Novel Avian Influenza A(H5N6) Virus in Wild Birds, South Korea, 2023.

We isolated novel reassortant avian influenza A(H5N6) viruses containing genes from clade 2.3.4.4b H5N1 virus and low pathogenicity avian influenza viruses in carcasses of whooper swans and bean geese in South Korea during December 2023. Neuraminidase gene was from a clade 2.3.4.4b H5N6 virus infecting poultry and humans in China.

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides.

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs.

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.

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat.

Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.

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.

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.

Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling.

Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP-60/HSPD1, a major mitochondrial chaperone, boosts anti-bacterial immunity through the up-regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP-60 is necessary and sufficient to increase resistance to PA14. We show that HSP-60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti-bacterial immune pathway, is down-regulated by genetic inhibition of hsp-60, and up-regulated by increased expression of hsp-60 Overexpression of HSPD1, the mammalian ortholog of hsp-60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol-localized HSP-60 physically binds and stabilizes SEK-1/MAP kinase kinase 3, which in turn up-regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up-regulating cytosolic p38 MAPK signaling.

The role of dietary carbohydrates in organismal aging.

Carbohydrates are essential nutrients that are used as a primary source of energy. Carbohydrate utilization should be properly controlled, as abnormal regulation of carbohydrate metabolism is associated with diseases, such as diabetes, cardiovascular diseases, and stroke. These metabolic syndromes have become a serious problem in developed countries, and there is an increased need for research examining the influence of carbohydrates on animal physiology. Diets enriched in glucose, a major carbohydrate, are also associated with accelerated aging in several model organisms, including yeast and Caenorhabditis elegans (C. elegans). Genetic factors that mediate the effects of high glucose diets on aging have been identified during the last decade, mostly through the use of C. elegans. In this review, we describe studies that determine the effects of carbohydrate-enriched diets on aging by focusing on the mechanisms through which evolutionarily conserved pathways mediate the lifespan-altering effects of glucose in C. elegans. These include the insulin/insulin-like growth factor-1, sterol-regulatory element-binding protein, and AMP-activated protein kinase signaling pathways. We also discuss the effects of various carbohydrates and carbohydrate-derived metabolites on aging in model organisms and cultured mammalian cells. Finally, we discuss how dietary carbohydrates influence health and aging in humans.

Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans.

Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS.

The effects of pelvic diagonal movements and resistance on the lumbar multifidus.

[Purpose] The purpose of this study was to compare the effects of pelvic diagonal movements, made with and without resistance, on the thickness of lumbar multifidus muscles. [Subjects and Methods] Participants in this study were healthy subjects who had no musculoskeletal disorders or lumbar-related pain. Participants were positioned on their side and instructed to lie with their hip flexor at 40 degrees. Ultrasonography was used for measurement, and the values of two calculations were averaged. [Results] The thickness of ipsilateral lumbar multifidus muscles showed a significant difference following the exercise of pelvic diagonal movements. The results of anterior elevation movements and posterior depression movements also demonstrated significant difference. There was no significant difference in lumbar multifidus muscles thickness between movements made with and without resistance. [Conclusion] These findings suggest that pelvic diagonal movements can be an effective method to promote muscular activation of the ipsilateral multifidus. Furthermore, researchers have concluded that resistance is not required during pelvic diagonal movements to selectively activate the core muscles.

Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

Effects of adjustment of transcranial direct current stimulation on motor function of the upper extremity in stroke patients.

[Purpose] The purpose of this study was to examine the effects of transcranial direct current stimulation (tDCS) applied to the cerebral cortex motor area on the upper extremity functions of hemiplegic patients. [Subjects and Methods] Twenty four Patients with hemiplegia resulting from a stroke were divided into two groups: a tDCS group that received tDCS and physical therapy and a control group that received only physical therapy. A functional evaluation of the two groups was performed, and an electrophysiological evaluation was conducted before and after the experiment. Statistical analyses were performed to verify differences before and after the experiment. All statistical significance levels were set at 0.05. [Results] The results showed that functional evaluation scores for the elbow joint and hand increased after the treatment in both the experimental group and the control group, and the increases were statistically significantly different. [Conclusion] tDCS was effective in improving the upper extremity motor function of stroke patients. Additional research is warranted on the usefulness of tDCS in the rehabilitation of stroke patients in the clinical field.

Effects of fast and slow squat exercises on the muscle activity of the paretic lower extremity in patients with chronic stroke.

[Purpose] The purpose of this study was to investigate the effects of the speed of squat exercises on paretic lower extremity muscle activity in patients with hemiplegia following a stroke. [Subjects and Methods] Ten stroke patients performed fast and slow squat exercises for 2 seconds and 8 seconds, respectively. The muscle activities of the paretic and non-paretic sides of the rectus femoris muscle, the biceps femoris muscle, and the tibialis anterior muscle were assessed and compared using surface electromyography. [Results] The paretic side of the rectus femoris muscle showed statistically significant differences in the fast squat exercise group, which demonstrated the highest muscle activity during the rapid return to the upright position. [Conclusion] The rectus femoris muscle showed the highest muscle activity during the return to the upright position during the fast squat exercise, which indicates that the rectus femoris muscle is highly active during the fast squat exercise.

Effects of visibility and types of the ground surface on the muscle activities of the vastus medialis oblique and vastus lateralis.

[Purpose] The purpose of this study was to compare the effects of visibility and types of ground surface (stable and unstable) during the performance of squats on the muscle activities of the vastus medialis oblique (VMO) and vastus lateralis (VL). [Subjects and Methods] The subjects were 25 healthy adults in their 20s. They performed squats under four conditions: stable ground surface (SGS) with vision-allowed; unstable ground surface (UGS) with vision-allowed; SGS with vision-blocked; and UGS with vision-blocked. The different conditions were performed on different days. Surface electromyogram (EMG) values were recorded. [Results] The most significant difference in the activity of the VMO and VL was observed when the subjects performed squats on the UGS, with their vision blocked. [Conclusion] For the selective activation of the VMO, performing squats on an UGS was effective, and it was more effective when subjects' vision was blocked.

Effects of water-table changes following rainfall events on arsenic fate and transport in groundwater-surface water mixing zones.

This study investigated the effects of groundwater-surface water (GW-SW) interactions on the fate and transport of arsenic (As) following rainfall events and subsequent water-table changes in GW-SW mixing zones, comprising the riparian and hyporheic zones, near an abandoned gold mine. During the dry and wet periods, stream conditions changed from flow-through to gaining, respectively. Water-table changes caused by rainfall events controlled flow paths between riparian zones and the stream, affecting spatiotemporal variation in the redox and pH conditions of the aquatic environment. Subsequently, the fate and transport of As in GW-SW mixing zones was responsive to variations in redox and pH conditions. Through the oxidative dissolution of As-bearing sulfide minerals and the reductive dissolution of iron (Fe) oxides with adsorbed As, As was released into the groundwater in the riparian zones and transported to the stream and streambed along the baseflow discharge. However, As was also immobilized in the sediment through adsorption onto Fe-oxides and coprecipitation with calcium (Ca) and zinc (Zn), suggesting that the sediment acts as a sink-and-source of As in aquatic environments. Therefore, water-table changes and GW-SW interactions could play an important role in the fate and transport of As in aquatic environments, specifically groundwater-riparian-streambed-stream systems. The findings of this study will provide scientific insights into the mechanisms of As in aquatic environments, aiding in improved decision-making to ensure safe and sustainable water management in response to future climate change.

The effects of a warm whirlpool bath on pain and stiffness of patients with chronic stroke induced knee osteoarthritis.

[Purpose] This study set out to investigate the effects of leg immersion in warm water on pain, and stiffness of patients with stroke-induced chronic osteoarthritis. [Subjects] Forty-four patients with chronic stroke were randomly assigned to either the whirlpool group (n=24) or the control group (n=20). [Methods] Subjects in the whirlpool group immersed their legs in a whirlpool bath at 40 °C for 40 minutes 5 times a week for 8 weeks. The control group of patients was instructed to perform activities as usual without using a whirlpool bath. Pre-immersion and post-immersion measurements of the Western Ontario and McMaster University arthritis index (WOMAC)-pain and stiffness indexes were compared to determine the effects of the intervention. The paired t-test was performed to test the significance of differences before and after the experiment. The independent t-test was conducted in order to test the significance of differences between the whirlpool and control groups. Statistical significance was accepted for values of p<0.05. [Results] The WOMAC-pain score, and stiffness index were significantly lower after the intervention. [Conclusion] Immersion of the lower extremities in a whirlpool bath was beneficial for patients with chronic stroke-induced knee osteoarthritis.

The relationship of abdominal muscles balance and body balance.

This study aimed to identify what impact the thickness differences between the leftside and rightside transversus abdominis (TrA), internal obliquus (IO) and external obliquus (EO) have on balance ability in the abdominal drawing-in maneuver (ADIM) and resting postures. [Subjects and Methods] In this study, 41 young adults were asked to adopt a resting posture and to perform ADIM. The thicknesses of the abdominal muscles (TrA, IO, EO) were measured using ultrasound imaging, Then balance ability was measured, so that a comparative analysis could be carried out. [Results] According to the results, the thicknesses of TrA and IO very significantly increased when ADIM was performed. The changes in thickness of the muscles on the left and right sides showed no significant correlations with balance ability. [Conclusion] According to the study results, the difference in thickness between the left and right side muscles in a normal person is small (symmetric), and the differences in the thickness of TrA and IO on the left and right side reduced when the ADIM, which is a re-education method for abdominal muscles was performed. Therefore, we consider that the ADIM should be used in future clinical trials to induce symmetric contraction of the abdominal muscles. Also, the correlation results of muscle balance and body balance can be used as empirical data.

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.

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.