Lhx3/4 initiates a cardiopharyngeal-specific transcriptional program in response to widespread FGF signaling.

Individual signaling pathways, such as fibroblast growth factors (FGFs), can regulate a plethora of inductive events. According to current paradigms, signal-dependent transcription factors (TFs), such as FGF/MapK-activated Ets family factors, partner with lineage-determining factors to achieve regulatory specificity. However, many aspects of this model have not been rigorously investigated. One key question relates to whether lineage-determining factors dictate lineage-specific responses to inductive signals or facilitate these responses in collaboration with other inputs. We utilize the chordate model Ciona robusta to investigate mechanisms generating lineage-specific induction. Previous studies in C. robusta have shown that cardiopharyngeal progenitor cells are specified through the combined activity of FGF-activated Ets1/2.b and an inferred ATTA-binding transcriptional cofactor. Here, we show that the homeobox TF Lhx3/4 serves as the lineage-determining TF that dictates cardiopharyngeal-specific transcription in response to pleiotropic FGF signaling. Targeted knockdown of Lhx3/4 leads to loss of cardiopharyngeal gene expression. Strikingly, ectopic expression of Lhx3/4 in a neuroectodermal lineage subject to FGF-dependent specification leads to ectopic cardiopharyngeal gene expression in this lineage. Furthermore, ectopic Lhx3/4 expression disrupts neural plate morphogenesis, generating aberrant cell behaviors associated with execution of incompatible morphogenetic programs. Based on these findings, we propose that combinatorial regulation by signal-dependent and lineage-determinant factors represents a generalizable, previously uncategorized regulatory subcircuit we term "cofactor-dependent induction." Integration of this subcircuit into theoretical models will facilitate accurate predictions regarding the impact of gene regulatory network rewiring on evolutionary diversification and disease ontogeny.

ANISEED 2019: 4D exploration of genetic data for an extended range of tunicates.

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.

Traumatic brain injury increases plasma astrocyte-derived exosome levels of neurotoxic complement proteins.

Possible involvement of complement (C) systems in the pathogenesis of traumatic brain injury (TBI) was investigated by quantifying Cproteins in plasma astrocyte-derived exosomes (ADEs) of subjects with sports-related TBI (sTBI) and TBI in military veterans (mtTBI) without cognitive impairment. All sTBI subjects (n = 24) had mild injuries, whereas eight of the mtTBI subjects had moderate, and 17 had mild injuries. Plasma levels of ADEs were decreased after acute sTBI and returned to normal within months. Cprotein levels in ADEs were from 12- to 35-fold higher than the corresponding levels in neuron-derived exosomes. CD81 exosome marker-normalized ADE levels of classical pathway C4b, alternative pathway factor D and Bb, lectin pathway mannose-binding lectin (MBL), and shared neurotoxic effectors C3b and C5b-9 terminal C complex were significantly higher and those of C regulatory proteins CR1 and CD59 were lower in the first week of acute sTBI (n = 12) than in controls (n = 12). Most C abnormalities were no longer detected in chronic sTBI at 3-12 months after acute sTBI, except for elevated levels of factor D, Bb, and MBL. In contrast, significant elevations of ADE levels of C4b, factor D, Bb, MBL, C3b and C5b-9 terminal C complex, and depressions of CR1 and CD59 relative to those of controls were observed after 1-4 years in early chronic mtTBI (n = 10) and persisted for decades except for normalization of Bb, MBL, and CD59 in late chronic mtTBI (n = 15). Complement inhibitors may be useful therapeutically in acute TBI and post-concussion syndrome.

Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury.

Neuron-derived exosomes (NDEs) were enriched by anti-L1CAM antibody immunoabsorption from plasmas of subjects ages 18-26 yr within 1 wk after a sports-related mild traumatic brain injury (acute mTBI) ( n = 18), 3 mo or longer after the last of 2-4 mTBIs (chronic mTBI) ( n = 14) and with no recent history of TBI (controls) ( n = 21). Plasma concentrations of NDEs, assessed by counts and levels of extracted exosome marker CD81, were significantly depressed by a mean of 45% in acute mTBI ( P < 0.0001), but not chronic mTBI, compared with controls. Mean CD81-normalized NDE levels of a range of functional brain proteins were significantly abnormal relative to those of controls in acute but not chronic mTBI, including ras-related small GTPase 10, 73% decrease; annexin VII, 8.8-fold increase; ubiquitin C-terminal hydrolase L1, 2.5-fold increase; AII spectrin fragments, 1.9-fold increase; claudin-5, 2.7-fold increase; sodium-potassium-chloride cotransporter-1, 2.8-fold increase; aquaporin 4, 8.9-fold increase (3.6-fold increase in chronic mTBI); and synaptogyrin-3, 3.1-fold increase (1.3-fold increase in chronic mTBI) (all acute mTBI proteins P < 0.0001). In chronic mTBI, there were elevated CD81-normalized NDE levels of usually pathologic ß-amyloid peptide 1-42 (1.6-fold, P < 0.0001), P-T181-tau (2.2-fold, P < 0.0001), P-S396-tau (1.6-fold, P < 0.01), IL-6 (16-fold, P < 0.0001), and prion cellular protein (PRPc) (5.1-fold, P < 0.0001) with lesser or greater (IL-6, PRPc) increases in acute mTBI. Increases in NDE levels of most neurofunctional proteins in acute, but not chronic, mTBI, and elevations of most NDE neuropathological proteins in chronic and acute mTBI delineated phase-specificity. Longitudinal studies of more mTBI subjects may identify biomarkers predictive of and etiologically involved in mTBI-induced neurodegeneration.-Goetzl, E. J., Elahi, F. M., Mustapic, M., Kapogiannis, D., Pryhoda, M., Gilmore, A., Gorgens, K. A., Davidson, B., Granholm, A.-C., Ledreux, A. Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury.

Centre of pressure velocity shows impairments in NCAA Division I athletes six months post-concussion during standing balance.

Sport-related concussion return to play (RTP) decisions are largely based on the resolution of self-reported symptoms and neurocognitive function. Some evaluators also incorporate balance; however, an objective approach to balance that can detect effects beyond the acute condition is warranted. The purpose of this study is to examine linear measures of biomechanical balance up to 6 months post-concussion, and to present preliminary diagnostic thresholds useful for RTP. Each concussed athlete participated in instrumented standing balance tasks at 4 timepoints post-concussion. The measures from concussed athletes were compared to the sport-matched non-concussed athlete group at each timepoint. Centre of pressure (COP) mediolateral (ML) velocity in double-leg stance on a hard surface discriminated well between non-concussed and concussed athletes. COP anterior-posterior (AP) velocity in tandem stance on foam showed sensitivity to concussion. Sixty per cent of athletes at 6 months post-concussion did not recover to within the proposed COP ML velocity threshold in double-leg stance on a hard surface. Seventy-one per cent of athletes at 6 months post-concussion did not recover to within the COP AP velocity threshold in tandem stance on foam. This lack of recovery potentially indicates vestibular and motor control impairments long past the typical period of RTP.

Deep Learning in Gait Parameter Prediction for OA and TKA Patients Wearing IMU Sensors.

Quantitative assessments of patient movement quality in osteoarthritis (OA), specifically spatiotemporal gait parameters (STGPs), can provide in-depth insight into gait patterns, activity types, and changes in mobility after total knee arthroplasty (TKA). A study was conducted to benchmark the ability of multiple deep neural network (DNN) architectures to predict 12 STGPs from inertial measurement unit (IMU) data and to identify an optimal sensor combination, which has yet to be studied for OA and TKA subjects. DNNs were trained using movement data from 29 subjects, walking at slow, normal, and fast paces and evaluated with cross-fold validation over the subjects. Optimal sensor locations were determined by comparing prediction accuracy with 15 IMU configurations (pelvis, thigh, shank, and feet). Percent error across the 12 STGPs ranged from 2.1% (stride time) to 73.7% (toe-out angle) and overall was more accurate in temporal parameters than spatial parameters. The most and least accurate sensor combinations were feet-thighs and singular pelvis, respectively. DNNs showed promising results in predicting STGPs for OA and TKA subjects based on signals from IMU sensors and overcomes the dependency on sensor locations that can hinder the design of patient monitoring systems for clinical application.

Lumbar Intervertebral Kinematics During an Unstable Sitting Task and Its Association With Standing-Induced Low Back Pain.

People developing transient low back pain during standing have altered control of their spine and hips during standing tasks, but the transfer of these responses to other tasks has not been assessed. This study used video fluoroscopy to assess lumbar spine intervertebral kinematics of people who do and do not develop standing-induced low back pain during a seated chair-tilting task. A total of 9 females and 8 males were categorized as pain developers (5 females and 3 males) or nonpain developers (4 females and 5 males) using a 2-hour standing exposure; pain developers reported transient low back pain and nonpain developers did not. Participants were imaged with sagittal plane fluoroscopy at 25 Hz while cyclically tilting their pelvises anteriorly and posteriorly on an unstable chair. Intervertebral angles, relative contributions, and anterior-posterior translations were measured for the L3/L4, L4/L5, and L5/S1 joints and compared between sexes, pain groups, joints, and tilting directions. Female pain developers experienced more extension in their L5/S1 joints in both tilting directions compared with female nonpain developers, a finding not present in males. The specificity in intervertebral kinematics to sex-pain group combinations suggests that these subgroups of pain developers and nonpain developers may implement different control strategies.

Evaluation of Novel EMG Biofeedback for Postural Correction During Computer Use.

Postural correction is an effective rehabilitation technique used to treat chronic neck and shoulder pain, and is aimed toward reducing the load on the surrounding muscles by adopting a neutral posture. The objective of this investigation was to evaluate the effectiveness of real-time high-density surface EMG (HDsEMG) biofeedback for postural correction during typing. Twenty healthy participants performed a typing task with two forms of postural feedback: (1) verbal postural coaching and (2) verbal postural coaching plus HDsEMG biofeedback. The interface used activity from two HDsEMG arrays placed over the trapezius designed to shift trapezius muscle activity inferiorly. The center of gravity across both arrays was used to quantify the spatial distribution of trapezius activity. Planar angles taken from upper extremity reflective markers quantified cervicoscapular posture. During the biofeedback condition, trapezius muscle activity was located 12.74 ± 3.73 mm more inferior, the scapula was 2.58 ± 1.18° more adducted and 0.23 ± 0.24° more depressed in comparison to verbal postural coaching alone. The results demonstrate the short-term effectiveness of a real-time HDsEMG biofeedback intervention to achieve postural correction, and may be more effective at creating an inferior shift in trapezius muscle activity in comparison to verbal postural coaching alone.

Methods of Muscle Activation Onset Timing Recorded During Spinal Manipulation.

OBJECTIVE: The purpose of this study was to determine electromyographic threshold parameters that most reliably characterize the muscular response to spinal manipulation and compare 2 methods that detect muscle activity onset delay: the double-threshold method and cross-correlation method. METHODS: Surface and indwelling electromyography were recorded during lumbar side-lying manipulations in 17 asymptomatic participants. Muscle activity onset delays in relation to the thrusting force were compared across methods and muscles using a generalized linear model. RESULTS: The threshold combinations that resulted in the lowest Detection Failures were the "8 SD-0 milliseconds" threshold (Detection Failures = 8) and the "8 SD-10 milliseconds" threshold (Detection Failures = 9). The average muscle activity onset delay for the double-threshold method across all participants was 149 ± 152 milliseconds for the multifidus and 252 ± 204 milliseconds for the erector spinae. The average onset delay for the cross-correlation method was 26 ± 101 for the multifidus and 67 ± 116 for the erector spinae. There were no statistical interactions, and a main effect of method demonstrated that the delays were higher when using the double-threshold method compared with cross-correlation. CONCLUSIONS: The threshold parameters that best characterized activity onset delays were an 8-SD amplitude and a 10-millisecond duration threshold. The double-threshold method correlated well with visual supervision of muscle activity. The cross-correlation method provides several advantages in signal processing; however, supervision was required for some results, negating this advantage. These results help standardize methods when recording neuromuscular responses of spinal manipulation and improve comparisons within and across investigations.

The Neuromuscular Response to Spinal Manipulation in the Presence of Pain.

OBJECTIVE: The purpose of this study was to evaluate differences in muscle activity in participants with and without low back pain during a side-lying lumbar diversified spinal manipulation. METHODS: Surface and indwelling electromyography at eight muscle locations were recorded during lumbar side-lying manipulations in 20 asymptomatic participants and 20 participants with low back pain. The number of muscle responses and muscle activity onset delays in relation to the manipulation impulse were compared in the 2 pain groups using mixed linear regressions. Effect sizes for all comparisons were calculated using Cohen's d. RESULTS: Muscle responses occurred in 61.6% ± 23.6% of the EMG locations in the asymptomatic group and 52.8% ± 26.3% of the symptomatic group. The difference was not statistically significant but there was a small effect of pain (d = 0.350). Muscle activity onset delays were longer for the symptomatic group at every EMG location except the right side indwelling L5 electrode, and a small effect of pain was present at the left L2, quadratus lumborum and trapezius surface electrodes (d = 0.311, 0.278, and 0.265) respectively. The indwelling electrodes demonstrated greater muscle responses (P ≤ .01) and shorter muscle activity onset delays (P < .01) than the surface electrodes. CONCLUSIONS: The results revealed trends that indicate participants with low back pain have less muscle responses, and when muscle responses are present they occur with longer onset delays following the onset of a manipulation impulse.

Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans.

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

Acquisition of polymorphism in the chordate doliolids.

In polymorphic organisms a single genome is deployed to program numerous, morphologically distinct body plans within a colony. This complex life history trait has evolved independently within a limited subset of animal taxa. Reconstructing the underlying genetic, cellular and developmental changes that drove the emergence of polymorphic colonies represents a promising avenue for exploring diversifying selection and resulting impacts on developmental gene regulatory networks. Doliolids are the only polymorphic chordate, deploying a single genome to program distinct morphs specialized for locomotion, feeding, asexual or sexual reproduction. In this review, we provide a detailed summary of doliolid anatomy, development, taxonomy, ecology, life history and the cellular basis for doliolid polymorphism. In order to frame the potential evolutionary and developmental insights that could be gained by studying doliolids we provide a broader overview of polymorphism. We then discuss how comparative studies of polymorphic cnidarians have begun to illuminate the genetic basis of this unusual and complex life history strategy. We then provide a summary of life history divergence in the chordates, particularly among doliolids and their polymorphic cousins, the salps and pyrosomes.

Cylindrical axis, not epicondyles, approximates perpendicular to knee axes.

BACKGROUND: The transepicondylar axis (TEA) is often used as a surrogate for the flexion-extension axis, ie, the axis around which the tibia moves in space, because of a belief that both axes lie perpendicular to the mechanical axis. However, studies suggest the cylindrical axis (CA), defined as a line equidistant from contact points on the medial and lateral condylar surfaces from 10(o) to 120(o) flexion, more closely approximates the axis around which the tibia moves in space. QUESTIONS/PURPOSES: We examined the TEA and CA angles relative to mechanical axes to determine whether one more consistently and closely approximates the surgical goal of orthogonality to the mechanical axis. METHODS: Three-dimensional (3-D) models were reconstructed from CT scans of five cadaver limbs. Three observers repeated three measurement sets to locate the TEA, CA, and femoral mechanical and tibial mechanical axes. Angles of the TEA and CA relative to the mechanical axes were calculated in two-dimensions (2-D) and as 3-D projections and compared for differences in magnitude and variance. RESULTS: Angles between CA and the mechanical axes were closer to 90° than the TEA in 2-D (92° versus 94° for the femur, 93° versus 94° for the tibia) and 3-D (88° versus 87° for the femur, 88° versus 86° for the tibia). Variance of the TEA was higher than the CA in 2-D. CONCLUSIONS: The CA forms angles more orthogonal to the mechanical axes of the thigh and leg than the TEA. CLINICAL RELEVANCE: Although we found a consistently greater deviation of the TEA from the mechanical axis than the CA with small differences, future studies will need to determine whether these differences are biomechanically or clinically important.

Treatment and Response Factors in Muscle Activation during Spinal Manipulation.

The forces applied during a spinal manipulation produce a neuromuscular response in the paraspinal muscles. A systematic evaluation of the factors involved in producing this muscle activity provides a clinical insight. The purpose of this study is to quantify the effect of treatment factors (manipulation sequence and manipulation site) and response factors (muscle layer, muscle location, and muscle side) on the neuromuscular response to spinal manipulation. The surface and indwelling electromyographies of 8 muscle sites were recorded during lumbar side-lying manipulations in 20 asymptomatic participants. The effects of the factors on the number of muscle responses and the muscle activity onset delays were compared using mixed-model linear regressions, effect sizes, and equivalence testing. The treatment factors did not reveal statistical differences between the manipulation sequences (first or second) or manipulation sites (L3 or SI) in the number of muscle responses (p = 0.11, p = 0.28, respectively), or in muscle activity onset delays (p = 0.35 p = 0.35, respectively). There were significantly shorter muscle activity onset delays in the multifidi compared to the superficial muscles (p = 0.02). A small effect size of side (d = 0.44) was observed with significantly greater number of responses (p = 0.02) and shorter muscle activity onset delays (p < 0.001) in the muscles on the left side compared to the right. The location, layer, and side of the neuromuscular responses revealed trends of decreasing muscle response rates and increasing muscle activity onset delays as the distance from the manipulation site increased. These results build on the body of work suggesting that the specificity of manipulation site may not play a role in the neuromuscular response to spinal manipulation-at least within the lumbar spine. In addition, these results demonstrate that multiple manipulations performed in similar areas (L3 and S1) do not change the response significantly, as well as contribute to the clinical understanding that the muscle response rate is higher and with a shorter delay, the closer it is to the manipulation.

Optimized prediction of contact force application during side-lying lumbar manipulation.

OBJECTIVES: The purposes of this study included the following: (1) to predict L3 contact force during side-lying lumbar manipulation by combining direct and indirect measurements into a single mathematical framework and (2) to assess the accuracy and confidence of predicting L3 contact force using common least squares (CLS) and weighted least squares (WLS) methods. METHODS: Five participants with no history of lumbar pain underwent 10 high-velocity, low-amplitude lumbar spinal manipulations at L3 in a side-lying position. Data from 5 low-force criterion standard trials where the L3 contact force was directly measured were used to generate participant-specific force prediction algorithms. These algorithms were used to predict L3 contact force in 5 experimental trials performed at therapeutic levels. The accuracy and effectiveness of CLS and WLS methods were compared. RESULTS: Differences between the CLS-predicted forces and the criterion standard-measured forces were 621.0 ± 193.5 N. Differences between the WLS-predicted forces and the criterion standard-measured forces were -3.6 ± 9.1 N. The 95% limits of agreement ranged from 234.0 to 1008.0 N for the CLS and -21.9 to 14.7 N for the WLS. During both the criterion standard and experimental trials, the CLS overestimated contact forces with larger variance than the WLS. CONCLUSION: This novel method to predict spinal contact force combines direct and indirect measurements into a single framework and preserves clinically relevant practitioner-participant contacts. As advanced instrumentation becomes available, this framework will enable advancements in training and high-quality research on mechanisms of spinal manipulative therapy.

Pro-inflammatory cytokines expression increases following low- and high-magnitude cyclic loading of lumbar ligaments.

Repetitive or overuse disorders of the lumbar spine affect the lives of workers and athletes. We hypothesize that repetitive anterior lumbar flexion-extension under low or high load will result in significantly elevated pro-inflammatory cytokines expression several hours post-activity. High loads will exhibit significantly higher expression than low loads. Lumbar spine of in vivo feline was subjected to cyclic loading at 0.25 Hz for six 10-min periods with 10 min of rest in between. One group was subjected to a low peak load of 20 N, whereas the second group to a high peak load of 60 N. Following a 7-h post-loading rest, the supraspinous ligaments of L-3/4, L-4/5 and L-5/6 and the unstimulated T-10/11 were excised for mRNA analysis and IL-1beta, IL-6, IL-8, TNFalpha and TGFbeta1 pro-inflammatory cytokines expression. Creep (laxity) developed in the lumbar spine during the loading and the subsequent 7 h of rest was calculated. A two-way mixed model ANOVA was used to assess difference in each cytokines expression between the two groups and control. Tukey HSD post hoc analysis delineated specific significant effects. Significance was set at 0.05. Low and high-load groups exhibited development of creep throughout the cyclic loading period and gradual recovery throughout the 7-h rest period. Residual creep of 24.8 and 30.2% were present in the low and high-load groups, respectively, 7-h post-loading. Significant increases in expression of all cytokines measured relative to control were obtained for supraspinous ligaments from both low and high-load magnitudes. IL-6, IL-8 and TGFbeta1 expression in the high-load group were significantly higher relative to the low-load group. Significant increases in cytokines expression indicating tissue inflammation are observed several hours post-repetitive lumbar flexion-extension regardless of the load magnitude applied. Repetitive occupational and athletic activity, regardless of the load applied, may be associated with the potential of developing acute inflammatory conditions that may convert to chronic inflammation if the viscoelastic tissues are further exposed to repetitive activity over long periods. Appropriate rest periods are a relevant preventive measure.

Inferring Tunicate Relationships and the Evolution of the Tunicate Hox Cluster with the Genome of Corella inflata.

Tunicates, the closest living relatives of vertebrates, have served as a foundational model of early embryonic development for decades. Comparative studies of tunicate phylogeny and genome evolution provide a critical framework for analyzing chordate diversification and the emergence of vertebrates. Toward this goal, we sequenced the genome of Corella inflata (Ascidiacea, Phlebobranchia), so named for the capacity to brood self-fertilized embryos in a modified, "inflated" atrial chamber. Combining the new genome sequence for Co. inflata with publicly available tunicate data, we estimated a tunicate species phylogeny, reconstructed the ancestral Hox gene cluster at important nodes in the tunicate tree, and compared patterns of gene loss between Co. inflata and Ciona robusta, the prevailing tunicate model species. Our maximum-likelihood and Bayesian trees estimated from a concatenated 210-gene matrix were largely concordant and showed that Aplousobranchia was nested within a paraphyletic Phlebobranchia. We demonstrated that this relationship is not an artifact due to compositional heterogeneity, as had been suggested by previous studies. In addition, within Thaliacea, we recovered Doliolida as sister to the clade containing Salpida and Pyrosomatida. The Co. inflata genome provides increased resolution of the ancestral Hox clusters of key tunicate nodes, therefore expanding our understanding of the evolution of this cluster and its potential impact on tunicate morphological diversity. Our analyses of other gene families revealed that several cardiovascular associated genes (e.g., BMP10, SCL2A12, and PDE2a) absent from Ci. robusta, are present in Co. inflata. Taken together, our results help clarify tunicate relationships and the genomic content of key ancestral nodes within this phylogeny, providing critical insights into tunicate evolution.

A comparison of trunk control in people with no history, standing-induced, and recurrent low back pain during trunk extension.

Objectives: This study compares people with recurrent low back pain (rLBP) and people with pre-clinical low back pain (standing-induced low back pain developers; PDs) to each other and back-healthy controls (non-pain developers; NPDs). Movement variability and muscular co-activity related to coordination are important for both rLBP and PDs, and these two groups also have altered static spine extension.Methods: Eleven participants with recurrent low back pain, and twenty-one asymptomatic participants, categorized as PDs (11) and NPDs (10) through an established standing protocol, volunteered for this study. Three phases of standing extension motion (lean, hold, and return to neutral) were analyzed. Root mean square angular jerk was calculated from trunk and pelvis kinematics, co-activation of the trunk and hip musculature were assessed in four-muscle sets.Results: Root-mean-square jerk was greater when returning to neutral than when leaning back during standing extension in all three groups. People with rLBP had reduced co-activity in their trunk extensors, people classified as PD had more co-activity in their hip extensors compared with the other groups, and anterior trunk co-activity was phase-dependent, and similar between groups.Discussion: Movement control alterations with low back pain may start as an over-protective co-activation strategy in those with standing-induced LBP and progress to an under-protective strategy in those with recurrent low back pain. Level of Evidence: 3.

Does manual therapy affect functional and biomechanical outcomes of a sit-to-stand task in a population with low back pain? A preliminary analysis.

Introduction: Manual therapy (MT) hypothetically affects discrepant neuromuscular control and movement observed in populations with low back pain (LBP). Previous studies have demonstrated the limited influence of MT on movement, predominately during range of motion (ROM) testing. It remains unclear if MT affects neuromuscular control in mobility-based activities of daily living (ADLs). The sit-to-stand (STS) task represents a commonly-performed ADL that is used in a variety of clinical settings to assess functional and biomechanical performance. Objective: To determine whether MT affects functional performance and biomechanical performance during a STS task in a population with LBP. Methods: Kinematic data were recorded from the pelvis and thorax of participants with LBP, using an optoelectronic motion capture system as they performed a STS task before and after MT from November 2011 to August 2014. MT for each participant consisted of two high-velocity low-amplitude spinal manipulations, as well as two grade IV mobilizations of the lumbar spine and pelvis targeted toward the third lumbar vertebra and sacroiliac joint in a side-lying position; the order of these treatments was randomized. Pelvis and thorax kinematic data were used to derive the time-varying lumbar angle in the sagittal plane for each STS trial. The difference between the maximum and minimum lumbar angles during the STS trial determined the sagittal ROM that was used as the biomechanical outcome. Time to complete each STS trial was used as a functional measure of performance. Pre-MT and post-MT values for the lumbar sagittal ROM and time to completion were statistically analysed using paired samples t-tests. Results: Data were obtained from 40 participants with 35 useful datasets (NRS = 3.3 ± 1.2; 32.4 ± 9.8 years; 16 females, 19 males). After MT, lumbar sagittal ROM increased by 2.7 ± 5.5 degrees (p = 0.007). Time to complete the STS test decreased by 0.4 ± 0.4 s (p < 0.001). Discussion: These findings provide preliminary evidence that MT might influence the biomechanical and functional performance of an STS task in populations with LBP. The MT intervention in this study involved a combination of spinal manipulations and mobilizations. Future work will expand upon these data as a basis for targeted investigations on the effects of either spinal manipulation and mobilization on neuromuscular control and movement in populations with LBP.

A Cohort Study of the Temporal Stability of ImPACT Scores Among NCAA Division I Collegiate Athletes: Clinical Implications of Test-Retest Reliability for Enhancing Student Athlete Safety.

OBJECTIVE: In this study we examined the temporal stability of the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) within NCAA Division I athletes across various timepoints using an exhaustive series of statistical models. METHODS: Within a cohort design, 48 athletes completed repeated baseline ImPACT assessments at various timepoints. Intraclass correlation coefficients (ICC) were calculated using a two-way mixed effects model with absolute agreement. RESULTS: Four ImPACT composite scores (Verbal Memory, Visual Memory, Visual Motor Speed, and Reaction Time) demonstrated moderate reliability (ICC = 0.51-0.66) across the span of a typical Division I athlete's career, which is below previous reliability recommendations (0.90) for measures used in individual decision-making. No evidence of fixed bias was detected within Verbal Memory, Visual Motor Speed, or Reaction Time composite scores, and minimal detectable change values exceeded the limits of agreement. CONCLUSIONS: The demonstrated temporal stability of the ImPACT falls below the published recommendations, and as such, fails to provide robust support for the NCAA's recommendation to obtain a single preparticipation cognitive baseline for use in sports-related concussion management throughout an athlete's career. Clinical interpretation guidelines are provided for clinicians who utilize baseline ImPACT scores for later performance comparisons.