A nomenclature for echinoderm genes.

Echinoderm embryos and larvae are prominent experimental model systems for studying developmental mechanisms. High-quality, assembled, annotated genome sequences are now available for several echinoderm species, including representatives from most classes. The increased availability of these data necessitates the development of a nomenclature that assigns universally interpretable gene symbols to echinoderm genes to facilitate cross-species comparisons of gene functions, both within echinoderms and across other phyla. This paper describes the implementation of an improved set of echinoderm gene nomenclature guidelines that both communicates meaningful orthology information in protein-coding gene symbols and names and establishes continuity with nomenclatures developed for major vertebrate model organisms, including humans. Differences between the echinoderm gene nomenclature guidelines and vertebrate guidelines are examined and explained. This nomenclature incorporates novel solutions to allow for several types of orthologous relationships, including the single echinoderm genes with multiple vertebrate co-orthologs that result from whole-genome-duplication events. The current version of the Echinoderm Gene Nomenclature Guidelines can be found at https://www.echinobase.org/gene/static/geneNomenclature.jsp Database URL https://www.echinobase.org/

Systematic comparison of sea urchin and sea star developmental gene regulatory networks explains how novelty is incorporated in early development.

The extensive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN for endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages. Comparison of the GRNs identifies how novelty is incorporated in early development. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions

Novel Space Alters Theta and Gamma Synchrony Across the Longitudinal Axis of the Hippocampus.

Hippocampal theta (6–10 Hz) and gamma (25–50 Hz and 65–100 Hz) local field potentials (LFPs) reflect the dynamic synchronization evoked by inputs impinging upon hippocampal neurons. Novel experience is known to engage hippocampal physiology and promote successful encoding. Does novelty synchronize or desynchronize theta and/or gamma frequency inputs across the septotemporal (long) axis of the hippocampus (HPC)? The present study tested the hypothesis that a novel spatial environment would alter theta power and coherence across the long axis. We compared theta and gamma LFP signals at individual (power) and millimeter distant electrode pairs (coherence) within the dentate gyrus (DG) and CA1 region while rats navigated a runway (1) in a familiar environment, (2) with a modified path in the same environment and (3) in a novel space. Locomotion in novel space was related to increases in theta and gamma power at most CA1 and DG sites. The increase in theta and gamma power was concurrent with an increase in theta and gamma coherence across the long axis of CA1; however, there was a significant decrease in theta coherence across the long axis of the DG. These findings illustrate significant shifts in the synchrony of entorhinal, CA3 and/or neuromodulatory afferents conveying novel spatial information to the dendritic fields of CA1 and DG targets across the long axis of the HPC. This shift suggests that the entire theta/gamma-related input to the CA1 network, and likely output, receives and conveys a more coherent message in response to novel sensory experience. Such may contribute to the successful encoding of novel sensory experience

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study. Their primary role was to provide remotely delivered weight-loss services (via the Healthy Weight for Life program) to eligible participants in the intervention group. These services were partly provided as in-kind and partly funded through the study. We have received ethical approval from the University of Sydney to replace the Healthy Weight for Life program with the Commonwealth Scientific and Industrial Research Organisation's (CSIRO) Total Wellbeing Diet. The amended weight loss advice and support paragraph of the manuscript is outlined below. All changes to the protocol were made and approved before starting the trial and were prospectively changed on our trial registration (ACT RN12617001595303). Amended weight loss advice and support paragraph: If the patient has a BMI =27 kg/m2, the patient will be offered the option of participating in the remotelydelivered weight loss program. The Australian Commonwealth Scientific and Industrial Research Organisation's (CSIRO) "Total Wellbeing Diet" is based on an evidence-based weight management strategy that utilises a structured, nutritionally balanced eating plan designed to be incorporated into a balanced lifestyle program [2, 3]. The program is a 12- week, low glycaemic index, high protein, healthy eating program with online support and tracking tools, meal plans and educational resources on a healthy diet. It is delivered by SP Health (http://www.sphealth.com/) on behalf of the CSIRO. After completion of the 12-week program, patients may elect to continue the basic program for an additional 12-weeks. Patients who elect to undertake the online weight-loss program will continue to be supported by the PARTNER Care Support Team throughout their time on the weight-loss program. This program will be undertaken in conjunction with the PARTNER exercise program and educational resources on healthy lifestyle change.

Foot posture in people with medial compartment knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Foot posture has long been considered to contribute to the development of lower limb musculoskeletal conditions as it may alter the mechanical alignment and dynamic function of the lower limb. This study compared foot posture in people with and without medial compartment knee osteoarthritis (OA) using a range of clinical foot measures. The reliability of the foot measures was also assessed.</p> <p>Methods</p> <p>The foot posture of 32 patients with clinically and radiographically-confirmed OA predominantly in the medial compartment of the knee and 28 asymptomatic age-matched healthy controls was investigated using the foot posture index (FPI), vertical navicular height and drop, and the arch index. Independent t tests and effect size (Cohen's d) were used to investigate the differences between the groups in the foot posture measurements.</p> <p>Results</p> <p>Significant differences were found between the control and the knee OA groups in relation to the FPI (1.35 ± 1.43 vs. 2.46 ± 2.18, p = 0.02; <it>d </it>= 0.61, medium effect size), navicular drop (0.02 ± 0.01 vs. 0.03 ± 0.01, p = 0.01; <it>d </it>= 1.02, large effect size) and the arch index (0.22 ± 0.04 vs. 0.26 ± 0.04, p = 0.04; <it>d </it>= 1.02, large effect size). No significant difference was found for vertical navicular height (0.24 ± 0.03 vs. 0.23 ± 0.03, p = 0.54; <it>d </it>= 0.04, negligible effect size).</p> <p>Conclusion</p> <p>People with medial compartment knee OA exhibit a more pronated foot type compared to controls. It is therefore recommended that the assessment of patients with knee OA in clinical practice should include simple foot measures, and that the potential influence of foot structure and function on the efficacy of foot orthoses in the management of medial compartment knee OA be further investigated.</p

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study. Their primary role was to provide remotely delivered weight-loss services (via the Healthy Weight for Life program) to eligible participants in the intervention group. These services were partly provided as in-kind and partly funded through the study. We have received ethical approval from the University of Sydney to replace the Healthy Weight for Life program with the Commonwealth Scientific and Industrial Research Organisation's (CSIRO) Total Wellbeing Diet. The amended weight loss advice and support paragraph of the manuscript is outlined below. All changes to the protocol were made and approved before starting the trial and were prospectively changed on our trial registration (ACT RN12617001595303). Amended weight loss advice and support paragraph: If the patient has a BMI =27 kg/m2, the patient will be offered the option of participating in the remotelydelivered weight loss program. The Australian Commonwealth Scientific and Industrial Research Organisation's (CSIRO) "Total Wellbeing Diet" is based on an evidence-based weight management strategy that utilises a structured, nutritionally balanced eating plan designed to be incorporated into a balanced lifestyle program [2, 3]. The program is a 12- week, low glycaemic index, high protein, healthy eating program with online support and tracking tools, meal plans and educational resources on a healthy diet. It is delivered by SP Health (http://www.sphealth.com/) on behalf of the CSIRO. After completion of the 12-week program, patients may elect to continue the basic program for an additional 12-weeks. Patients who elect to undertake the online weight-loss program will continue to be supported by the PARTNER Care Support Team throughout their time on the weight-loss program. This program will be undertaken in conjunction with the PARTNER exercise program and educational resources on healthy lifestyle change.

The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS

We have previously shown that myelin abnormalities characterize the normal aging process of the brain and that an age-associated reduction in Klotho is conserved across species. Predominantly generated in brain and kidney, Klotho overexpression extends life span, whereas loss of Klotho accelerates the development of aging-like phenotypes. Although the function of Klotho in brain is unknown, loss of Klotho expression leads to cognitive deficits. We found significant effects of Klotho on oligodendrocyte functions, including induced maturation of rat primary oligodendrocytic progenitor cells (OPCs) in vitro and myelination. Phosphoprotein analysis indicated that Klotho\u27s downstream effects involve Akt and ERK signal pathways. Klotho increased OPC maturation, and inhibition of Akt or ERK function blocked this effect on OPCs. In vivo studies of Klotho knock-out mice and control littermates revealed that knock-out mice have a significant reduction in major myelin protein and gene expression. By immunohistochemistry, the number of total and mature oligodendrocytes was significantly lower in Klotho knock-out mice. Strikingly, at the ultrastructural level, Klotho knock-out mice exhibited significantly impaired myelination of the optic nerve and corpus callosum. These mice also displayed severe abnormalities at the nodes of Ranvier. To decipher the mechanisms by which Klotho affects oligodendrocytes, we used luciferase pathway reporters to identify the transcription factors involved. Together, these studies provide novel evidence for Klotho as a key player in myelin biology, which may thus be a useful therapeutic target in efforts to protect brain myelin against age-dependent changes and promote repair in multiple sclerosis

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Exercise, education, manual-therapy and taping compared to education for patellofemoral osteoarthritis: a blinded, randomised clinical trial

Objective: Patellofemoral joint osteoarthritis (PFJ OA) contributes considerably to knee OA symptoms. This study aimed to determine the efficacy of a PFJ-targeted exercise, education manual-therapy and taping program compared to OA education alone, in participants with PFJ OA. Methods: A randomised, participant-blinded and assessor-blinded clinical trial was conducted in primary-care physiotherapy. 92 people aged ≥40 years with symptomatic and radiographic PFJ OA participated. Physiotherapists delivered the PFJ-targeted exercise, education, manual-therapy and taping program, or the OA-education (control condition) in eight sessions over 12 weeks.Primary outcomes at 3-month (primary) and 9-month follow-up: (1) patient-perceived global rating of change (2) pain visual analogue scale (VAS) (100 mm); and (3) activities of daily living (ADL) subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS). Results: 81 people (88%) completed the 3-month follow-up and data analysed on an intention-to-treat basis. Between-group baseline similarity for participant characteristics was observed. The exercise, education, manual-therapy and taping program resulted in more people reporting much improvement (20/44) than the OA-education group (5/48) (number needed to treat 3 (95% confidence interval (CI) 2 to 5)) and greater pain reduction (mean difference: -15.2 mm, 95% CI -27.0 to -3.4). No significant effects on ADL were observed (5.8; 95% CI -0.6 to 12.1). At 9 months there were no significant effects for self-report of improvement, pain (-10.5 mm, 95% CI -22.7 to 1.8) or ADL (3.0, 95% CI -3.7 to 9.7). Conclusion: Exercise, education, manual-therapy and taping can be recommended to improve short-term patient rating of change and pain severity. However over 9-months, both options were equivalent. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000288325): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82878

A ventral rotational skin flap to improve cosmesis and avoid chordee recurrence in epispadias repair.

OBJECTIVE: To describe a technical modification that facilitates dorsal skin closure, improves cosmesis and eliminates chordee recurrence secondary to contracture of the dorsal penile skin in the repair of epispadias. PATIENTS AND METHODS: Eleven patients with penopubic epispadias (mean age 1.8 years) had the epispadias repaired using a modified ventral penile skin flap. Four patients had isolated epispadias and seven had had a previous primary closure of bladder exstrophy. Nine patients underwent the Cantwell-Ransley technique, leaving the meatus in a glanular position. Two patients were repaired using the penile disassembly technique of Mitchell and Bägli, because they had a short urethral plate. A ventral island skin flap was fashioned, starting at the base of the penis. Dissection was carried ventrally into the scrotum to allow for adequate dorsal flap transposition. The flap was rotated laterally to shift the suture line from the midline and to cover the dorsal aspect of the penis with untouched penile shaft skin. Redundant ventral foreskin was discarded. RESULTS: All patients had an uneventful course after surgery. Dorsal penile skin was viable in every case and no patient developed recurrence of chordee or a urethrocutaneous fistula. The cosmetic result was excellent in all patients. CONCLUSIONS: Dorsal skin closure using lateral rotation of ventral penile skin flap improves cosmesis after epispadias repair and eliminates the recurrence of chordee secondary to midline dorsal scarring