Kinematic characteristics of barefoot sprinting in habitually shod children

Background. Anecdotally, a wide variety of benefits of barefoot running have been advocated by numerous individuals. The influence of the alterations in the properties of the shoe on the running movement has been demonstrated in adults at submaximal jogging speeds. However, the biomechanical differences between shod and barefoot running in children at sprinting speeds and the potential developmental implications of these differences are still less examined. The purpose was to determine the potential differences in habitually shod children's sprint kinematics between shod and barefoot conditions. Methods. Ninety-four children (51 boys and 43 girls; 6-12 years-old; height, 135.0 ± 0.12 m; body mass, 29.0 ± 6.9 kg) performed 30 m maximal sprints from standing position for each of two conditions (shod and barefoot). To analyze sprint kinematics within sagittal plane sprint kinematics, a high-speed camera (300 fps) was set perpendicular to the runway. In addition, sagittal foot landing and take-offimages were recorded for multiple angles by using five high-speed cameras (300 fps). Spatiotemporal variables, the kinematics of the right leg (support leg) and the left leg (recovery leg), and foot strike patterns: rear-foot strike (RFS), mid-foot strike (MFS), and forefoot strike (FFS) were investigated. The paired t -test was used to test difference between shod and barefoot condition. Results. Barefoot sprinting in habitually shod children was mainly characterized by significantly lower sprint speed, higher step frequency, shorter step length and stance time. In shod running, 82% of children showed RFS, whereas it decreased to 29% in barefoot condition. The touch down state and the subsequent joint movements of both support and recovery legs during stance phase were significantly altered when running in condition with barefoot. Discussion. The acute effects of barefoot sprinting was demonstrated by significantly slower sprinting speeds that appear to reflect changes in a variety of spatiotemporal parameters as well as lower limb kinematics. It is currently unknown whether such differences would be observed in children who typically run in bare feet and what developmental benefits and risks may emerge from increasing the proportion of barefoot running and sprinting in children. Future research should therefore investigate potential benefits that barefoot sprinting may have on the development of key physical fitness such as nerve conduction velocity, muscular speed, power, and sprinting technique and on ways to minimize the risk of any acute or chronic injuries associated with this activity. © 2018 Mizushima et al

α- and β-Tubulin Lattice of the Axonemal Microtubule Doublet and Binding Proteins Revealed by Single Particle Cryo-Electron Microscopy and Tomography

SummaryMicrotubule doublet (MTD) is the main skeleton of cilia/flagella. Many proteins, such as dyneins and radial spokes, bind to MTD, and generate or regulate force. While the structure of the reconstituted microtubule has been solved at atomic resolution, nature of the axonemal MTD is still unclear. There are a few hypotheses of the lattice arrangement of its α- and β-tubulins, but it has not been described how dyneins and radial spokes bind to MTD. In this study, we analyzed the three-dimensional structure of Tetrahymena MTD at ∼19 Å resolution by single particle cryo-electron microscopy. To identify α- and β-tubulins, we combined image analysis of MTD with specific kinesin decoration. This work reveals that α- and β-tubulins form a B-lattice arrangement in the entire MTD with a seam at the outer junction. We revealed the unique way in which inner arm dyneins, radial spokes, and proteins inside MTD bind and bridge protofilaments

The distinct distribution of two Dictyostelium Talins

Although the distinct distribution of certain molecules along the anterior or posterior edge is essential for directed cell migration, the mechanisms to maintain asymmetric protein localization have not yet been fully elucidated. Here, we studied a mechanism for the distinct localizations of two Dictyostelium talin homologues, talin A and talin B, both of which play important roles in cell migration and adhesion. Using GFP fusion, we found that talin B, as well as its C-terminal actin-binding region, which consists of an I/LWEQ domain and a villin headpiece domain, was restricted to the leading edge of migrating cells. This is in sharp contrast to talin A and its C-terminal actin-binding domain, which co-localized with myosin II along the cell posterior cortex, as reported previously. Intriguingly, even in myosin II-null cells, talin A and its actin-binding domain displayed a specific distribution, co-localizing with stretched actin filaments. In contrast, talin B was excluded from regions rich in stretched actin filaments, although a certain amount of its actin-binding region alone was present in those areas. When cells were sucked by a micro-pipette, talin B was not detected in the retracting aspirated lobe where acto-myosin, talin A, and the actin-binding regions of talin A and talin B accumulated. Based on these results, we suggest that talin A predominantly interacts with actin filaments stretched by myosin II through its C-terminal actin-binding region, while the actin-binding region of talin B does not make such distinctions. Furthermore, talin B appears to have an additional, unidentified mechanism that excludes it from the region rich in stretched actin filaments. We propose that these actin-binding properties play important roles in the anterior and posterior enrichment of talin B and talin A, respectively, during directed cell migration

Conformational diversity of dynactin

Dynactin is a principal regulator of the minus-end directed microtubule motor dynein. The sidearm of dynactin is essential for binding to microtubules and regulation of dynein activity. Although our understanding of the structure of the dynactin backbone (Arp1 rod) has greatly improved recently, structural details of the sidearm subcomplex remain elusive. Here, we report the flexible nature and diverse conformations of dynactin sidearm observed by electron microscopy. Using nanogold labeling and deletion mutant analysis, we determined the domain organization of the largest subunit p150 and discovered that its coiled-coil (CC1), dynein-binding domain, adopted either a folded or an extended form. Furthermore, the entire sidearm exhibited several characteristic forms, and the equilibrium among them depended on salt concentrations. These conformational diversities of the dynactin complex provide clues to understanding how it binds to microtubules and regulates dynein

Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line

Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it

Kinematic characteristics of barefoot sprinting in habitually shod children

BackgroundAnecdotally, a wide variety of benefits of barefoot running have been advocated by numerous individuals. The influence of the alterations in the properties of the shoe on the running movement has been demonstrated in adults at submaximal jogging speeds. However, the biomechanical differences between shod and barefoot running in children at sprinting speeds and the potential developmental implications of these differences are still less examined. The purpose was to determine the potential differences in habitually shod children’s sprint kinematics between shod and barefoot conditions.MethodsNinety-four children (51 boys and 43 girls; 6–12 years-old; height, 135.0 ± 0.12 m; body mass, 29.0 ± 6.9 kg) performed 30 m maximal sprints from standing position for each of two conditions (shod and barefoot). To analyze sprint kinematics within sagittal plane sprint kinematics, a high-speed camera (300 fps) was set perpendicular to the runway. In addition, sagittal foot landing and take-off images were recorded for multiple angles by using five high-speed cameras (300 fps). Spatio-temporal variables, the kinematics of the right leg (support leg) and the left leg (recovery leg), and foot strike patterns: rear-foot strike (RFS), mid-foot strike (MFS), and fore-foot strike (FFS) were investigated. The paired t-test was used to test difference between shod and barefoot condition.ResultsBarefoot sprinting in habitually shod children was mainly characterized by significantly lower sprint speed, higher step frequency, shorter step length and stance time. In shod running, 82% of children showed RFS, whereas it decreased to 29% in barefoot condition. The touch down state and the subsequent joint movements of both support and recovery legs during stance phase were significantly altered when running in condition with barefoot.DiscussionThe acute effects of barefoot sprinting was demonstrated by significantly slower sprinting speeds that appear to reflect changes in a variety of spatiotemporal parameters as well as lower limb kinematics. It is currently unknown whether such differences would be observed in children who typically run in bare feet and what developmental benefits and risks may emerge from increasing the proportion of barefoot running and sprinting in children. Future research should therefore investigate potential benefits that barefoot sprinting may have on the development of key physical fitness such as nerve conduction velocity, muscular speed, power, and sprinting technique and on ways to minimize the risk of any acute or chronic injuries associated with this activity

The Surgical Benefits of Repeat Hepatectomy for Colorectal Liver Metastasis

The most common site of distant metastasis from colorectal cancer is the liver, and hepatectomy presents the best curative treatment for recurrence of colorectal liver metastasis （CRLM）. This study aimed to identify factors of prognostic value for repeat hepatectomy for CRLM and to determine whether a third such procedure could similarly produce favourable outcomes for CRLM. We analyzed data for 161 patients in our department with colorectal metastasis. Of these, 22 patients underwent repeat hepatectomy for recurrent metastasis, with 16 undergoing a second hepatectomy and 6 a third hepatectomy. We analyzed patient characteristics, tumor status, operation-related variables, and short- and long-term outcomes. Univariate analysis for repeat hepatectomy identified the following five prognostic risk factors: T factor （＞SE） of the primary cancer, number of tumors involved in the initial hepatectomy （＞5）, interval from first to second hepatectomy （＜1year）, number of tumors involved in second hepatectomy （＞3）, and post-operation time （＞30days）. By multivariate analysis, T factor （＞SE） of the primary cancer, number of tumors in the initial hepatectomy （＞5）, and number of tumors in the second hepatectomy （＞3） were independently associated with a worse survival after surgery for CRLM. Although surgical outcomes of the third hepatectomy were not compared with those of the first and second hepatectomy, there were no obvious differences, nor did the 1-, 3-, and 5-year survival rates differ significantly among the three groups. Repeat hepatectomy for CRLM could improve long-term survival. In addition, patients undergoing a third hepatectomy showed a similar survival benefit to those having one or two resections

Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine

新規光駆動型イオンチャネルの構造解明と高性能分子ツールの創出 --神経科学に光を当てる--. 京都大学プレスリリース. 2022-02-03.ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology

Japanese cross-cultural validation study of the Pain Stage of Change Questionnaire.

Introduction:Although evidence supports efficacy of treatments that enhance self-management of chronic pain, the efficacy of these treatments has been hypothesized to be influenced by patient readiness for self-management. The Pain Stage of Change Questionnaire (PSOCQ) is a reliable and valid measure of patient readiness to self-manage pain. However, there is not yet a Japanese version of the PSOCQ (PSOCQ-J), which limits our ability to evaluate the role of readiness for pain self-management in function and treatment response in Japanese patients with chronic pain.Objective:Here, we sought to develop the PSOCQ-J and evaluate its psychometric properties.Methods:We recruited 201 patients with chronic pain. The study participants were asked to complete the PSOCQ-J and other measures assessing pain severity, pain interference, catastrophizing, self-efficacy, and pain coping strategies.Results:The results supported a 4-factor structure of the PSOCQ-J. We also found good to excellent internal consistencies and good test-retest reliabilities for the 4 scales. The Precontemplation scale had weak to moderate positive correlations with measures of pain-related dysfunction and maladaptive coping. The Action and Maintenance scales had weak to moderate positive correlations with measures of self-efficacy and adaptive coping. The Contemplation scale had weak positive correlations with measures of pain interference and both adaptive and maladaptive coping.Conclusions:The PSOCQ-J demonstrated adequate psychometric properties in a sample of Japanese patients with chronic pain. This measure can be used to evaluate the role that readiness to self-manage pain may play in adjustment to chronic pain in Japanese pain populations