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Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system’s actual motor output – the activation of muscle fibers by motor neurons – typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices (‘Myomatrix arrays’) that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a ‘motor unit,’ during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system’s motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system.

Culturally relevant interventions have the potential to improve adolescent health and protective factors associated with sexual risk taking. We evaluated the impact of the Native STAND curriculum with American Indian and Alaska Native (AI/AN or Native) high school students living across the U.S. using a pre-post evaluation design. Native STAND is a comprehensive sexual health curriculum for Native high school students that focuses on sexually transmitted infections, HIV/AIDS, and teen pregnancy prevention, while also covering drug and alcohol use, suicide, and dating violence. The curriculum was implemented in 48 AI/AN communities from 2014 to 2019. A significantly higher percentage of youth reported at post-test having a serious conversation about sex with their friends (post 36% vs. pre 28%, p < 0.001), thinking about lessons learned (post 24% vs. pre 7%, p < 0.0001), and sharing lessons learned during the conversation (post 21% vs. pre 4%, p < 0.001). A lower percentage of AI/AN youth reported being bullied in the last year (post 31% vs. pre 37%, p < 0.001). Family social support was moderated by dose, with subscale scores of 3.75 at post-with p = 0.02). The results demonstrate the effectiveness of Native STAND when delivered in a variety of settings. Efforts are now underway to update Native STAND for medical accuracy, improve alignment with typical class periods, and promote its use and an effective EBI for AI/AN youth.

Abstract Humans exhibit changes in postural control when confronted with threats to stability. This study used a prolonged threat exposure protocol to manipulate emotional state within a threatening context to determine if any threat-induced standing behaviours are employed independent of emotional state. Retention of balance adaptations was also explored. Thirty-seven adults completed a series of 90-s standing trials at two surface heights (LOW: 0.8 m above ground, away from edge; HIGH: 3.2 m above ground, at edge) on two visits 2–4 weeks apart. Psychological and autonomic state was assessed using self-report and electrodermal measures. Balance control was assessed using centre of pressure (COP) and lower limb electromyographic recordings. Upon initial threat exposure, individuals leaned backward, reduced low-frequency centre of pressure (COP) power, and increased high-frequency COP power and plantar/dorsiflexor coactivation. Following repeated exposure, the psychological and autonomic response to threat was substantially reduced, yet only high-frequency COP power and plantar/dorsiflexor coactivation habituated. Upon re-exposure after 2–4 weeks, there was partial recovery of the emotional response to threat and few standing balance adaptations were retained. This study suggests that some threat-induced standing behaviours are coupled with the psychological and autonomic state changes induced by threat, while others may reflect context-appropriate adaptations resistant to habituation.

Spinal interneurons play a critical role in motor output. A given interneuron may receive convergent input from several different sensory modalities and descending centers and relay this information to just as many targets. Therefore, there is a critical need to quantify populations of spinal interneurons simultaneously. Here, we quantify the functional connectivity of spinal neurons through the concurrent recording of populations of lumbar interneurons and hindlimb motor units in the in vivo cat model during activation of either the ipsilateral sural nerve or contralateral tibial nerve. Two microelectrode arrays were placed into lamina VII, one at L3 and a second at L6/7, while an electrode array was placed on the surface of the exposed muscle. Stimulation of tibial and sural nerves elicited similar changes in the discharge rate of both interneurons and motor units. However, these same neurons showed highly significant differences in prevalence and magnitude of correlated activity underlying these two forms of afferent drive. Activation of the ipsilateral sural nerve resulted in highly correlated activity, particularly at the caudal array. In contrast, the contralateral tibial nerve resulted in less, but more widespread correlated activity at both arrays. These data suggest that the ipsilateral sural nerve has dense projections onto caudal lumbar spinal neurons, while contralateral tibial nerve has a sparse pattern of projections.

American Indian and Alaska Native (AI/AN) youth are strong in culture and rich in heritage and experience unique strengths and challenges throughout adolescence. Documenting conditions that protect against risk factors associated with poor health outcomes are needed. We explored scales that measure self-esteem, culture, social support, and community from a sample of 1,456 youth involved in Native STAND, a culturally-relevant evidence-based sexual health intervention. We established content validity by reviewing existing literature and community feedback. Construct validity was examined using factor analysis. The final self-esteem model included seven items, factor loadings ranged from 0.47 to 0.63 for positive self-esteem and 0.77 to 0.81 for negative self-esteem. The final culture model included three items, factor loadings 0.73 to 0.89. The social support scale included four items, factor loadings ranged from 0.86 to 0.87 for family social support and 0.75 to 0.77 for friends social support. The community and community safety scale included three items; factor loadings ranged from 0.52 to 0.82. Coefficient alphas for scales ranged from α = 0.63 to α = 0.86. This study validated scales in a national sample of AI/AN youth-psychometric scales provide an essential tool for documenting the needs and strengths of AI/AN youth.

The Native American Research Centers for Health program was designed to foster research training and skill development for American Indian/Alaska Native trainees. Increasing the number of American Indian/Alaska Native researchers with advanced training in science is one strategy to help decrease health disparities in native peoples. Our NARCH program provided financial support and mentorship for professional and academic development of American Indian/Alaska Native award recipients. We report on an assessment of our NARCH training program that is directed toward increasing the number of qualified American Indian/Alaska Native researchers.

Abstract Height-induced postural threat influences standing balance control. However, it is unknown if minimizing individuals’ emotional response to threat moderates this relationship. This study repeatedly exposed individuals to height-induced postural threat to determine if reducing the emotional response to threat influences standing balance control. Sixty-eight young adults completed a series of standing trials at LOW (0.8 m above ground, away from edge) and HIGH (3.2 m above ground, at edge) postural threat conditions. Emotional state was assessed using self-report and electrodermal measures. Standing balance was assessed through analysis of centre of pressure (COP) movement and lower leg electromyographic activity. Individuals’ emotional response to threat was attenuated following repeated threat exposure. However, threat-induced changes in standing balance were largely preserved. When initially threatened, individuals leaned backward and demonstrated smaller amplitude and higher frequency of COP adjustments; these balance outcomes did not change following repeated threat exposure. Only high frequency COP oscillations (>1.8 Hz) and ankle muscle co-contraction showed any adaptation; regression analyses showed that these behavioural adaptations were accounted for by a combination of emotional and cognitive state changes. This suggests that some threat-induced standing balance changes are more closely linked with the emotional response to threat than others, and are therefore amendable to intervention.

Background/purposePublic health and medical studies in American Indian / Alaska Native (AI/AN) populations have not commonly included AI/AN researchers in principal roles. This leadership disparity may be attributed, in part, to the low numbers of AI/AN researchers who have sufficient training and leadership experience to plan and conduct epidemiologic and health research studies. Under Indian Health Service and National Institutes of Health funding, we have planned and implemented a three-week intensive training program aimed at increasing biomedical research skills among AI/AN health professional and students. We offer a core series of courses to provide fundamental training in research that is needed by all biomedical researchers. Our courses include a large portion of AI/AN faculty in key teaching and mentorship roles. Furthermore we offer a diverse set of health research courses each year. Course offerings are modified year to year. Sixty-seven (67) trainees participated in the 2008 Summer Institute. The paper describes the evaluation of the outcomes and impact the Summer Institute had on the 2008 cohort of students.MethodsWe assessed the experience of the training program at the time it occurred through course evaluations (n=186), while the outcomes evaluation focused on utility of the knowledge gained six months after participating in the training program (n=49). The impact evaluation also focused on the benefit of the Summer Institute training experience in the workplace environment.Results/outcomesOverall, the evaluation suggests that graduates were quite positive in their assessments of the training program and their ability to utilize the newly gained knowledge and skills in the workplace or in their academic pursuits. Supervisors confirmed that graduates had grown from their learning experiences at the Summer Institute training and this growth was having a positive impact on their organization.

In the United States, there is no reliable data to describe the prevalence of eye diseases leading to visual impairment and little active surveillance to address this knowledge gap. Data that is readily available from many state blind registries may provide helpful information on trends and causes of blindness. We analyzed new registrations with the Oregon Commission for the Blind (OCB) and Oregon State Department of Administrative Services (DAS) from 1961 to 2016 for causes of and trends in blindness. Persons with blindness self-refer into the OCB registry and the Oregon State Department of Administrative Services (DAS) includes those receiving social security disability financial support and other state services. Data for 9,273 blind persons registered were analyzed. The most frequent causes of blindness were age related macular degeneration (AMD) 3,308 (38%), followed by diabetic retinopathy (DR) 729 (8%), congenital conditions 697 (8%), optic nerve atrophy 611 (7%), glaucoma 549 (6%), retinitis pigmentosa 546 (6%), retinopathy of prematurity192 (2%), cataract 180 (2%), and trauma 174 (2%). The mean age of onset of blindness was younger for Blacks (31 years) and Hispanics (33 years) than for Whites (44 years). Analysis of state-based registries can provide useful and locally relevant vision and eye health data where little information is otherwise available.

Purpose: Barriers to health care present complex challenges to improving eye health in the U.S., yet few studies have quantitatively measured the impact of these barriers. This study investigated the time elapsed since a person’s most recent eye examination (TLEE) as a measure of barriers to eye care. Methods: Participants (N = 1699) from mobile clinic vision health screenings completed demographic and subjective visual function questionnaires, and then underwent comprehensive eye exams. Associations between demographics, subjective visual function, and visual acuity were analyzed with respect to TLEE. Results: Many Hispanic (34.9%) and uninsured (28.6%) participants had no previous eye exam. Although most Caucasians had a previous eye exam, 40.2% did not have an exam in the previous four years. The majority of participants with diabetes were non-compliant with recommendations of annual eye examinations. Conclusion: These results describe barriers that are specific to subpopulations, providing useful information for efforts to improve eye care access.

In the U.S., the prevalence of blindness is expected to double by 2050 and as many half of those with blinding eye disease are unaware of their diagnosis. Screening for vision health in the community setting may offer a key strategy to address the rising trend avoidable vision loss. However, problems with excessive referrals and low compliance with these referrals (often

The article evaluates the efficacy of topical oxygen therapy (TOT) on dermal wound healing in horses. It mentions that an experimental wound model was created by making an standardized dermal wound on each limb of four healthy horses, fitting an oxygen concentrator device of two limbs leaving two control groups. It concludes that TOT shows little effect on dermal wound healing in healthy horses.

Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this ‘modular assembly’ approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 ‘three-finger’ ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r = 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, Kd values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r = 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here.

Zinc Finger Targeter (ZiFiT) is a simple and intuitive web-based tool that facilitates the design of zinc finger proteins (ZFPs) that can bind to specific DNA sequences. The current version of ZiFiT is based on a widely employed method of ZFP design, the ‘modular assembly’ approach, in which pre-existing individual zinc fingers are linked together to recognize desired target DNA sequences. Several research groups have described experimentally characterized zinc finger modules that bind many of the 64 possible DNA triplets. ZiFiT leverages the combined capabilities of three of the largest and best characterized module archives by enabling users to select fingers from any of these sets. ZiFiT searches a query DNA sequence for target sites for which a ZFP can be designed using modules available in one or more of the three archives. In addition, ZiFiT output facilitates identification of specific zinc finger modules that are publicly available from the Zinc Finger Consortium. ZiFiT is freely available at http://bindr.gdcb.iastate.edu/ZiFiT/.

Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this 'modular assembly' approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 'three-finger' ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r = 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, K(d) values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r = 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here.

Telomerase is a ribonucleoprotein enzyme that adds telomeric DNA repeat sequences to the ends of linear chromosomes. The enzyme plays pivotal roles in cellular senescence and aging, and because it provides a telomere maintenance mechanism for approximately 90% of human cancers, it is a promising target for cancer therapy. Despite its importance, a high-resolution structure of the telomerase enzyme has been elusive, although a crystal structure of an N-terminal domain (TEN) of the telomerase reverse transcriptase subunit (TERT) from Tetrahymena has been reported. In this study, we used a comparative strategy, in which sequence-based machine learning approaches were integrated with computational structural modeling, to explore the potential conservation of structural and functional features of TERT in phylogenetically diverse species. We generated structural models of the N-terminal domains from human and yeast TERT using a combination of threading and homology modeling with the Tetrahymena TEN structure as a template. Comparative analysis of predicted and experimentally verified DNA and RNA binding residues, in the context of these structures, revealed significant similarities in nucleic acid binding surfaces of Tetrahymena and human TEN domains. In addition, the combined evidence from machine learning and structural modeling identified several specific amino acids that are likely to play a role in binding DNA or RNA, but for which no experimental evidence is currently available.