Differences in lower extremity kinematics during single-leg lateral drop landing of healthy individuals, injured but asymptomatic patients, and patients with chronic ankle instability- a cross-sectional observational study.

The lower-extremity kinematics associated with forward jump landing after an ankle injury is known to differ for patients with Chronic Ankle Instability (CAI), copers (injured but asymptomatic patients), and healthy individuals. However, the differences in the lower extremity kinematics of these groups associated with a Single-leg Lateral Drop Landing (SLDL) are unknown. The purpose of this study is to characterize the lower limb and foot kinematics during SLDL in CAI patients and to compare these characteristics with those of the copers and healthy individuals. This was a cross-sectional observational study. Nineteen participants, each, were selected from the CAI, Coper, and control groups. The lower-extremity kinematics during SLDL was measured using three-dimensional motion analysis over an interval progressing from 200 ms before landing to 200 ms after landing. Either one-way ANOVA or the Kruskal-Wallis test was used to compare the attributes of the respective groups, with each parameter measured every 10 ms. The maximum values and excursions of the parameters were established over time intervals progressing from 200 ms before landing to 200 ms after landing. Significant observations were subjected to post hoc analysis. Compared to the Coper group, the CAI group exhibited significantly smaller hip adduction angles at 160 ms, ankle dorsiflexion angles in the 110-150 ms interval, and maximum ankle dorsiflexion angles after landing. Compared to the control group, the CAI group exhibited significantly smaller excursions of MH inversion/eversion after landing. Our findings confirm the necessity of focusing on the kinematics of hip adduction/abduction and plantar/dorsiflexion during SLDL in evaluating patients with ankle injuries.

Transcranial direct current stimulation improves motor function in rats with 6-hydroxydopamine-induced Parkinsonism.

Transcranial direct current stimulation (tDCS) is increasingly being used for Parkinson's disease (PD); however, the evaluation of its clinical impact remains complex owing to the heterogeneity of patients and treatments. Therefore, we used a unilateral 6-hydroxydopamine-induced PD rat model to investigate whether anodal tDCS of the primary motor cortex (M1) alleviates PD motor deficits. Before tDCS treatment, unilateral PD rats preferentially used the forelimb ipsilateral to the lesion in the exploratory cylinder test and showed reduced locomotor activity in the open field test. In addition, PD-related clumsy forelimb movements during treadmill walking were detected using deep learning-based video analysis (DeepLabCut). When the 5-day tDCS treatment began, the forelimb-use asymmetry was ameliorated gradually, and locomotor activity increased to pre-lesion levels. tDCS treatment also normalized unnatural forelimb movement during walking and restored a balanced gait. However, these therapeutic effects were rapidly lost or gradually disappeared when the tDCS treatment was terminated. Histological analysis at the end of the experiment revealed that the animals had moderately advanced PD, with 40-50% of dopamine neurons and fibers preserved on the injured side compared with those on the intact side. Although it remains a challenge to elucidate the neural mechanisms of the transient improvement in motor function induced by tDCS, the results of this study provide evidence that tDCS of the M1 produces positive behavioral outcomes in PD animals and provides the basis for further clinical research examining the application of tDCS in patients with PD.

Structural plasticity of motor cortices assessed by voxel-based morphometry and immunohistochemical analysis following internal capsular infarcts in macaque monkeys.

Compensatory plastic changes in the remaining intact brain regions are supposedly involved in functional recovery following stroke. Previously, a compensatory increase in cortical activation occurred in the ventral premotor cortex (PMv), which contributed to the recovery of dexterous hand movement in a macaque model of unilateral internal capsular infarcts. Herein, we investigated the structural plastic changes underlying functional changes together with voxel-based morphometry (VBM) analysis of magnetic resonance imaging data and immunohistochemical analysis using SMI-32 antibody in a macaque model. Unilateral internal capsular infarcts were pharmacologically induced in 5 macaques, and another 5 macaques were used as intact controls for immunohistochemical analysis. Three months post infarcts, we observed significant increases in the gray matter volume (GMV) and the dendritic arborization of layer V pyramidal neurons in the contralesional rostral PMv (F5) as well as the primary motor cortex (M1). The histological analysis revealed shrinkage of neuronal soma and dendrites in the ipsilesional M1 and several premotor cortices, despite not always detecting GMV reduction by VBM analysis. In conclusion, compensatory structural changes occur in the contralesional F5 and M1 during motor recovery following internal capsular infarcts, and the dendritic growth of pyramidal neurons is partially correlated with GMV increase.

Differences in gait kinetics and kinematics between patients with rotating hinge knee and cruciate-retaining prostheses: a cross-sectional study.

[Purpose] Rotating hinge knee prostheses are often used in primary total knee arthroplasty. However, the biomechanics resulting from this treatment remain unexplored. This cross-sectional study compared patient data on gait kinetics and kinematics to assess the efficacy of primary total knee arthroplasty using a rotating hinge knee or other prostheses. [Participants and Methods] Thirty-three participants were assigned to the following groups: rotating hinge knee (n=7); cruciate-retaining prosthesis (n=7); untreated osteoarthritis (n=10); and young adults as a reference group (n=9). Participant data on biomechanical and spatiotemporal parameters were analyzed. [Results] The postoperative course of the rotating hinge knee group was not significantly longer than that of the cruciate-retaining prosthesis group. The knee varus angle and adduction moment of the rotating hinge knee group were significantly smaller than those of the untreated osteoarthritis group. Gait kinetics and kinematics were not different between the rotating hinge knee and cruciate-retaining prosthesis groups. [Conclusion] Participants who had undergone primary total knee arthroplasty with a rotating hinge knee prosthesis had worse preoperative conditions and demonstrated a similar postoperative gait as those who had undergone total knee arthroplasty with other prostheses. Our findings may be used to tailor rehabilitation programs for participants who have undergone total knee arthroplasty with a rotating hinge knee implant.

Tandem Gene Duplication of Dioxygenases Drives the Structural Diversity of Steroidal Glycoalkaloids in the Tomato Clade.

Cultivated tomato (Solanum lycopersicum) contains α-tomatine, a steroidal glycoalkaloid (SGA), which functions as a defense compound to protect against pathogens and herbivores; interestingly, wild species in the tomato clade biosynthesize a variety of SGAs. In cultivated tomato, the metabolic detoxification of α-tomatine during tomato fruit ripening is an important trait that aided in its domestication, and two distinct 2-oxoglutarate-dependent dioxygenases (DOXs), a C-23 hydroxylase of α-tomatine (Sl23DOX) and a C-27 hydroxylase of lycoperoside C (Sl27DOX), are key to this process. There are tandemly duplicated DOX genes on tomato chromosome 1, with high levels of similarity to Sl23DOX. While these DOX genes are rarely expressed in cultivated tomato tissues, the recombinant enzymes of Solyc01g006580 and Solyc01g006610 metabolized α-tomatine to habrochaitoside A and (20R)-20-hydroxytomatine and were therefore named as habrochaitoside A synthase (HAS) and α-tomatine 20-hydroxylase (20DOX), respectively. Furthermore, 20DOX and HAS exist in the genome of wild tomato S. habrochaites accession LA1777, which accumulates habrochaitoside A in its fruits, and their expression patterns were in agreement with the SGA profiles in LA1777. These results indicate that the functional divergence of α-tomatine-metabolizing DOX enzymes results from gene duplication and the neofunctionalization of catalytic activity and gene expression, and this contributes to the structural diversity of SGAs in the tomato clade.

Movement patterns of the functional reach test do not reflect physical function in healthy young and older participants.

The relationship of the Functional Reach Test (FRT) value with the Center of Pressure Excursion (COPE) and physical function remains unclear, and would be influenced by different population characteristics and movement patterns used in the FRT. Therefore, we explored the relationship between the FRT value and the COPE and physical function in healthy young and older individuals classified according to movement patterns. In 21 healthy young participants (42 sides) and 20 older participants (40 sides), three-dimensional motion analysis was performed during the FRT and physical function assessments. The participants were assigned to two clusters after performing a motion analysis during the FRT. Kinematic and kinetic parameters during the FRT and physical function assessment results were compared between the clusters for both groups. Correlation analysis was performed to investigate the relationships of the FRT value with COPE and physical function parameters in each cluster, in young and older individuals separately. The results showed that the hip strategies could be divided into two groups according to the degree of use (Small Hip Strategy, SHS Group; Large Hip Strategy, LHS Group). In the older SHS group, the FRT values were significantly correlated with the COPE (r = 0.75), toe grip strength (r = 0.62), and the five-times sit-to-stand test time (r = -0.52). In the older LHS group and in both groups of young individuals, there were no significant correlations of the FRT value with any parameters. The FRT value reflects the COPE and physical function only in older individuals using the SHS. This could explain previous discrepant results. As there is no simple relationship between the FRT value and physical function, it is important to include movement strategy assessment when using the FRT in clinical evaluations.

Tomato E8 Encodes a C-27 Hydroxylase in Metabolic Detoxification of α-Tomatine during Fruit Ripening.

Tomato (Solanum lycopersicum) contains α-tomatine, a steroidal glycoalkaloid that contributes to the plant defense against pathogens and herbivores through its bitter taste and toxicity. It accumulates at high levels in all the plant tissues, especially in leaves and immature green fruits, whereas it decreases during fruit ripening through metabolic conversion to the nontoxic esculeoside A, which accumulates in the mature red fruit. This study aimed to identify the gene encoding a C-27 hydroxylase that is a key enzyme in the metabolic conversion of α-tomatine to esculeoside A. The E8 gene, encoding a 2-oxoglutalate-dependent dioxygenase, is well known as an inducible gene in response to ethylene during fruit ripening. The recombinant E8 was found to catalyze the C-27 hydroxylation of lycoperoside C to produce prosapogenin A and is designated as Sl27DOX. The ripe fruit of E8/Sl27DOX-silenced transgenic tomato plants accumulated lycoperoside C and exhibited decreased esculeoside A levels compared with the wild-type (WT) plants. Furthermore, E8/Sl27DOX deletion in tomato accessions resulted in higher lycoperoside C levels in ripe fruits than in WT plants. Thus, E8/Sl27DOX functions as a C-27 hydroxylase of lycoperoside C in the metabolic detoxification of α-tomatine during tomato fruit ripening, and the efficient detoxification by E8/27DOX may provide an advantage in the domestication of cultivated tomatoes.

The biosynthetic pathway of potato solanidanes diverged from that of spirosolanes due to evolution of a dioxygenase.

Potato (Solanum tuberosum), a worldwide major food crop, produces the toxic, bitter tasting solanidane glycoalkaloids α-solanine and α-chaconine. Controlling levels of glycoalkaloids is an important focus on potato breeding. Tomato (Solanum lycopersicum) contains a bitter spirosolane glycoalkaloid, α-tomatine. These glycoalkaloids are biosynthesized from cholesterol via a partly common pathway, although the mechanisms giving rise to the structural differences between solanidane and spirosolane remained elusive. Here we identify a 2-oxoglutarate dependent dioxygenase, designated as DPS (Dioxygenase for Potato Solanidane synthesis), that is a key enzyme for solanidane glycoalkaloid biosynthesis in potato. DPS catalyzes the ring-rearrangement from spirosolane to solanidane via C-16 hydroxylation. Evolutionary divergence of spirosolane-metabolizing dioxygenases contributes to the emergence of toxic solanidane glycoalkaloids in potato and the chemical diversity in Solanaceae.

Time- and area-dependent macrophage/microglial responses after focal infarction of the macaque internal capsule.

We quantitatively investigated temporal changes of macrophages and microglia (MΦ/MG) after focal infarction of the internal capsule using a macaque model we recently established. Immunoreactivity for Iba1, a general marker for MΦ/MG, in the periinfarct core gradually increased from 0 days to 2-3 weeks after infarction, and the increased immunoreactivity continued at least until 6 months; no study in rodents has reported increased Iba1-immunoreactive cells for so long. Retrograde atrophy or degeneration of neurons in layer V of the primary motor cortex, where the descending motor tract originates, was seen as secondary damage. Here we found that Iba1-positive MΦ/MG transiently increased in layer V during several weeks after the infarction. Therefore, the time course of MΦ/MG activation differs between the perilesional area and the remote brain area where secondary damage occurs to tissue initially preserved after the infarct. Detailed analyses using the functional phenotype markers CD68, CD86, and CD206, as well as cytokines released by cells with each phenotype, suggest an anti-inflammatory role for activated MΦ/MG both in the periinfarct core during the chronic phase and in the primary motor cortex.

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity.

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional near-infrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fNIRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.

Identification of α-Tomatine 23-Hydroxylase Involved in the Detoxification of a Bitter Glycoalkaloid.

Tomato plants (Solanum lycopersicum) contain steroidal glycoalkaloid α-tomatine, which functions as a chemical barrier to pathogens and predators. α-Tomatine accumulates in all tissues and at particularly high levels in leaves and immature green fruits. The compound is toxic and causes a bitter taste, but its presence decreases through metabolic conversion to nontoxic esculeoside A during fruit ripening. This study identifies the gene encoding a 23-hydroxylase of α-tomatine, which is a key to this process. Some 2-oxoglutarate-dependent dioxygenases were selected as candidates for the metabolic enzyme, and Solyc02g062460, designated Sl23DOX, was found to encode α-tomatine 23-hydroxylase. Biochemical analysis of the recombinant Sl23DOX protein demonstrated that it catalyzes the 23-hydroxylation of α-tomatine and the product spontaneously isomerizes to neorickiioside B, which is an intermediate in α-tomatine metabolism that appears during ripening. Leaves of transgenic tomato plants overexpressing Sl23DOX accumulated not only neorickiioside B but also another intermediate, lycoperoside C (23-O-acetylated neorickiioside B). Furthermore, the ripe fruits of Sl23DOX-silenced transgenic tomato plants contained lower levels of esculeoside A but substantially accumulated α-tomatine. Thus, Sl23DOX functions as α-tomatine 23-hydroxylase during the metabolic processing of toxic α-tomatine in tomato fruit ripening and is a key enzyme in the domestication of cultivated tomatoes.

Functional near-infrared spectroscopy for monitoring macaque cerebral motor activity during voluntary movements without head fixation.

We developed an fNIRS system for monitoring macaque cerebral motor activity during voluntary movements without head fixation. fNIRS data at 27 channels in 7.5 mm spatial interval were calibrated by simulating light propagation through the macaque cranial tissues. The subject was instructed to repeatedly (75 times) retrieve a food pellet with alternating left or right hands from a food well for each session. We detected significant increases in oxygenated hemoglobin (Hb) and decrease in deoxygenated Hb in the primary motor area (M1) contralateral to the hand used. In more rostral and ventral regions in both hemispheres, the hemodynamic similarly changed regardless of used hand. Direct feeding to the mouth eliminated activity in the hand M1 whereas that at bilateral ventral regions (mouth M1 area) remained. Statistical analyses for the hemodynamics between left/right-hand use revealed the location of each hand M1 in either hemisphere. In these regions, the maximum amplitude and time of the maximum amplitude in the hemodynamic response evoked by food retrieval were highly correlated with the time associated with food retrieval. We could assign each channel to an appropriate functional motor area, providing proof of principle for future studies involving brain damage models in freely moving macaque monkeys.

Physical performance deterioration of temporary housing residents after the Great East Japan Earthquake.

Disaster has a negative impact on health conditions, especially on those of temporary housing residents. Health status has a close relationship with physical activity and performance. However, few reports have assessed physical performance among residents living in temporary housing. In this study, we compared physical capabilities between the elderly who evacuated to temporary housing and those who stayed in their own homes after the Great East Japan Earthquake. Subjects were recruited from those over 65 years of age who participated in the medical check-ups for temporary housing residents (TH group) or check-ups for residents of downtown areas (control group) in Soma City, Fukushima, in 2012. The subjects underwent grip strength, one-leg standing (OLS), and timed up and go tests (TUG). In total, 1890 participants were recruited. The TH group showed significantly stronger grip strength than that of the control group. On the other hand, the TH group showed weaker standing stability, according to decreased OLS and increased TUG scores. We revealed that standing stability was impaired among elderly temporary housing residents 1.5 years after the disaster. Disaster responders should take into account the health risks associated with living in temporary housing.