Programmed Cell Death Modifies Neural Circuits and Tunes Intrinsic Behavior.

Programmed cell death is a common feature of animal development. During development of the C. elegans hermaphrodite, programmed cell death (PCD) removes 131 cells from stereotyped positions in the cell lineage, mostly in neuronal lineages. Blocking cell death results in supernumerary "undead" neurons. We find that undead neurons can be wired into circuits, can display activity, and can modify specific behaviors. The two undead RIM-like neurons participate in the RIM-containing circuit that computes movement. The addition of these two extra neurons results in animals that initiate fewer reversals and lengthens the duration of those reversals that do occur. We describe additional behavioral alterations of cell-death mutants, including in turning angle and pharyngeal pumping. These findings reveal that, like too much PCD, too little PCD can modify nervous system function and animal behavior.

Influence of the Hawthorne effect on spatiotemporal parameters, kinematics, ground reaction force, and the symmetry of the dominant and nondominant lower limbs during gait.

The Hawthorne effect is a change in behavior resulting from awareness of being observed or evaluated. This study aimed to determine whether awareness of being evaluated or presence of an observer influence gait. Twenty-one young women were asked to walk in three conditions. In the first condition (unawareness of evaluation; UE), participants were aware that it was a practice trial, and there was no observer. In the second condition (awareness of evaluation; AE), participants were aware that their gait was being evaluated. The third condition (AE + researcher observation; RO) was similar to the second condition except that an additional researcher observed the participant' gait. The spatiotemporal, kinematic, ground reaction forces, and ratio index (symmetry of both lower limbs) were compared among the three conditions. A higher ratio index indicated a relative increase in the value on left versus right. Gait speed (P = 0.012) and stride length (right and left; P = 0.006 and 0.007, respectively) were significantly increased in the AE + RO than in UE. Range of motion of the right hip and left ankle was significantly greater in AE than in UE (P = 0.039 and 0.012, respectively). The ratio index of ground reaction force during push-off was significantly higher in AE and AE + RO conditions than in UE (P < 0.001 and P = 0.004, respectively). The Hawthorne effect (awareness of being evaluated or presence of an observer) potentially influences gait. Thus, factors that influence gait analysis should be considered when evaluating normal gait.

Comparing the Impact of Upper Body Control and Core Muscle Stabilization Training on Landing Biomechanics in Individuals with Functional Ankle Instability: A Randomized Controlled Trial.

Functional ankle instability (FAI), which is characterized by recurrent ankle sprains and perceived joint instability, arises from various factors contributing to compromised biomechanical control during activities, particularly those involving landing tasks. While current research predominantly addresses lower-extremity and core stabilization interventions for FAI, the contribution of upper body control to landing biomechanics in this population remains insufficiently explored. In this study, 42 participants (19 males, 23 females) with FAI were randomly assigned to either the upper-body control training group (UBCTG) or the core muscle stabilization training group (CMSTG). The groups underwent six-week interventions, with the UBCTG receiving a dynamic core exercise program including upper body control and the CMSTG receiving static core muscle training. Pre- and post-intervention assessments encompassed electromyography of the gastrocnemius, tibialis anterior, and peroneus longus, motion analysis of the lower extremities, and ground reaction force (GRF) readings during a single-leg-jump task. Additionally, dynamic balance was assessed using the Y balance test and self-reported measurements of ankle instability were performed. The results showed similar increases in muscle activation, joint movement, and self-reported ankle instability scores within both groups. However, significant between-group differences were observed in terms of knee flexion angle, dynamic balance, and ankle instability scores, favoring the UBCTG. Although the peak vertical GRF significantly decreased and the time to peak vertical GRF increased in both groups, more changes were noted in the UBCTG. Our results demonstrated that dynamic core exercises with additional upper body control training enhance landing biomechanics, dynamic balance, and stability in individuals with FAI. Consequently, we recommend incorporating shoulder girdle exercises, proprioceptive drills, and balance exercises into dynamic core training.

Effects of Augmented Reality Game-Based Cognitive-Motor Training on Restricted and Repetitive Behaviors and Executive Function in Patients with Autism Spectrum Disorder.

Restricted and repetitive behaviors (RRBs) and executive dysfunction are widely acknowledged as core features and hallmarks in patients with autism spectrum disorder (ASD). This study aimed to investigate the effects of augmented reality (AR) using motivational games with cognitive-motor exercises on RRBs, executive function (EF), attention, and reaction time in patients with ASD. Twenty-four patients (range from 6 to 18 years) diagnosed with ASD were recruited from local social welfare centers and randomly allocated to the AR game-based cognitive-motor training group (study group) or the conventional cognitive training group (control group). Both groups completed 30 min training sessions, twice a week for four weeks. Outcome measures were conducted before and after the intervention. As a result, improvements were observed in all the subscales of the RRBs in the study group except for self-injurious and ritualistic behavior. Significant improvements were observed in EF and reaction time in the study group, which was significantly higher compared to the control group. With the present findings, we can suggest that cognitive-motor training using AR game-based content generates positive effects on improving executive function reaction time and accuracy of responses and has a limited effect on RRBs in patients with ASD. This can be proposed as a complementary intervention associated with individualized daily management.

Effects of Augmented Reality-Based Dual-Task Program on Physical Ability by Cognitive Stage with Developmental Disabilities.

People diagnosed with developmental disabilities are less likely to participate in physical activities even if they are provided opportunities. This study aimed to examine the effects of dual-task exercise-based augmented reality (AR) on muscle strength, muscle endurance, balance ability, and flexibility among people with developmental disabilities. Twenty-seven patients with developmental disabilities were included in the study. The intervention was based on an AR-based rehabilitation program and lasted for 8 weeks. The results showed a statistically significant improvement in muscle strength, muscle endurance, balance ability, and flexibility after the intervention (p < 0.05). The AR-based dual-task program increased interest and motivation in the high-cognitive-stage groups, while less interest and motivation were observed in the low-cognitive-stage groups. Our results suggest that an AR-based dual-task program can be an effective method to improve physical ability in patients with high cognitive levels.

The Effect of Augmented Reality-Based Proprioceptive Training Program on Balance, Positioning Sensation and Flexibility in Healthy Young Adults: A Randomized Controlled Trial.

This study investigates whether Augmented Reality (AR)-based interventions can be as effective as physical therapists (PT) regarding balance, positioning sensation, and flexibility. A sample of 39 regular people who voluntarily participated in this study were randomly distributed into two groups. Then AR was applied in the experimental group and PT was applied in the control group. Variables were measured by Tetrax (static balance), Y-balance test (dynamic balance), CSMI (proprioception), and sit and reach test (flexibility). All measurements were analyzed using paired t-test and independent t-test. The exercise program of this study improved the stability index (ST) of the static balance in both groups after the intervention, and there was a significant difference (p < 0.05) at normal eye close (NC) and Pillow with eye close (PC) positions. Moreover, regarding the case of dynamic balance, there were significant differences in AR and PT groups to reach in all directions (p < 0.05). In the case of positioning sensation, there was no significant difference in both groups (p > 0.05), and there was a significant difference in flexibility (p < 0.05). When comparing the two groups, there was no significant difference in all categories (p > 0.05). As a result, AR can be considered an effective form of therapy and can be selected according to individual conditions.

Comparison of screw-home movement between patients with knee osteoarthritis and normal adults.

BACKGROUND: Tibial rotation accompanying sagittal movement contains the phenomenon of screw-home movement (SHM) of the knee, which plays an important role in knee stability during extension. OBJECTIVE: This study aimed to investigate the change of SHM in patients with knee osteoarthritis (OA). METHODS: Thirty-one sex-matched patients with knee OA and 31 normal subjects were recruited. The total tibial rotation was obtained during knee sagittal movement (extension and flexion) using an inertial measurement unit. The acquired angle of tibial rotation was divided into eight periods. The total tibial rotation and the variation of each period were compared between the OA and control groups. The difference in tibial rotation according to Kellgren-Lawrence (KL) grade was compared. RESULTS: The total tibial rotation of the OA group decreased compared with the control group during knee extension and flexion (P< 0.001). Variations of tibial rotation were significantly different between groups in all periods (P< 0.001) except for knee extension at 70∘ to 45∘ (P= 0.081). There was no significant difference in tibial rotations among the KA grades of OA patients. CONCLUSION: We found a reduction in the total tibial rotation and loss of the SHM in the unloaded OA knee. It could be predicted that reduced SHM appeared early in knee OA.

Effects of Caffeine Intake on Cardiopulmonary Variables and QT Interval after a Moderate-Intensity Aerobic Exercise in Healthy Adults: A Randomized Controlled Trial.

Caffeine is considered a widely consumed natural and legal psychoactive stimulant with several effects on the body. The present study attempted to investigate the effects of caffeine consumed before and after a physical exercise on cardiovascular and cardiorespiratory functions in healthy adults. 36 healthy adult males were recruited and randomly allocated to one of the three (3) groups: group I (exercise without caffeine consumption), group II (caffeine beverage intake before exercise), and group III (caffeine beverage intake immediately after exercise). The heart rate (HR), QTc interval, blood pressure (BP), respiratory rate (RR), oxygen consumption (VO2), and carbon dioxide emission (VCO2) were measured at 0, 5, 10, and 15 min after the exercise. We observed a significant difference in all measured outcomes during the different recovery times in all the groups (p < 0.05). HR, RR, SBP, VO2, and VCO2 gradually decreased with time, DBP contrarily increased with time, and the QTc showed an irregular pattern. We can affirm that ingestion of caffeine before and after moderate aerobic exercise slows down the parasympathetic stimulation, heart rate recovery, and the recovery of HR and QTc with no major effects on BP, RR, VO2, and VCO2 in healthy adult men.

Correlation of eccentric strength of the knee extensors and knee proprioception with dynamic postural control.

BACKGROUND: It is important for clinicians and researchers to perform dynamic postural control evaluation for predicting musculoskeletal conditions, injury prevention, and rehabilitation. OBJECTIVE: The purpose of this study was to investigate the relationship (1) between the eccentric strength of the knee extensors and star excursion balance test (SEBT), and (2) between the knee proprioception and SEBT. METHODS: Forty healthy young adults participated in this study. The eccentric peak torque (EPT) of the knee extensors, joint position sense, and force sense were measured. The participants also performed SEBT. Pearson's product-moment correlation and multiple linear regression analysis were used to determine the relationship between the variables and SEBT. RESULTS: The posteromedial direction of the SEBT was positively and strongly correlated with EPT (r= 0.74, P< 0.01). The anterior and posterolateral directions were positively and moderately correlated with EPT (r= 0.46, P< 0.01, and r= 0.69, P< 0.01, respectively.). However, knee proprioception was not correlated with all the directions of SEBT (P> 0.05). According to the results of multiple linear regression analysis, EPT of the knee extensors significantly predicted SEBT reach distances. CONCLUSION: The eccentric strength of the knee extensors seems to be an essential factor in dynamic postural control. However, the knee proprioception did not show a significant correlation with SEBT.

MON-2, a Golgi protein, mediates autophagy-dependent longevity in Caenorhabditis elegans.

The Golgi apparatus plays a central role in trafficking cargoes such as proteins and lipids. Defects in the Golgi apparatus lead to various diseases, but its role in organismal longevity is largely unknown. Using a quantitative proteomic approach, we found that a Golgi protein, MON-2, was up-regulated in long-lived Caenorhabditis elegans mutants with mitochondrial respiration defects and was required for their longevity. Similarly, we showed that DOP1/PAD-1, which acts with MON-2 to traffic macromolecules between the Golgi and endosome, contributed to the longevity of respiration mutants. Furthermore, we demonstrated that MON-2 was required for up-regulation of autophagy, a longevity-associated recycling process, by activating the Atg8 ortholog GABARAP/LGG-1 in C. elegans. Consistently, we showed that mammalian MON2 activated GABARAPL2 through physical interaction, which increased autophagic flux in mammalian cells. Thus, the evolutionarily conserved role of MON2 in trafficking between the Golgi and endosome is an integral part of autophagy-mediated longevity.

A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.

Insulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans, mutations in the daf-2/insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, and reproduction. Whether these pleiotropic effects can be dissociated at a specific step in insulin/IGF-1 signaling pathway remains unknown. Through performing a mutagenesis screen, we identified a missense mutation daf-18(yh1) that alters a cysteine to tyrosine in DAF-18/PTEN phosphatase, which maintained the long lifespan and enhanced immunity, while improving the reduced motility in adult daf-2 mutants. We showed that the daf-18(yh1) mutation decreased the lipid phosphatase activity of DAF-18/PTEN, while retaining a partial protein tyrosine phosphatase activity. We found that daf-18(yh1) maintained the partial activity of DAF-16/FOXO but restricted the detrimental upregulation of SKN-1/NRF2, contributing to beneficial physiological traits in daf-2 mutants. Our work provides important insights into how one evolutionarily conserved component, PTEN, can coordinate animal health and longevity.

C. elegans discriminates colors to guide foraging.

Color detection is used by animals of diverse phyla to navigate colorful natural environments and is thought to require evolutionarily conserved opsin photoreceptor genes. We report that Caenorhabditis elegans roundworms can discriminate between colors despite the fact that they lack eyes and opsins. Specifically, we found that white light guides C. elegans foraging decisions away from a blue-pigment toxin secreted by harmful bacteria. These foraging decisions are guided by specific blue-to-amber ratios of light. The color specificity of color-dependent foraging varies notably among wild C. elegans strains, which indicates that color discrimination is ecologically important. We identified two evolutionarily conserved cellular stress response genes required for opsin-independent, color-dependent foraging by C. elegans, and we speculate that cellular stress response pathways can mediate spectral discrimination by photosensitive cells and organisms-even by those lacking opsins.

Effect of trunk stabilization exercise on abdominal muscle thickness, balance and gait abilities of patients with hemiplegic stroke: A randomized controlled trial.

BACKGROUND: Trunk stability has been identified as an important prerequisite of functional movement. OBJECTIVE: To investigate the effectiveness of core muscle contraction training on abdominal muscle thickness, balance, and gait ability in stroke patients. METHODS: Thirty patients with stroke were randomly assigned to two experimental groups and a control group. All groups received conventional therapeutic exercise program for six weeks. The experimental groups additionally trained trunk stability exercise with abdominal hollowing or bracing maneuvers within training time. Primary outcome measures were evaluated abdominal muscle thickness using the sonography. Secondary outcome measures were evaluated by the Functional Reach Test (FRT), Berg Balance Scale (BBS), 10-meter walk test (10MWT), and Timed Up and Go test (TUG). RESULTS: Compared with the control group, the effect of trunk stability training for the experimental groups on the abdominal muscles thickness change was observed (p < 0.05). The values in balance and gait measures, BBS, FRT, 10MWT, and TUG, showed significant improvement after the intervention periods (p < 0.05), although no significant differences were found in scores of gait and balance scales among groups. CONCLUSIONS: Trunk stability training with selective abdominal muscles activation has beneficial effects on abdominal muscles, balance, and mobility in stroke patients. Our findings might provide support for introducing stroke rehabilitation.

Caenorhabditis elegans Lipin 1 moderates the lifespan-shortening effects of dietary glucose by maintaining ω-6 polyunsaturated fatty acids.

Excessive glucose causes various diseases and decreases lifespan by altering metabolic processes, but underlying mechanisms remain incompletely understood. Here, we show that Lipin 1/LPIN-1, a phosphatidic acid phosphatase and a putative transcriptional coregulator, prevents life-shortening effects of dietary glucose on Caenorhabditis elegans. We found that depletion of lpin-1 decreased overall lipid levels, despite increasing the expression of genes that promote fat synthesis and desaturation, and downregulation of lipolysis. We then showed that knockdown of lpin-1 altered the composition of various fatty acids in the opposite direction of dietary glucose. In particular, the levels of two ω-6 polyunsaturated fatty acids (PUFAs), linoleic acid and arachidonic acid, were increased by knockdown of lpin-1 but decreased by glucose feeding. Importantly, these ω-6 PUFAs attenuated the short lifespan of glucose-fed lpin-1-inhibited animals. Thus, the production of ω-6 PUFAs is crucial for protecting animals from living very short under glucose-rich conditions.

Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria.

The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria.

Mediator subunit MDT-15/MED15 and Nuclear Receptor HIZR-1/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans.

Zinc is essential for cellular functions as it is a catalytic and structural component of many proteins. In contrast, cadmium is not required in biological systems and is toxic. Zinc and cadmium levels are closely monitored and regulated as their excess causes cell stress. To maintain homeostasis, organisms induce metal detoxification gene programs through stress responsive transcriptional regulatory complexes. In Caenorhabditis elegans, the MDT-15 subunit of the evolutionarily conserved Mediator transcriptional coregulator is required to induce genes upon exposure to excess zinc and cadmium. However, the regulatory partners of MDT-15 in this response, its role in cellular and physiological stress adaptation, and the putative role for mammalian MED15 in the metal stress responses remain unknown. Here, we show that MDT-15 interacts physically and functionally with the Nuclear Hormone Receptor HIZR-1 to promote molecular, cellular, and organismal adaptation to cadmium and excess zinc. Using gain- and loss-of-function mutants and qRT-PCR and reporter analysis, we find that mdt-15 and hizr-1 cooperate to induce zinc and cadmium responsive genes. Moreover, the two proteins interact physically in yeast-two-hybrid assays and this interaction is enhanced by the addition of zinc or cadmium, the former a known ligand of HIZR-1. Functionally, mdt-15 and hizr-1 mutants show defective storage of excess zinc in the gut and are hypersensitive to zinc-induced reductions in egg-laying. Furthermore, mdt-15 but not hizr-1 mutants are hypersensitive to cadmium-induced reductions in egg-laying, suggesting potential divergence of regulatory pathways. Lastly, mammalian MDT-15 orthologs bind genomic regulatory regions of metallothionein and zinc transporter genes in a cadmium and zinc-stimulated fashion, and human MED15 is required to induce a metallothionein gene in lung adenocarcinoma cells exposed to cadmium. Collectively, our data show that mdt-15 and hizr-1 cooperate to regulate cadmium detoxification and zinc storage and that this mechanism is at least partially conserved in mammals.

MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.

Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.

The effect of therapeutic abdominal drawing-in maneuver using ultrasonography on lateral abdominal muscle thickness and balance.

BACKGROUND: Lateral abdominal muscles control the lumbar region and this manages the stability of the trunk through co-contraction. Abdominal drawing-in maneuver (ADIM) is the basis method for spine stabilization to restore proper neuromuscular control. OBJECTIVE: To investigate the effect of therapeutic abdominal drawing-in maneuver on abdominal muscle thickness and balance. METHODS: Twenty healthy adults were divided into 2 groups. The experimental group performed a bridging exercise with ADIM whereas the control group performed a bridging exercise without ADIM. The exercise was conducted 3 times a week for 4 weeks. Ultrasonography was used to measure the thickness of abdominal muscles. Balance ability was evaluated using Tetrax device. The Wilcoxon signed ranks test for comparison of pre and post values and Mann Whitney U test for comparison between groups were used. RESULTS: After 4 weeks, there was a significant difference in the thickness of TrA between groups (p< 0.05) whereas no significant difference in IO and EO (p> 0.05). In stability values, the experimental group showed significant changes in stability indexes of standing with eyes open (NO) and standing on the pillow with eyes closed (PC) after the exercise period and there was a significant difference in NO between two groups. CONCLUSIONS: Performing the bridging exercise with abdominal drawing-in maneuver is a more effective way to strengthen the abdominal muscles and stabilize the body than bridging exercise only.