main themes and over-arching categories. Results: Participants had an average of 12,348 (6,483) lifetime flying hours with 71 (14.5) hours of monthly flying. Forty-six percent of participants were captains. The six fatigue factor categories identified were: circadian disruption (e.g., circadian switches, redeyes), high workload (e.g., hassle factors, number of flights per duty), inadequate rest opportunity (e.g., minimum rest layovers, quality of rest facilities), schedule changes (e.g., unpredictability), regulation and policy issues (e.g., scheduling up to FAR 117 limits), and long sits (e.g., long wait times between flights). Discussion: A field study informed by these results and designed to investigate the prevalence and impact of these factors in US short-haul operations is currently underway.

aviation↗

The View From the Flight Deck: Pilot Perspectives on Fatigue in Short-Haul Operations

INTRODUCTION: There are few studies investigating the impact of fatigue in short-haul flight operations conducted under United States (US) Federal Aviation Regulations (FAR) Part 117 flight and duty limitations and rest requirements. In order to understand the fatigue factors unique to short-haul operations, we conducted a series of focus groups across four major commercial passenger airlines in the US. The outcomes of this study were intended to inform the scope of a larger study of fatigue in short-haul operations. METHODS: Ninety short-haul pilots were recruited through emails distributed by airline safety teams and labor representatives. Fourteen focus groups were conducted via an online conferencing platform in which participants were asked to identify, specific to short-haul: a) schedules and operations that lead to elevated fatigue; b) schedules and operations that are not fatiguing, and c) important fatigue factors to study. Data were collected anonymously and coded using conventional qualitative content analysis, with axial coding and summative analysis used to identify main themes and over-arching categories. RESULTS: Participants had an average of 12,348 (6,483) lifetime flying hours with 71 (14.5) hours of monthly flying. Forty-six percent of participants were captains. The six fatigue factor categories identified were: circadian disruption (e.g., circadian switches, redeyes), high workload (e.g., hassle factors, number of flights per duty), inadequate rest opportunity (e.g., minimum rest layovers, quality of rest facilities), schedule changes (e.g., unpredictability), regulation and policy issues (e.g., scheduling up to FAR 117 limits), and long sits (e.g., long wait times between flights). DISCUSSION: A field study informed by these results and designed to investigate the prevalence and impact of these factors in US short-haul operations is currently underway.

aviation↗

Performance Comparisons for Artificially Propagated and Wild Pacific Lamprey Juveniles and Larvae

ABSTRACT Artificially propagated Pacific lamprey ( Entosphenus tridentatus ) are produced for restoration and for use in dam passage studies to reduce the demand for wild fish. Such uses require that animals are representative of their wild counterparts. Previous work indicated that this is true for Pacific lamprey larvae and juveniles reared in the hatchery with respect to the length of sustained swimming. However, more subtle differences in behaviour and performance that lamprey need to survive have not been assessed. In this study, artificially propagated and wild fish were compared in laboratory tests under no‐flow conditions to examine light avoidance, burrowing speed, burst swim speed, volitional routine swim speed and time to come to rest. Most larvae burrowed in less than a minute, and we found highly significant differences ( p < 0.001) between artificially propagated and wild larvae burrowing times, a critical escape behaviour. This could have implications for studies of larval entrainment at irrigation diversion canals or in turbine boils at dams. Interestingly, all of the wild juveniles tested came to rest quickly after introduction to the chamber (1.5 min), while artificially propagated lamprey swam robotically near the surface and 48% did not come to rest in the first 10 min (median time to rest = 9.5 min). In contrast, wild juveniles quickly (median = 1.47 min) sought areas near the tank bottom and attached strongly with their oral disc. Such behavioural differences could have important survival consequences for artificially propagated lamprey as they approach turbine intakes, bypass screens and irrigation diversion headgates. This study highlights the need to conduct behavioural assays that examine subtleties of fish behaviour that can be missed with traditional swim tunnel comparisons.

Frick, Kinsey [Fish Ecology Division, Northwest Fi↗

Global brain activity and its coupling with cerebrospinal fluid flow is related to tau pathology

Abstract INTRODUCTION Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting‐state functional magnetic resonance imaging (rsfMRI). METHODS Low‐frequency (< 0.1 Hz) resting‐state global brain activity is coupled with CSF flow and potentially reflects CSF dynamics‐related clearance. We examined the correlation between rsfMRI measures of CSF inflow and global activity (gBOLD–CSF coupling) as a predictor, interacting with amyloid beta (Aβ), of tau and cortical thickness (dependent variables) across Alzheimer's Disease Neuroimaging Initiative (ADNI) participants from cognitively unimpaired through mild cognitive impairment (MCI) and Alzheimer's disease (AD). RESULTS Tau deposition in Aβ+ participants, accompanied by cortical thinning and cognitive decline, is associated with decreased gBOLD–CSF coupling. Tau mediates the relationship between coupling and thickness. DISCUSSION Findings suggest that resting‐state global brain activity and CSF movements comodulate Alzheimer's tau deposition, presumably related to CSF clearance. Highlights A non‐invasive functional magnetic resonance imaging (fMRI) assessment of a CSF clearance‐related process is carried out. Global brain activity is coupled with CSF inflow in human fMRI during resting state. Global fMRI–CSF coupling is correlated with tau in Alzheimer's disease (AD). This coupling measure is also associated with cortical thickness, mediated by tau.

Neurosciences & Neurology↗

Nonaxisymmetric Shapes of Biological Membranes from Locally Induced Curvature

In various biological processes such as endocytosis and caveolae formation, the cell membrane is locally deformed into curved morphologies. Previous models to study membrane morphologies resulting from locally induced curvature often only consider the possibility of axisymmetric shapes-an indeed unphysical constraint. Past studies predict that the cell membrane buds at low resting tensions and stalls at a flat pit at high resting tensions. In this work, we lift the restriction to axisymmetry to study all possible membrane morphologies. Only if the resting tension of the membrane is low, we reproduce axisymmetric membrane morphologies. When the resting tension is moderate to high, we show that 1) axisymmetric membrane pits are unstable and 2) nonaxisymmetric ridge-shaped structures are energetically favorable. Furthermore, we find the interplay between intramembrane viscous flow and the rate of induced curvature affects the membrane's ability to transition into nonaxisymmetric ridges and axisymmetric buds. In particular, we show that axisymmetric buds are favored when the induced curvature is rapidly increased, whereas nonaxisymmetric ridges are favored when the curvature is slowly increased. Overall, our results hold relevant implications for biological processes such as endocytosis and physical phenomena like phase separation in lipid bilayers.

59 BASIC BIOLOGICAL SCIENCES↗

H-cluster Intermediates and Catalytic Properties of Clostridium pasteurianum [FeFe]-Hydrogenase III

[FeFe]-Hydrogenases are structurally diverse enzymes that catalyze reversible H2 activation at a catalytic cofactor or H-cluster. The H-cluster is a [4Fe-4S] cubane linked by a cysteine thiolate to a diiron subsite containing unique CO, CN-, and dithiomethylamine ligands. The established H-cluster resting state of [4Fe-4S]2+-[FeII-FeI], or Hox, functions in H2 binding and oxidation, or by proton-coupled reduction initiates H2 evolution. In contrast, in Clostridium pasteurianum [FeFe]-hydrogenase III (CpIII) the resting state of the H-cluster is fully oxidized, [4Fe-4S]2+-[FeII-FeII], or Hox+1. To begin to understand if Hox+1 has a role in the mechanism of CpIII, we determined the spectroscopic and redox properties of CpIII H-cluster states under catalytic conditions. CpIII poised in Hox+1 and either equilibrated under 1 atm of H2 or reduced with sodium dithionite, resulted in a mixture of reduced states including Hox (Em8 = -407 mV), Htrans-like [4Fe-4S]+-[FeII-FeII] (Em8 = -418 mV), Hred [4Fe-4S]+-[FeII-FeI], and HredH+ [4Fe-4S]2+-[FeI-FeI] (Em8 = -455-480 mV). Under H2 the population of the Htrans-like state was >20-fold higher than Hox, implicating a role in CpIII catalysis. Unlike other enzymes, there was no spectral evidence of fully reduced states, such as HsredH+ ([4Fe-4S]+-[FeI-FeI]) or Hhyd ([4Fe-4S]+-[FeII-FeII]-H-). Thus, while the H-cluster states of CpIII encompass most of the catalytic intermediates, it is either unable to form HsredH+ and Hhyd, or these states are highly destabilized in CpIII. Thus, these results demonstrate that catalytic intermediates of reduced CpIII differ from the typical intermediates of other catalytic [FeFe]-hydrogenases and may explain the catalytic preference for H2 production.

08 HYDROGEN↗