Sex and stress interactions in fear synchrony of mouse dyads.

Socially coordinated threat responses support the survival of animal groups. Given their distinct social roles, males and females must differ in such coordination. Here, we report such differences during the synchronization of auditory-conditioned freezing in mouse dyads. To study the interaction of emotional states with social cues underlying synchronization, we modulated emotional states with prior stress or modified the social cues by pairing unfamiliar or opposite-sex mice. In same-sex dyads, males exhibited more robust synchrony than females. Stress disrupted male synchrony in a prefrontal cortex-dependent manner but enhanced it in females. Unfamiliarity moderately reduced synchrony in males but not in females. In dyads with opposite-sex partners, fear synchrony was resilient to both stress and unfamiliarity. Decomposing the synchronization process in the same-sex dyads revealed sex-specific behavioral strategies correlated with synchrony magnitude: following partners' state transitions in males and retroacting synchrony-breaking actions in females. Those were altered by stress and unfamiliarity. The opposite-sex dyads exhibited no synchrony-correlated strategy. These findings reveal sex-specific adaptations of socio-emotional integration defining coordinated behavior and suggest that sex-recognition circuits confer resilience to stress and unfamiliarity in opposite-sex dyads.

Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study.

Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association of the DNA methylation clock with cardiovascular diseases, cancer, and Alzheimer's disease, its relationship with kidney diseases remains largely unexplored. In particular, it is unclear whether the DNA methylation clock could serve as a predictor of worsening kidney function. In this pilot study involving 20 subjects, we investigated the association between the DNA methylation clock and subsequent deterioration of renal function. Additionally, we noninvasively evaluated DNA damage in urinary shedding cells using a previously reported method to examine the correlation with the DNA methylation clock and worsening kidney function. Our findings revealed that patients with an accelerated DNA methylation clock exhibited increased DNA damage in urinary shedding cells, along with a higher rate of eGFR decline. Moreover, in cases of advanced CKD (G4-5), the DNA damage in urinary shedding cells was significantly increased, highlighting the interplay between elevated DNA damage and eGFR decline. This study suggests the potential role of the DNA methylation clock and urinary DNA damage as predictive markers for the progression of chronic kidney disease.

Acute acalculous cholecystitis following extended administration of nirmatrelvir/ritonavir for persistent SARS-CoV-2 infection.

Immunocompromised patients with hematologic malignancies, particularly those treated with anti-CD20 antibodies such as rituximab and obinutuzumab, are known to be at risk of prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prolonged administration or combination therapy with antiviral medications reportedly yields favorable outcomes in these patients. However, knowledge regarding the adverse events associated with such therapeutic approaches is limited. Herein, we report a case of acute acalculous cholecystitis (AAC) following extended administration of nirmatrelvir/ritonavir (NMV/r) in a 68-year-old Japanese man with persistent SARS-CoV-2 infection. The patient had received obinutuzumab and bendamustine for follicular lymphoma and was diagnosed with coronavirus disease 2019 (COVID-19) approximately one year after treatment initiation with these drugs. Subsequently, he was admitted to a different hospital, where he received antiviral drugs, monoclonal antibodies, and steroids. Despite these interventions, the patient relapsed and was subsequently transferred to our hospital due to persistent SARS-CoV-2 infection. Remdesivir administration was ineffective, leading to the initiation of extended NMV/r therapy. One week later, he exhibited elevated gamma-glutamyl transpeptidase (GGT) levels, and one month later, he developed AAC. Cholecystitis was successfully resolved via percutaneous transhepatic gallbladder drainage and administration of antibiotics. We speculate that extended NMV/r administration, in addition to COVID-19, may have contributed to the elevated GGT and AAC. During treatment of persistent SARS-CoV-2 infection with extended NMV/r therapy, patients should be carefully monitored for the appearance of findings suggestive of biliary stasis and the development of AAC.

Viral uptake and pathophysiology of the lung endothelial cells in age-associated severe SARS-CoV-2 infection models.

Thrombosis is the major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the pathology of vascular endothelial cells (ECs) has received much attention. Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse-adapted SARS-CoV-2 virus strain in young and mid-aged mice. Only mid-aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA-Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid-aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis-related genes encoding PLAT, PF4, F3 PAI-1, and P-selectin were upregulated. In addition, the inflammation-related molecules such as CXCL2 and CXCL10 were upregulated in the mid-aged ECs upon viral infection. Our mouse model demonstrated that SARS-CoV-2 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation-related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age-associated EC response as a novel finding in human severe COVID-19.

Correlation between acylcarnitine/free carnitine ratio and cardiopulmonary exercise test parameters in patients with incident dialysis.

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis. Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20-90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio. Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO2) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO2 of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO2) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO2 (ß, -5.43 [95% confidence interval (CI), -10.15 to -0.70]) and percent-predicted peak VO2 (ß, -19.98 [95% CI, -38.43 to -1.52]) and with increased VE/VCO2 slope (ß, 13.76 [95% CI, 3.78-23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO2/delta WR, and chronotropic index. Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.

Effect of Arch Height Flexibility in Individuals With Flatfoot on Abductor Hallucis Muscle Activity and Medial Longitudinal Arch Angle During Short Foot Exercises.

Flatfoot presents decreased medial longitudinal arch (MLA), and such foot deformity involves intrinsic foot muscles dysfunction. Flatfoot can be classified into flexible and stiff types according to arch height flexibility (AHF). Short foot exercise (SFE) is an intrinsic foot muscle strengthening exercise, which is reportedly effective against flatfoot. However, its effectiveness against flexible or stiff types in flatfoot is unclear. We examined the effect of AHF in individuals with flatfoot during abductor hallucis muscle (AbH) activity and medial longitudinal arch during SFE. Foot alignment was assessed using the arch height index during standing, and individuals with flatfoot (N = 16) were recruited. The AbH activity and MLA angle during SFE while maintaining single-leg standing were assessed. The relationship between AHF and AbH activity and between AHF and MLA angle ratio was analyzed using correlation coefficients. Additional correlations between AHF and AbH activity were observed with the outliers removed. There were no correlations between AHF and AbH muscle activity and between AHF and MLA angle ratio. However, with the 2 outliers removed, moderate correlations between AHF and AbH activity were significant (r = 0.64, p = .01). AbH activity during SFE increased in individuals with flatfoot for high AHF (flexible type). Thus, SFE may be more effective for individuals with flatfoot having a high AHF. These findings may be helpful when making decisions for surgery and rehabilitation.

Social Synchronization of Conditioned Fear in Mice Requires Ventral Hippocampus Input to the Amygdala.

BACKGROUND: Social organisms synchronize behaviors as an evolutionary-conserved means of thriving. Synchronization under threat, in particular, benefits survival and occurs across species, including humans, but the underlying mechanisms remain unknown because of the scarcity of relevant animal models. Here, we developed a rodent paradigm in which mice synchronized a classically conditioned fear response and identified an underlying neuronal circuit. METHODS: Male and female mice were trained individually using auditory fear conditioning and then tested 24 hours later as dyads while allowing unrestricted social interaction during exposure to the conditioned stimulus under visible or infrared illumination to eliminate visual cues. The synchronization of the immobility or freezing bouts was quantified by calculating the effect size Cohen's d for the difference between the actual freezing time overlap and the overlap by chance. The inactivation of the dorsomedial prefrontal cortex, dorsal hippocampus, or ventral hippocampus was achieved by local infusions of muscimol. The chemogenetic disconnection of the hippocampus-amygdala pathway was performed by expressing hM4D(Gi) in the ventral hippocampal neurons and infusing clozapine N-oxide in the amygdala. RESULTS: Mice synchronized cued but not contextual fear. It was higher in males than in females and attenuated in the absence of visible light. Inactivation of the ventral but not dorsal hippocampus or dorsomedial prefrontal cortex abolished fear synchronization. Finally, the disconnection of the hippocampus-amygdala pathway diminished fear synchronization. CONCLUSIONS: Mice synchronize expression of conditioned fear relying on the ventral hippocampus-amygdala pathway, suggesting that the hippocampus transmits social information to the amygdala to synchronize threat response.

The Effect of Ankle Position on Peak Eccentric Force during The Nordic Hamstring Exercise.

Peak eccentric force during the Nordic hamstring exercise (NHE) is recognized as a predictive factor for hamstring strain injury (HSI). During the NHE, the knee flexor muscles are eccentrically contracting to resist the knee joint extension. Therefore, it is thought that the action of the gastrocnemius muscle, and thus the ankle position, influences peak eccentric force during the NHE. However, the effect of ankle position on peak eccentric force during the NHE remains unclear. Therefore, we investigated the effect of ankle position on peak eccentric force during the NHE in a cohort of 50 healthy young male rugby players (mean age, 18.7 ± 1.2 years; mean body mass, 81.7 ± 15.2 kg; height, 1.72 ± 0.06 m) with no history of HSI. Each participant performed NHE strength testing with the ankle dorsiflexed or plantarflexed position and was instructed to fall forward as far as possible within 3 s. Peak eccentric force, reported relative to body mass (N/kg), of both legs was recorded, and the mean values of both legs were compared in both ankle positions. The mean peak eccentric force was significantly greater with the ankle plantarflexed position than the dorsiflexed position (3.8 ± 1.1 vs. 3.5 ± 1.1 N/kg, respectively, p = 0.049). These results indicate that ankle position should be carefully considered when measuring peak eccentric force during the NHE and performing NHE training.

Dual emission from an iridium(III) complex/counter anion ion pair.

[Ir(tpy)2](PF6)3 (tpy = 2,2':6',2''-terpyridine) dissolved in CH3CN was found to exhibit dual color luminescent emission depending on the excitation wavelength. Specifically, blue and green emissions were obtained with excitation at 350 and 410 nm, respectively. Because the associated emission spectra were consistent with those of [Ir(tpy)2]Cl3 in water and [Ir(tpy)2](PF6)3 in the crystalline state, respectively, this dual emission is attributed to emissions from the [Ir(tpy)2]3+ cation and its ion pair [Ir(tpy)2]3+·PF6-. The emission is assigned to the 3π-π* transition of the ligands based on time-dependent density functional theory (TD-DFT) calculations. Conversely, [Ir(tpy)2]I3 in CH3CN shows emission due to [Ir(tpy)2]3+ but not [Ir(tpy)2]3+·I-, while crystalline [Ir(tpy)2]I3 emits red luminescence at 77 K that is inconsistent with that from [Ir(tpy)2]3+. Since the emission energies of crystalline [Ir(tpy)2]X3 (X- = Cl-, Br- or I-) show a good correlation with the electron affinity of X, the emissions are assigned to a counter anion to complex ion charge-transfer transition. This hypothesis is supported by TD-DFT calculations regarding [Ir(tpy)2]3+·X-.

Disinhibition-assisted long-term potentiation in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons.

Significance: Natural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High- and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression. This approach is effective in many brain areas but not in the basolateral amygdala (BLA) because the robust local GABAergic tone inside BLA restricts synaptic plasticity. Aim: We aimed at identifying the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Approach: Chemogenetic or optogenetic suppression of specific GABAergic neurons in BLA was combined with high-frequency stimulation of the BLA afferents as a method for LTP induction. Results: Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses, both ex vivo and in vivo. Conclusions: These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.

Differences in muscle attachment proportion within the most common location of medial tibial stress syndrome in vivo.

INTRODUCTION: The medial tibial stress syndrome is one of the most common causes of running-related injuries. The primary study objective was to observe the attachment proportion of flexor digitorum longus and soleus, at the most common location of medial tibial stress syndrome, using ultrasonography, on a large cohort of young males and females to evaluate for gender-based anatomical differences. The secondary objective of this study was to investigate the relationship between the anatomical features and medial tibial stress syndrome. METHODS: In this study, we observed whether or not flexor digitorum longus and/or soleus attached at the middle and distal thirds of the medial margin of the tibia (most common location of medial tibial stress syndrome) using ultrasonography. History of medial tibial stress syndrome was defined by inquiries. RESULTS: The Chi2 tests showed that the attachment proportion of the soleus in female participants was significantly higher than that observed in male participants. In addition, Chi2 testing showed that there were no significant differences between attachment proportion of soleus of legs with history of medial tibial stress syndrome and legs without history of medial tibial stress syndrome, in both male and female participants. CONCLUSIONS: These results suggested that the anatomical features of flexor digitorum longus might be involved in medial tibial stress syndrome development, whereas the anatomical features of the soleus might not be involved in medial tibial stress syndrome development. LEVEL OF EVIDENCE: III, cross-sectional study.

A retrospective study of mechanisms of anterior cruciate ligament injuries in high school basketball, handball, judo, soccer, and volleyball.

The purpose of this study was to analyze the mechanism of anterior cruciate ligament (ACL) injuries among male and female high school students across several different sports to understand ACL injury trends.A total of 1000 cases involving high school students who suffered ACL injuries during school activities (soccer, basketball, volleyball, handball, and judo) and who received insurance benefits through the Injury and Accident Mutual Aid Benefit System, were included to clarify the various mechanisms of ACL injuries. The mechanism of ACL injury was divided into contact and non-contact injuries. Contact injuries were further divided into direct and indirect contact injuries. Non-contact ACL injuries were also further divided into landing injuries, which involved jump-landing movements, and cutting and stopping injuries, which involved movement with a change of direction and deceleration.Overall, 99.0% of judo ACL injuries were categorized as contact ACL injuries. With regards to ball sports, the number of non-contact ACL injuries among basketball, volleyball, and handball players was significantly higher than the number of contact injuries (67.0%, 86.5%, and 68.5% respectively). With regards to female soccer and basketball players, the number of indirect ACL injuries was higher than direct injuries (72.2% and 76.7%, respectively).Volleyball was associated with a higher rate of non-contact injuries. Soccer, basketball, and handball were associated with more or similar rates of indirect and non-contact injuries than direct injuries. Judo was associated with a higher rate of contact injuries.

Quantitative evaluation method for clarifying ankle plantar flexion angles using anterior drawer and inversion stress tests: a cross-sectional study.

BACKGROUND: Chronic ankle instability (CAI) may result from repeated, frequent ankle sprains during sports activities. Manual examination for CAI is conducted; however, quantitative methods for the evaluation of CAI have not been established, and the reproducibility of the amount of stress is low. This cross-sectional study aimed to use a stress device and ultrasound for the quantitative evaluation of the change in the length of the anterior talofibular ligament (ATFL) during simulated anterior drawer and ankle inversion stress tests. METHODS: Questionnaires were provided to 160 healthy college students (86 men, 74 women; 320 ankles). We extracted two groups from them: control subjects without a history of ankle injury (n = 64 ankles) and subjects with CAI (n = 54 ankles). We calculated the change in the length of the ATFL with anterior drawer and inversion stress tests at ankle joint plantar flexions of 0°, 20°, and 45° using ultrasound images. RESULTS: The anterior length change rates were significantly higher in the CAI group than in the control group at ankle joint plantar flexions of 20° and 45° in men (P < 0.05). The inversion length change rates were significantly higher in the CAI group at ankle joint plantar flexion of 20° in men (P < 0.05). No significant between-group difference in the anterior and inversion length change rates was observed in women. CONCLUSIONS: Stress ultrasound revealed greater length changes in the ATFL in the CAI group than in the control group. The stress test may be useful at ankle joint plantar flexion of 20° for men.

Relationships between differences in the number of fiber bundles of the anterior talofibular ligament and differences in the angle of the calcaneofibular ligament and their effects on ankle-braking function.

PURPOSE: The aim was to clarify the relationships between differences in the number of fiber bundles of the anterior talofibular ligament (ATFL) and differences in the angle of the calcaneofibular ligament (CFL) with respect to the long axis of the fibula and their effects on ankle braking function. METHODS: The study sample included 110 Japanese cadavers. ATFLs were categorized as: Type I with one fiber bundle; Type II with two fiber bundles with incomplete separation and complete separation; and Type III with three fiber bundles. The CFLs were categorized according to the angles of the CFLs with respect to the long axis of the fibula and the number of fiber bundles. Six categories were established: CFL10° (angle of the CFL with respect to the long axis of the fibula from 10° to 19°); CFL20° (range 20°-29°); CFL30° (range 30°-39°); CFL40° (range 40°-49°); CFL50° (range 50°-59°); and CFL2 (CFLs with two crossing fiber bundles). RESULTS: ATFL was Type I in 34 legs (31%), Type II in 66 legs (60%), and Type III in 10 legs (9%). Five CFL categories were identified: CFL10° in 4 feet (3.7%); CFL20° in 23 feet (20.9%); CFL30° in 34 feet (30.9%); CFL40° in 33 feet (30%); CFL50° in 15 feet (13.6%); and CFL2 in one foot (0.9%). Type III contained mainly CFL40° and CFL50° (7 of 10 feet). CONCLUSIONS: ATFL and CFL appear to cooperate in the ankle joint braking function.

The relationships between the quadratus plantae and the flexor digitorum longus and the flexor hallucis longus.

PURPOSE: The purpose of this research was to clarify the relationships between quadratus plantae (QP) and flexor digitorum longus (FDL) and flexor hallucis longus (FHL) using large-scale specimens. METHODS: This study examined 116 legs from 62 Japanese cadavers. The QP was classified as: Type I, formed by the lateral and medial heads; Type II, the lateral head is absent; and Type III, the medial head is absent. The FHL branches to the lesser toes were classified as: Type A, connection from FHL to toe 2; Type B, connection from FHL to toes 2 and 3; Type C, connection from FHL to toes 2-4. Next, the relationships between QP and FHL and FDL were observed. RESULTS: Type I accounted for 87%, Type II for 10%, and Type III for 3%. Type A accounted for 33%, Type B for 53%, and Type C for 14%. Regarding the relationship between QP and FDL, regardless of the classification of the connections of the FHL tendon slip to the lesser toes, QP attachments to FDL branching to toes 2, 3, and 4 were seen in 47-59%. Furthermore, QP attachments to FDL branching to toes 2, 3, 4, and 5 were seen in 41-47%. CONCLUSIONS: QP appears to function strongly to counter the oblique pull of FDL and FHL and as a lesser digit plantar flexor.

Spinal reciprocal inhibition in the co-contraction of the lower leg depends on muscle activity ratio.

The spinal reciprocal inhibition during co-contraction remains unclear. Reports on the reciprocal Ia and D1 inhibitions in the co-contraction are lacking, and a point about the muscle activity amount during co-contraction is unclear. This study aimed to clarify the influence of changes in the ratio of soleus (Sol) and tibialis anterior (TA) muscle activities in co-contraction on reciprocal Ia and D1 inhibitions. Twenty healthy adults were subjected to four stimulatory conditions: a conditioning stimulus-test stimulation interval (CTI) of - 2, 2, or 20 ms or a test stimulus without a conditioning stimulus (single). Co-contraction [change in (Sol)/(TA) activity] was examined at task A, 0%/0% maximal voluntary contraction (MVC); task B, 5%/5% MVC; task C, 15%/15% MVC; task D, 5%/15% MVC; and task E, 15%/5% MVC. At 2-ms CTI, the H-reflex amplitude value was significantly lower in tasks A, B, C, and D than in the single condition. Among the tasks, the H-reflex amplitude values were lower for A, B, C, and D than for E. At 20-ms CTI, the H-reflex amplitude was significantly lower in tasks A, B, C, D, and E. Among the tasks, the H-reflex amplitude was significantly lower from task A and B to task E. The change in the muscle activity ratio during co-contraction could modulate reciprocal Ia inhibition depending on the Sol/TA muscle activity ratio. D1 inhibition at rest did not differ significantly when the Sol/TA ratio was equal or when TA muscle activity was high. During co-contraction with high Sol muscle activity, D1 inhibition decreased from rest.

Prefrontal-amygdala plasticity enabled by observational fear.

Observing fear in others (OF) is a form of social stress. In mice, it enhances inhibitory avoidance learning and causes the formation of silent synapses in the prefrontal-amygdala pathway. Here, we report that OF made that pathway prone to facilitation both ex vivo and in vivo. Ex vivo, OF enabled induction of long-term potentiation (LTP), expressed mostly postsynaptically and occluded by inhibitory avoidance training. In vivo, OF enabled facilitation of the dmPFC-BLA pathway by inhibitory avoidance training. The facilitation persisted during the first 4 h after the training when the prefrontal cortex and amygdala are involved in memory consolidation. Thus, the OF-generated silent synapses likely enable plasticity that may enhance the consolidation of inhibitory avoidance memories.

Differences in the strain applied to Achilles tendon fibers when the subtalar joint is overpronated: a simulation study.

PURPOSE: The purpose of this study was to investigate the strain applied to each of the tendon fiber bundles of the medial head of the gastrocnemius (MG), the lateral head of the gastrocnemius (LG), and the soleus muscle (Sol) that compose the Achilles tendon (AT) when the subtalar joint is pronated and supinated. METHODS: Three AT twist types (least, moderate, extreme) were investigated. Using the MicroScribe system, the AT and the talocrural and subtalar joints were digitized to reconstruct three-dimensional models. Using this system, subtalar joint rotations in the pronation (20°) and supination (20°) directions were simulated, and the degrees of strain (%) on each tendon were calculated. RESULTS: For all twist types, when the subtalar joint was pronated, MG, LG, and Sol stretched, and when supinated, MG, LG, and Sol shortened. In particular, the least and severe twist types had large degrees of strain of Sol when the subtalar joint was pronated, and furthermore, each tendon fiber composing Sol had different degrees of strain. CONCLUSIONS: The study results suggest that the degree of strain applied within the AT with subtalar joint pronation is not constant, and that, especially in least and extreme twist types, the risk of developing AT disorders may increase.

Social modulation of fear: Facilitation vs buffering.

Social behaviors largely constitute mutual exchanges of social cues and the responses to them. The adaptive response also requires proper interpretation of the current context. In fear behaviors, social signals have bidirectional effects-some cues elicit or enhance fear whereas other suppress or buffer it. Studies on the social facilitation and social buffering of fear provide evidence of competition between social cues of opposing meanings. Co-expression of opposing cues by the same animal may explain the contradicting outcomes from the interaction between naive and frightened conspecifics, which reflect the fine balance between fear facilitation and buffering. The neuronal mechanisms that determine that balance provide an exciting target for future studies to probe the brain circuits underlying social modulation of emotional behaviors.

Impaired social contacts with familiar anesthetized conspecific in CA3-restricted brain-derived neurotrophic factor knockout mice.

Familiarity is conveyed by social cues and determines behaviors toward conspecifics. Here, we characterize a novel assay for social behaviors in mice-contacts with anesthetized conspecific-which eliminates reciprocal interactions, including intermale aggression and shows behaviors that are independent of the demonstrator's activity. During the initial 10 minutes (phase-1), the wild-type (WT) subjects contacted the anesthetized conspecifics vigorously regardless of familiarity. During the subsequent 80 minutes (phase-2), however, they contacted more with familiar than unfamiliar conspecifics. We then applied this test to highly aggressive mice with a hippocampal CA3-restricted knockout (KO) of brain-derived neurotrophic factor (BDNF), in which aggression may mask other social behaviors. The KO mice showed less preference for contacting familiar conspecifics than did WT mice during phase-2 but no differences during phase-1. Among nonsocial behaviors, WT mice also spent less time eating in the presence of familiar than with unfamiliar conspecifics, which was not seen in KO mice. In addition, KO mice exhibited reduced pain sensitization. Altogether, these findings suggest that CA3-specific deletion of BDNF results in deficits in circuits that process social cues from familiar conspecifics as well as pain and may underlie empathy-like behaviors.