Functional Lower Extremity Strength Influences Stepping Strategy in Community-Dwelling Older Adults During Single and Dual-Task Walking.

As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies. However, the link between functional lower extremity strength and stepping strategy is unknown. Therefore, understanding how age-related reductions in functional lower extremity strength influence stepping strategy is vital to unraveling mobility limitations. Participants were recruited and tested at a local community event, where they were outfitted with IMUs and walked across a pressurized walkway. Our study reveals that older adults with normal strength prefer adjusting their step time during walking tasks, while those with reduced strength do not exhibit a preferred stepping strategy. This study provides valuable insights into the influence of functional lower extremity strength on stepping strategy in community-dwelling older adults during simple and complex walking tasks. These findings could aid in diagnosing gait deviations and developing appropriate treatment or management plans for mobility disability in older adults.

Effects of Stroboscopic Vision on Depth Jump Motor Control: A Biomechanical Analysis.

Researchers commonly use the 'free-fall' paradigm to investigate motor control during landing impacts, particularly in drop landings and depth jumps (DJ). While recent studies have focused on the impact of vision on landing motor control, previous research fully removed continuous visual input, limiting ecological validity. The aim of this investigation was to evaluate the effects of stroboscopic vision on depth jump (DJ) motor control. Ground reaction forces (GRF) and lower-extremity surface electromyography (EMG) were collected for 20 young adults (11 male; 9 female) performing six depth jumps (0.51 m drop height) in each of two visual conditions (full vision vs. 3 Hz stroboscopic vision). Muscle activation magnitude was estimated from EMG signals using root-mean-square amplitudes (RMS) over specific time intervals (150 ms pre-impact; 30-60 ms, 60-85 ms, and 85-120 ms post-impact). The main effects of and interactions between vision and trial number were assessed using two-way within-subjects repeated measures analyses of variance. Peak GRF was 6.4% greater, on average, for DJs performed with stroboscopic vision compared to full vision (p = 0.042). Tibialis anterior RMS EMG during the 60-85 ms post-impact time interval was 14.1% lower for DJs performed with stroboscopic vision (p = 0.020). Vastus lateralis RMS EMG during the 85-120 ms post-impact time interval was 11.8% lower for DJs performed with stroboscopic vision (p = 0.017). Stroboscopic vision altered DJ landing mechanics and lower-extremity muscle activation. The observed increase in peak GRF and reduction in RMS EMG of the tibialis anterior and vastus lateralis post-landing may signify a higher magnitude of lower-extremity musculotendinous stiffness developed pre-landing. The results indicate measurable sensorimotor disruption for DJs performed with stroboscopic vision, warranting further research and supporting the potential use of stroboscopic vision as a sensorimotor training aid in exercise and rehabilitation. Stroboscopic vision could induce beneficial adaptations in multisensory integration, applicable to restoring sensorimotor function after injury and preventing injuries in populations experiencing landing impacts at night (e.g., military personnel).

Incline and decline running alters joint moment contributions but not peak support moments in individuals with an anterior cruciate ligament reconstruction and controls.

Individuals with an anterior cruciate ligament reconstruction (ACLR) commonly exhibit altered gait patterns, potentially contributing to an increased risk of osteoarthritis (OA). Joint moment contributions (JMCs) and support moments during incline and decline running are unknown in healthy young adults and individuals with an ACLR. Understanding these conditional joint-level changes could explain the increased incidence of OA that develops in the long term. Therefore, this knowledge may provide insight into the rehabilitation and prevention of OA development. We aimed to identify the interlimb and between-group differences in peak support moments and subsequent peak ankle, knee, and hip JMCs between individuals with an ACLR and matched controls during different sloped running conditions. A total of 17 individuals with unilateral ACLR and 17 healthy individuals who were matched based on sex, height, and mass participated in this study. The participants ran on an instrumented treadmill at an incline of 4°, decline of 4°, incline of 10°, and decline of 10°. The last 10 strides of each condition were used to compare the whole-stance phase support moments and JMCs between limbs, ACLR, and control groups and across conditions. No differences in JMCs were identified between limbs or between the ACLR and healthy control groups across all conditions. Support moments did not change among the different sloped conditions, but JMCs significantly changed. Specifically, ankle and knee JMCs decreased and increased by 30% and 33% from an incline of 10° to a decline of 10° running. Here, the lower extremities can redistribute mechanics across the ankle, knee, and hip while maintaining consistent support moments during incline and decline running. Our data provide evidence that those with an ACLR do not exhibit significant alterations in joint contributions while running on sloped conditions compared to the matched controls. Our findings inform future research interested in understanding the relationship between sloped running mechanics and the incidence of deleterious acute or chronic problems in people with an ACLR.

Characterization of initial ankle-foot prosthesis prescription patterns in U.S. Service members following unilateral transtibial amputation.

Introduction: The purpose of this study was to explore relationships between patient-specific characteristics and initial ankle-foot prosthesis prescription patterns among U.S. Service members with unilateral transtibial limb loss. Methods: A retrospective review of health records identified 174 individuals with unilateral transtibial limb loss who received care at Walter Reed National Military Medical Center between 2001 and 2019. We examined patient-specific factors such as demographics, participant duty status at injury and amputation, amputation etiology, and timing between injury, amputation, and initial prescription. The type of first prescribed ankle-foot prosthesis was categorized as energy storing and return - nonarticulating, energy storing and return - articulating, or computer controlled. Results: Sex, amputation etiology, time from injury to initial prescription, and time from amputation to initial prescription differed by type of initial ankle-foot prosthesis prescription. Service members with shorter intervals between injury-initial prescription and amputation-initial prescription, and those injured by combat blast, were more likely to receive a non-articulating device. Incorporating sex, time from injury-initial prescription, time from amputation-initial prescription, and amputation etiology as predictors of prosthesis type, we were able to correctly classify 72% of all first prostheses prescribed. Discussion: Patient-specific characteristics such as sex, the time between injury-initial prescription, time from amputation-initial prescription and amputation etiology are essential characteristics that influence initial ankle-foot prosthesis prescription patterns in U.S. Service members.

Step edge highlighters and illuminance changes influence stair descent in a real-world setting.

Studies investigating the effect of tread edge highlighters on descent speed differ, but collectively report the potential benefit of reduced fall risk. Here we examine the impact of adding high-contrast black vinyl striping to the front edge of each step's tread and its impact on descending gait speed (intervention), while controlling for illumination. Descending gait speed was estimated from 5,824 video observations using the stairway length and entry and exit times. A second stairway was unaltered (control) to compare to the intervention. Stair users were primarily 18-30 years old with a small percentage being middle-aged and older adults. Descending gait speed was significantly slower on the intervention stairway (Linear mixed effects model: standardised coefficient = -0.07, 95% CI = [-0.12, -0.02], p = .010) compared to the control and may be impacted by illuminance. We propose that the slowed gait speed could be due to changes in gait kinematics (e.g. foot clearance) and may reduce fall-risk. Practitioner summary: Tread-edge contrast enhancement could be a low-cost means to reduce fall-risk on stairways, but its impact on gait kinematics is not well understood. We found that contrast enhancement reduced descending gait speed, but descending gait speed's impact on fall risk reduction ultimately requires further investigation.

Safe stairway negotiation: Role of distractions and handrail use.

INTRODUCTION: This study sought to examine stairway safety by identifying associations between fall-related events on stairways, distractions, gait speed, drifting, as well as handrail use and proximity. METHOD: Video recordings captured 11,137 observations of stair users in two public stairways and recorded distractions (e.g., looking at a mobile device, talking on a mobile device, using earbuds or headphones, holding a mobile device, or talking with a peer), gait speed (m/s), drifting (change of direction), as well as handrail use and proximity to a handrail. RESULTS: In our sample, consisting of primarily young adults (observed 18-40 years old), we found that when a distraction was present, gait speed was reduced (p <.001), drifting increased (p <.001), and handrail use negatively impacted (p <.001) compared to stair users who were not distracted. CONCLUSIONS: These results indicate that distractions, such as mobile devices, used during stair negotiation can reduce handrail use and increase behaviors associated with fall-related events. PRACTICAL APPLICATIONS: Mobile device use during stairway negotiation increases the likelihood of distraction-induced events. Stair users should be encouraged to limit or avoid mobile device use in public stairway environments. Mobile manufacturers and mobile app developers could aim to develop strategies or mobile app alerts to reduce the impact of distractions (e.g., mobile device use) during stair negotiation to lessen the health and financial burden associated with fall-related events on stairways.

Calibration to improve forward model simulation of microwave emissivity at GPM frequencies over the U.S. Southern Great Plains.

Better estimation of land surface microwave emissivity promises to improve over-land precipitation retrievals in the GPM era. Forward models of land microwave emissivity are available but have suffered from poor parameter specification and limited testing. Here, forward models are calibrated and the accompanying change in predictive power is evaluated. With inputs (e.g., soil moisture) from the Noah land surface model and applying MODIS LAI data, two microwave emissivity models are tested, the Community Radiative Transfer Model (CRTM) and Community Microwave Emission Model (CMEM). The calibration is conducted with the NASA Land Information System (LIS) parameter estimation subsystem using AMSR-E based emissivity retrievals for the calibration dataset. The extent of agreement between the modeled and retrieved estimates is evaluated using the AMSR-E retrievals for a separate 7-year validation period. Results indicate that calibration can significantly improve the agreement, simulating emissivity with an across-channel average root-mean-square-difference (RMSD) of about 0.013, or about 20% lower than if relying on daily estimates based on climatology. The results also indicate that calibration of the microwave emissivity model alone, as was done in prior studies, results in as much as 12% higher across-channel average RMSD, as compared to joint calibration of the land surface and microwave emissivity models. It remains as future work to assess the extent to which the improvements in emissivity estimation translate into improvements in precipitation retrieval accuracy.

High confidence proteomic analysis of yeast LDs identifies additional droplet proteins and reveals connections to dolichol synthesis and sterol acetylation.

Accurate protein inventories are essential for understanding an organelle's functions. The lipid droplet (LD) is a ubiquitous intracellular organelle with major functions in lipid storage and metabolism. LDs differ from other organelles because they are bounded by a surface monolayer, presenting unique features for protein targeting to LDs. Many proteins of varied functions have been found in purified LD fractions by proteomics. While these studies have become increasingly sensitive, it is often unclear which of the identified proteins are specific to LDs. Here we used protein correlation profiling to identify 35 proteins that specifically enrich with LD fractions of Saccharomyces cerevisiae Of these candidates, 30 fluorophore-tagged proteins localize to LDs by microscopy, including six proteins, several with human orthologs linked to diseases, which we newly identify as LD proteins (Cab5, Rer2, Say1, Tsc10, YKL047W, and YPR147C). Two of these proteins, Say1, a sterol deacetylase, and Rer2, a cis-isoprenyl transferase, are enzymes involved in sterol and polyprenol metabolism, respectively, and we show their activities are present in LD fractions. Our results provide a highly specific list of yeast LD proteins and reveal that the vast majority of these proteins are involved in lipid metabolism.

Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry.

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca(2+) homeostasis.

Building a life sciences innovation ecosystem.

Universities should support research with commercial potential, provide a supportive environment for start-ups, and partner enthusiastically with the private sector.

Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation.

Dolichol monophosphate (Dol-P) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. Dol-P is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood. Here, we identify Nogo-B receptor (NgBR) as an essential component of the Dol-P biosynthetic machinery. Loss of NgBR results in a robust deficit in cis-IPTase activity and Dol-P production, leading to diminished levels of dolichol-linked oligosaccharides and a broad reduction in protein N-glycosylation. NgBR interacts with the previously identified cis-IPTase hCIT, enhances hCIT protein stability, and promotes Dol-P production. Identification of NgBR as a component of the cis-IPTase machinery yields insights into the regulation of dolichol biosynthesis.

Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4-Cav-1-mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.

Extraction of beryllium from refractory beryllium oxide with dilute ammonium bifluoride and determination by fluorescence: a multiparameter performance evaluation.

Beryllium exposure can cause a number of deleterious health effects, including beryllium sensitization and the potentially fatal chronic beryllium disease. Efficient methods for monitoring beryllium contamination in workplaces are valuable to help prevent dangerous exposures to this element. In this work, performance data on the extraction of beryllium from various size fractions of high-fired beryllium oxide (BeO) particles (from < 32 microm up to 212 microm) using dilute aqueous ammonium bifluoride (ABF) solution were obtained under various conditions. Beryllium concentrations were determined by fluorescence using a hydroxybenzoquinoline fluorophore. The effects of ABF concentration and volume, extraction temperature, sample tube types, and presence of filter or wipe media were examined. Three percent ABF extracts beryllium nearly twice as quickly as 1% ABF; extraction solution volume has minimal influence. Elevated temperatures increase the rate of extraction dramatically compared with room temperature extraction. Sample tubes with constricted tips yield poor extraction rates owing to the inability of the extraction medium to access the undissolved particles. The relative rates of extraction of Be from BeO of varying particle sizes were examined. Beryllium from BeO particles in fractions ranging from less than 32 microm up to 212 microm were subjected to various extraction schemes. The smallest BeO particles are extracted more quickly than the largest particles, although at 90 degrees C even the largest BeO particles reach nearly quantitative extraction within 4 hr in 3% ABF. Extraction from mixed cellulosic-ester filters, cellulosic surface-sampling filters, wetted cellulosic dust wipes, and cotton gloves yielded 90% or greater recoveries. Scanning electron microscopy of BeO particles, including partially dissolved particles, shows that dissolution in dilute ABF occurs not just on the exterior surface but also via accessing particles' interiors due to porosity of the BeO material. Comparison of dissolution kinetics data shows that as particle diameter approximately doubles, extraction time is increased by a factor of about 1.5, which is consistent with the influence of porosity on dissolution.

Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking.

The Nogo-B receptor (NgBR) is a recently identified receptor for the N terminus of reticulon 4B/Nogo-B. Other than its role in binding Nogo-B, little is known about the biology of NgBR. To elucidate a basic cellular role for NgBR, we performed a yeast two-hybrid screen for interacting proteins, using the C-terminal domain as bait, and identified Niemann-Pick type C2 protein (NPC2) as an NgBR-interacting protein. NPC2 protein levels are increased in the presence of NgBR, and NgBR enhances NPC2 protein stability. NgBR localizes primarily to the endoplasmic reticulum (ER) and regulates the stability of nascent NPC2. RNAi-mediated disruption of NgBR or genetic deficiency in NgBR lead to a decrease in NPC2 levels, increased intracellular cholesterol accumulation, and a loss of sterol sensing, all hallmarks of an NPC2 mutation. These data identify NgBR as an NPC2-interacting protein and provide evidence of a role for NgBR in intracellular cholesterol trafficking.

The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo.

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) and increased production of HIF-1alpha-responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling.

Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis.

Posttranscriptional gene regulation by microRNAs (miRNAs) is important for many aspects of development, homeostasis, and disease. Here, we show that reduction of endothelial miRNAs by cell-specific inactivation of Dicer, the terminal endonuclease responsible for the generation of miRNAs, reduces postnatal angiogenic response to a variety of stimuli, including exogenous VEGF, tumors, limb ischemia, and wound healing. Furthermore, VEGF regulated the expression of several miRNAs, including the up-regulation of components of the c-Myc oncogenic cluster miR-17-92. Transfection of endothelial cells with components of the miR-17-92 cluster, induced by VEGF treatment, rescued the induced expression of thrombospondin-1 and the defect in endothelial cell proliferation and morphogenesis initiated by the loss of Dicer. Thus, endothelial miRNAs regulate postnatal angiogenesis and VEGF induces the expression of miRNAs implicated in the regulation of an integrated angiogenic response.

Approaches for studying angiogenesis-related signal transduction.

Understanding how extracellular growth factors activate intracellular pathways that promote angiogenesis is a broad area of research. In this chapter, we outline the systematic dissection of vascular endothelial growth factor (VEGF)-mediated activation of endothelial nitric oxide synthase and other downstream targets that are relevant to the angiogenic response. These approaches may also be applied to most other angiogenic-factor signaling cascades.

Estimating net changes in life-cycle emissions from adoption of emerging civil infrastructure technologies.

There is a net emissions change when adopting new materials for use in civil infrastructure design. To evaluate the total net emissions change, one must consider changes in manufacture and associated life-cycle emissions, as well as changes in the quantity of material required. In addition, in principle one should also consider any differences in costs of the two designs because cost savings can be applied to other economic activities with associated environmental impacts. In this paper, a method is presented that combines these considerations to permit an evaluation of the net change in emissions when considering the adoption of emerging technologies/materials for civil infrastructure. The method factors in data on differences between a standard and new material for civil infrastructure, material requirements as specified in designs using both materials, and price information. The life-cycle assessment approach known as economic input-output life-cycle assessment (EIO-LCA) is utilized. A brief background on EIO-LCA is provided because its use is central to the method. The methodology is demonstrated with analysis of a switch from carbon steel to high-performance steel in military bridge design. The results are compared with a simplistic analysis that accounts for the weight reduction afforded by use of the high-performance steel but assuming no differences in manufacture.

Dominant-negative Hsp90 reduces VEGF-stimulated nitric oxide release and migration in endothelial cells.

OBJECTIVE: Heat-shock protein 90 (Hsp90) coordinates the regulation of diverse signaling proteins. We try to develop a new tool to explore the regulatory functions of Hsp90 in endothelial cells (ECs) instead of the existing chemical approaches. METHODS AND RESULTS: We designed a dominant-negative Hsp90 construct by site-direct mutagenesis of residue Asp-88 to Asn (D88N-Hsp90) based on the structure of the ATP/ADP-binding site. Recombinant wild-type Hsp90 protein binds ATP-Sepharose beads in manner inhibited by ATP or 17-AAG, a specific inhibitor for Hsp90, however the binding activity of D88N-Hsp90 was markedly reduced and the inhibitory effects of ATP or 17-AAG were negligible. The dimerization between endogenous Hsp90alpha and exogenous HA-Hsp90beta was confirmed by immunoprecipitation, however the association between eNOS and D88N-Hsp90 was less than WT-Hsp90. Furthermore, adenoviral transduction of bovine aortic ECs with D88N-Hsp90 suppressed VEGF-induced phosphorylation of Akt, eNOS, and NO release and the inhibitory effect was blocked by okadaic acid. Moreover, D88N-Hsp90 abolished VEGF-stimulated Rac activation and suppressed VEGF-induced stress fiber formation. Transduction with D88N-Hsp90 decreased growth medium mediated migration of wild-type ECs, but not Akt1(-/-) ECs suggesting that Akt is key target of Hsp90. CONCLUSIONS: Our data demonstrate that dominant-negative Hsp90 modulates endothelial cell mobility mainly through PP2A-mediated dephosphorylation of Akt and Rac activation.

Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells.

Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates vascular function is unknown. Here, we identify a previously uncharacterized Nogo-B receptor specific for the amino terminus of Nogo-B and show that Nogo-B receptor localizes with the ligand Nogo-B during VEGF and wound healing angiogenesis in vivo, mediates chemotaxis in a heterologous expression system and chemotaxis, and 3D tube formation in native endothelial cells. Thus, identification of this receptor may lead to the discovery of agonists or antagonists of this pathway to regulate vascular remodeling and angiogenesis.