Assessment and modelling of the activation-dependent shift in optimal length of the human soleus muscle in vivo.

Previous in vitro and in situ studies have reported a shift in optimal muscle fibre length for force generation (L0) towards longer length at decreasing activation levels (also referred to as length-dependent activation), yet the relevance for in vivo human muscle contractions with a variable activation pattern remains largely unclear. By a combination of dynamometry, ultrasound and electromyography (EMG), we experimentally obtained muscle force-fascicle length curves of the human soleus at 100%, 60% and 30% EMGmax levels from 15 participants aiming to investigate activation-dependent shifts in L0 in vivo. The results showed a significant increase in L0 of 6.5 ± 6.0% from 100% to 60% EMGmax and of 9.1 ± 7.2% from 100% to 30% EMGmax (both P < 0.001), respectively, providing evidence of a moderate in vivo activation dependence of the soleus force-length relationship. Based on the experimental results, an approximation model of an activation-dependent force-length relationship was defined for each individual separately and for the collective data of all participants, both with sufficiently high accuracy (R2 of 0.899 ± 0.056 and R2 = 0.858). This individual approximation approach and the general approximation model outcome are freely accessible and may be used to integrate activation-dependent shifts in L0 in experimental and musculoskeletal modelling studies to improve muscle force predictions. KEY POINTS: The phenomenon of the activation-dependent shift in optimal muscle fibre length for force generation (length-dependent activation) is poorly understood for human muscle in vivo dynamic contractions. We experimentally observed a moderate shift in optimal fascicle length towards longer length at decreasing electromyographic activity levels for the human soleus muscle in vivo. Based on the experimental results, we developed a freely accessible approximation model that allows the consideration of activation-dependent shifts in optimal length in future experimental and musculoskeletal modelling studies to improve muscle force predictions.

Spatiotemporal modulation of a common set of muscle synergies during unpredictable and predictable gait perturbations in older adults.

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed steps and the recovery steps. Sixty-three healthy older adults (71.2±5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (P<0.05). These modifications were observed for up to four recovery steps and were more pronounced (P<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may improve the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.

Personalized tendon loading reduces muscle-tendon imbalances in male adolescent elite athletes.

An imbalanced adaptation of muscle strength and tendon stiffness in response to training may increase tendon strain (i.e., the mechanical demand on the tendon) and consequently tendon injury risk. This study investigated if personalized tendon loading inducing tendon strain within the effective range for adaptation (4.5%-6.5%) can reduce musculotendinous imbalances in male adolescent handball athletes (15-16 years). At four measurement time points during a competitive season, we assessed knee extensor muscle strength and patellar tendon mechanical properties using dynamometry and ultrasonography and estimated the tendon's structural integrity with a peak spatial frequency (PSF) analysis of proximal tendon ultrasound scans. A control group (n = 13) followed their usual training routine, an intervention group (n = 13) integrated tendon exercises into their training (3x/week for ~31 weeks) with a personalized intensity corresponding to an average of ~6.2% tendon strain. We found a significant time by group interaction (p < 0.005) for knee extensor muscle strength and normalized patellar tendon stiffness with significant increases over time only in the intervention group (p < 0.001). There were no group differences or time-dependent changes in patellar tendon strain during maximum voluntary contractions or PSF. At the individual level, the intervention group demonstrated lower fluctuations of maximum patellar tendon strain during the season (p = 0.005) and a descriptively lower frequency of athletes with high-level tendon strain (≥9%). The findings suggest that the personalized tendon loading program reduced muscle-tendon imbalances in male adolescent athletes, which may provide new opportunities for tendon injury prevention.

Addressing muscle-tendon imbalances in adult male athletes with personalized exercise prescription based on tendon strain.

PURPOSE: Imbalances of muscle strength and tendon stiffness can increase the operating strain of tendons and risk of injury. Here, we used a new approach to identify muscle-tendon imbalances and personalize exercise prescription based on tendon strain during maximum voluntary contractions (εmax) to mitigate musculotendinous imbalances in male adult volleyball athletes. METHODS: Four times over a season, we measured knee extensor strength and patellar tendon mechanical properties using dynamometry and ultrasonography. Tendon micromorphology was evaluated through an ultrasound peak spatial frequency (PSF) analysis. While a control group (n = 12) continued their regular training, an intervention group (n = 10) performed exercises (3 × /week) with personalized loads to elicit tendon strains that promote tendon adaptation (i.e., 4.5-6.5%). RESULTS: Based on a linear mixed model, εmax increased significantly in the control group over the 9 months of observation (pCon = 0.010), while there was no systematic change in the intervention group (pInt = 0.575). The model residuals of εmax, as a measure of imbalances in muscle-tendon adaptation, demonstrated a significant reduction over time exclusively in the intervention group (pInt = 0.007). While knee extensor muscle strength increased in both groups by ~ 8% (pCon < 0.001, pInt = 0.064), only the intervention group showed a trend toward increased normalized tendon stiffness (pCon = 0.824, pInt = 0.051). PSF values did not change significantly in either group (p > 0.05). CONCLUSION: These results suggest that personalized exercise prescription can reduce muscle-tendon imbalances in athletes and could provide new opportunities for tendon injury prevention.

Speed-specific optimal contractile conditions of the human soleus muscle from slow to maximum running speed.

The soleus is the main muscle for propulsion during human running but its operating behavior across the spectrum of physiological running speeds is currently unknown. This study experimentally investigated the soleus muscle activation patterns and contractile conditions for force generation, power production and efficient work production (i.e. force-length potential, force-velocity potential, power-velocity potential and enthalpy efficiency) at seven running speeds (3.0 m s-1 to individual maximum). During submaximal running (3.0-6.0 m s-1), the soleus fascicles shortened close to optimal length and at a velocity close to the efficiency maximum, two contractile conditions for economical work production. At higher running speeds (7.0 m s-1 to maximum), the soleus muscle fascicles still operated near optimum length, yet the fascicle shortening velocity increased and shifted towards the optimum for mechanical power production with a simultaneous increase in muscle activation, providing evidence for three cumulative mechanisms to enhance mechanical power production. Using the experimentally determined force-length-velocity potentials and muscle activation as inputs in a Hill-type muscle model, a reduction in maximum soleus muscle force at speeds ≥7.0 m s-1 and a continuous increase in maximum mechanical power with speed were predicted. The reduction in soleus maximum force was associated with a reduced force-velocity potential. The increase in maximum power was explained by an enhancement of muscle activation and contractile conditions until 7.0 m s-1, but mainly by increased muscle activation at high to maximal running speed.

Effect of sex on muscle-tendon imbalances and tendon micromorphology in adolescent athletes-A longitudinal consideration.

Imbalances between muscle strength and tendon stiffness may cause high-level tendon strain during maximum effort muscle contractions and lead to tendon structural impairments and an increased risk for tendinopathy in adolescent athletes. However, it remains unclear whether the development of musculotendinous imbalances is influenced by sex. At four measurement time points during a competitive season, we measured quadriceps femoris muscle strength and patellar tendon mechanical properties in 15 female (14.3 ± 0.7 years) and 13 male (16.0 ± 0.6 years) elite handball players of similar maturity using dynamometry and ultrasonography. To estimate the tendon's structural integrity, the peak spatial frequency (PSF) of proximal tendon ultrasound scans was determined. Females demonstrated significantly lower muscle strength (p < 0.001) and patellar tendon stiffness (p < 0.001) than males with no significant changes over time (p > 0.05). Tendon strain during isometric maximum voluntary contractions and PSF neither differed between sexes nor changed significantly over time (p > 0.05). We found lower fluctuations in muscle strength (p < 0.001) in females during the season but no differences in the fluctuations of tendon strain, stiffness, and PSF (p > 0.05). Descriptively, there was a similar frequency (~40%) of athletes with high-level tendon strain (>9%) in both sexes. These findings suggest that the lower strength capacity of female athletes is paralleled by lower tendon stiffness. Thereby, muscle-tendon imbalances occur to a similar extent in both sexes leading to increased strain levels during the season, which indicates the need for specific tendon training.

Pneumothorax detection with thoracic ultrasound as the method of choice in interventional pulmonology - A retrospective single-center analysis and experience.

BACKGROUND: Recent studies have shown that thoracic ultrasound (TUS) is not inferior to chest radiography (CR) in detecting pneumothorax (PTX). It is unclear if adopting TUS can reduce the number of CR in the daily clinical routine. This retrospective study investigates the utilization of post-interventional CR and TUS for PTX detection after the introduction of TUS as the method of choice in an interventional pulmonology unit. METHODS: All interventions with CR or TUS for ruling out PTX performed in the Pneumology Department of the University Hospital Halle (Germany) 2014 to 2020 were included. The documented TUS and CR performed before (period A) and after the introduction of TUS as the method of choice (period B), as well as the number of diagnosed and missed PTX were recorded. RESULTS: The study included 754 interventions (110 in period A and 644 in period B). The proportion of CR decreased from 98.2% (n = 108) to 25.8% (n = 166) (p < 0.001). During period B, a total of 29 (4.5%) PTX were diagnosed. Of these, 28 (96.6%) were detected on initial imaging (14 by CR, 14 by TUS ). One PTX (0.2%) was initially missed by TUS, none by CR. Confirmatory investigations were ordered more frequently after TUS (21 of 478, 4.4%) than after CR (3 of 166, 1.8%). CONCLUSION: The use of TUS in interventional pulmonology can effectively reduce the number of CR and thus save resources. However, CR may still be favored in specific circumstances or if pre-existing conditions limit sonographic findings.

Inflammatory Bowel Disease and COVID-19: How Have Patients Coped So Far?

OBJECTIVE: Knowledge about SARS-CoV2 and coronavirus disease 2019 (COVID-19) is growing fast. Massive changes in the health care system imposed by the COVID-19 pandemic clearly impact the overall quality of medical care. In this survey, we aim to explore experiences and concerns of patients with inflammatory bowel disease (IBD) regarding the current pandemic. METHODS: A 40-item web-based questionnaire on disease-related experiences and concerns during the COVID-19 pandemic was made available to patients with IBD from 28 April 2020 to 31 July 2020. RESULTS: An increased risk of SARS-CoV2 infection was a concern for 56.7% of the 1199 patients (aged 41.3±12.8, women 77%, Crohn's disease 58.8%, ulcerative colitis 38.5%); 61.7% feared an increased risk of severe disease course of COVID-19. Effective preventive measures in either outpatient practices or hospitals were observed by 84.7% of the patients. Appointments with an IBD specialist were canceled in 38.7%, frequently on the patients' initiative. Telecommunication visits were considered an acceptable alternative to personal visits by 71.0%. Medication was reduced or paused in 6.9% because of the pandemic. A swab (SARS-CoV2-PCR) was done in 13.2% of the patients; only 3 patients (0.25%) were tested positive. CONCLUSION: The COVID-19 pandemic is a major concern of patients with IBD. However, the cumulative prevalence in our cohort is low. Patients at risk should be identified and counseled individually. When required because of the local COVID-19 situation, telecommunication visits and liberal prescription policies are advisable to reduce in-person contacts, while ensuring continuous therapy and maintaining communication with patients.

Enthalpy efficiency of the soleus muscle contributes to improvements in running economy.

During human running, the soleus, as the main plantar flexor muscle, generates the majority of the mechanical work through active shortening. The fraction of chemical energy that is converted into muscular work (enthalpy efficiency) depends on the muscle shortening velocity. Here, we investigated the soleus muscle fascicle behaviour during running with respect to the enthalpy efficiency as a mechanism that could contribute to improvements in running economy after exercise-induced increases of plantar flexor strength and Achilles tendon (AT) stiffness. Using a controlled longitudinal study design (n = 23) featuring a specific 14-week muscle-tendon training, increases in muscle strength (10%) and tendon stiffness (31%) and reduced metabolic cost of running (4%) were found only in the intervention group (n = 13, p < 0.05). Following training, the soleus fascicles operated at higher enthalpy efficiency during the phase of muscle-tendon unit (MTU) lengthening (15%) and in average over stance (7%, p < 0.05). Thus, improvements in energetic cost following increases in plantar flexor strength and AT stiffness seem attributed to increased enthalpy efficiency of the operating soleus muscle. The results further imply that the soleus energy production in the first part of stance, when the MTU is lengthening, may be crucial for the overall metabolic energy cost of running.

Prevention of strain-induced impairments of patellar tendon micromorphology in adolescent athletes.

High-level patellar tendon strain may cause impairments of the tendon's micromorphological integrity in growing athletes and increase the risk for tendinopathy. This study investigated if an evidence-based tendon exercise intervention prevents high-level patellar tendon strain, impairments of micromorphology and pain in adolescent basketball players (male, 13-15 years). At three time points over a season (M1-3), tendon mechanical properties were measured using ultrasound and dynamometry, proximal tendon micromorphology with a spatial frequency analysis and pain and disability using VISA-P scores. The control group (CON, n = 19) followed the usual strength training plan, including sprint and change-of-direction drills. In the intervention group (INT, n = 14), three sessions per week with functional exercises were integrated into the training, providing repetitive high-magnitude tendon loading for at least 3 s per repetition. The frequency of high-level strain (ie, ≥9%) continuously decreased in INT, while tending to increase in CON since tendon force increased in both (p < 0.001), yet tendon stiffness only in INT (p = 0.004). In CON, tendon strain was inversely associated with tendon peak spatial frequency at all time points (p < 0.05), indicating impairments of tendon micromorphological integrity with higher strain, but not at M2 and M3 in INT. Descriptively, the fraction of asymptomatic athletes at baseline was similar in both groups (~70%) and increased to 100% in M3 in INT, while remaining unchanged in CON. We suggest that functional high-load tendon exercises could reduce the prevalence of high-level patellar tendon strain and associated impairments of its micromorphology in adolescent athletes, providing new opportunities for tendinopathy prevention.

Reliable and effective novel home-based training set-up for application of an evidence-based high-loading stimulus to improve triceps surae function.

High-loading interventions aiming for muscle-tendon adaptations were so far implemented in on-site facilities. To make this evidence-based stimulus more accessible, we developed an easy-to-use sling-based training set-up for home-based Achilles tendon and triceps surae muscle strength training and assessed its reliability and effectiveness in healthy men. To assess reliability (n=11), intra-class correlation (ICC) and root mean square (RMS) differences of isometric maximum voluntary contraction (MVC) of the plantar flexors were used. Effectiveness was tested in a controlled intervention trial (n=12), applying one-legged high-loading intervention for 3 months with our mobile set-up, while the contralateral/untrained leg served as control, and assessing plantar flexor MVC, drop (DJ) and countermovement jump (CMJ) height. Reliability was excellent between (ICCB=0.935) and within session (ICCWs=0.940-0.967). The mean RMS difference between and within sessions was 5.3% and 4.7%, respectively. MVCs of the trained/intervention leg increased by 10.2±7% (P=0.004) (dynamometry) and 30.2±22.5% (mobile set-up) (P=0.012). MVC of the untrained/control leg did not change (P>0.05). DJ height increased (P=0.025; Dz=2.13) by 2.37±2.9cm. CMJ height (P>0.05) did not change. We recommend the evidence-based high-loading application with our novel home-based training set-up as reliable and effective improving strength and jump performance of the plantar flexor muscle-tendon unit.

A Simplified Method for Considering Achilles Tendon Curvature in the Assessment of Tendon Elongation.

The consideration of the Achilles tendon (AT) curvature is crucial for the precise determination of AT length and strain. We previously established an ultrasound-kinematic-based method to quantify the curvature, using a line of reflective foil skin markers covering the AT from origin to insertion. The current study aimed to simplify the method by reducing the number of markers while maintaining high accuracy. Eleven participants walked (1.4 m/s) and ran (2.5, 3.5 m/s) on a treadmill, and the AT curvature was quantified using reflective foil markers aligned with the AT between the origin on the gastrocnemius myotendinous-junction (tracked by ultrasound) and a marker on the calcaneal insertion. Foil markers were then systematically removed, and the introduced error on the assessment of AT length and strain was calculated. We found a significant main effect of marker number on the measurement error of AT length and strain (p<0.001). Using more than 30% of the full marker-set for walking and 50% for running, the R2 of the AT length error saturated, corresponding to average errors of <0.1 mm and <0.15% strain. Therefore, a substantially reduced marker-set, associated with a marginal error, can be recommended for considering the AT curvature in the determination of AT length and strain.

Effects of long-term athletic training on muscle morphology and tendon stiffness in preadolescence: association with jump performance.

PURPOSE: Evidence on training-induced muscle hypertrophy during preadolescence is limited and inconsistent. Possible associations of muscle strength and tendon stiffness with jumping performance are also not investigated. We investigated the thickness and pennation angle of the gastrocnemius medialis muscle (GM), as indicators for potential muscle hypertrophy in preadolescent athletes. Further, we examined the association of triceps surae muscle-tendon properties with jumping performance. METHODS: Eleven untrained children (9 years) and 21 similar-aged artistic gymnastic athletes participated in the study. Muscle thickness and pennation angle of the GM were measured at rest and muscle strength of the plantar flexors and Achilles tendon stiffness during maximum isometric contractions. Jumping height in squat (SJ) and countermovement jumps (CMJ) was examined using a force plate. We evaluated the influence of normalised muscle strength and tendon stiffness on jumping performance with a linear regression model. RESULTS: Muscle thickness and pennation angle did not differ significantly between athletes and non-athletes. In athletes, muscle strength was greater by 25% and jumping heights by 36% (SJ) and 43% (CMJ), but Achilles tendon stiffness did not differ between the two groups. The significant predictor for both jump heights was tendon stiffness in athletes and normalised muscle strength for the CMJ height in non-athletes. CONCLUSION: Long-term artistic gymnastics training during preadolescence seems to be associated with increased muscle strength and jumping performance but not with training-induced muscle hypertrophy or altered tendon stiffness in the plantar flexors. Athletes benefit more from tendon stiffness and non-athletes more from muscle strength for increased jumping performance.

The force-length-velocity potential of the human soleus muscle is related to the energetic cost of running.

According to the force-length-velocity relationships, the muscle force potential is determined by the operating length and velocity, which affects the energetic cost of contraction. During running, the human soleus muscle produces mechanical work through active shortening and provides the majority of propulsion. The trade-off between work production and alterations of the force-length and force-velocity potentials (i.e. fraction of maximum force according to the force-length-velocity curves) might mediate the energetic cost of running. By mapping the operating length and velocity of the soleus fascicles onto the experimentally assessed force-length and force-velocity curves, we investigated the association between the energetic cost and the force-length-velocity potentials during running. The fascicles operated close to optimal length (0.90 ± 0.10 L0) with moderate velocity (0.118 ± 0.039 Vmax [maximum shortening velocity]) and, thus, with a force-length potential of 0.92 ± 0.07 and a force-velocity potential of 0.63 ± 0.09. The overall force-length-velocity potential was inversely related (r = -0.52, p = 0.02) to the energetic cost, mainly determined by a reduced shortening velocity. Lower shortening velocity was largely explained (p < 0.001, R2 = 0.928) by greater tendon gearing, shorter Achilles tendon lever arm, greater muscle belly gearing and smaller ankle angle velocity. Here, we provide the first experimental evidence that lower shortening velocities of the soleus muscle improve running economy.

Grating assisted glass fiber coupler for mode selective co-directional coupling.

To keep pace with the increasing demand of transmission capacity, space division multiplexing technologies are currently intensively investigated. In this context, mode selective glass fiber couplers are of great interest due to their compatibility with existing glass fiber networks. In this work, we present a novel type of mode selective glass fiber coupler for co-directional coupling based on fiber gratings and fused asymmetric fibers. The achieved mode selective coupling efficiency agrees well with numerical simulations performed for comparison. The benefits of the grating approach are a lower mode crosstalk and a simple adaption of the propagation constants through changing of the grating-period.

Reliability of a semi-automated algorithm for the vastus lateralis muscle architecture measurement based on ultrasound images.

PURPOSE: The assessment of muscle architecture with B-mode ultrasound is an established method in muscle physiology and mechanics. There are several manual, semi-automated and automated approaches available for muscle architecture analysis from ultrasound images or videos. However, most approaches have limitations such as workload, subjectivity, drift or they are applicable to short muscle fascicles only. Addressing these issues, an algorithm was developed to analyse architectural parameters of the vastus lateralis muscle (VL). METHODS: In 17 healthy young men and women, ultrasound images were taken five times on two different days during passive knee joint flexion. From the images, fascicle length (FL), pennation angle (PAN) and muscle thickness (MTH) were calculated for both test days using the algorithm. Interday differences were determined using a two-way ANOVA. Interday and intraday reliability were assessed using intraclass correlation coefficients (ICC) and root mean square (RMS) differences. RESULTS: FL, MTH and PAN did not differ between day one and two. The within day ICCs were above 0.94 for all tested parameters. The average interday ICCs were 0.86 for the FL, 0.96 for MTH and 0.60 for PAN. The average RMS differences between both days were 5.0%, 8.5% and 12.0% for MTH, FL and PAN, respectively. CONCLUSION: The proposed algorithm provides high measurement reliability. However, the interday reliability might be influenced by small differences in probe position between days.

Long-Period Gratings in Highly Germanium-Doped, Single-Mode Optical Fibers for Sensing Applications.

Long-period fiber gratings (LPGs) are well known for their sensitivity to external influences, which make them interesting for a large number of sensing applications. For these applications, fibers with a high numerical aperture (i.e., fibers with highly germanium (Ge)-doped fused silica fiber cores) are more attractive since they are intrinsically photosensitive, as well as less sensitive to bend- and microbend-induced light attenuations. In this work, we introduce a novel method to inscribe LPGs into highly Ge-doped, single-mode fibers. By tapering the optical fiber, and thus, tailoring the effective indices of the core and cladding modes, for the first time, an LPG was inscribed into such fibers using the amplitude mask technique and a KrF excimer laser. Based on this novel method, sensitive LPG-based fiber optic sensors only a few millimeters in length can be incorporated in bend-insensitive fibers for use in various monitoring applications. Moreover, by applying the described inscription method, the LPG spectrum can be influenced and tailored according to the specific demands of a particular application.

Functional Characterization of Glycoprotein H Chimeras Composed of Conserved Domains of the Pseudorabies Virus and Herpes Simplex Virus 1 Homologs.

UNLABELLED: Membrane fusion is indispensable for entry of enveloped viruses into host cells. The conserved core fusion machinery of the Herpesviridae consists of glycoprotein B (gB) and the gH/gL complex. Recently, crystal structures of gH/gL of herpes simplex virus 2 (HSV-2) and Epstein-Barr virus and of a core fragment of pseudorabies virus (PrV) gH identified four structurally conserved gH domains. To investigate functional conservation, chimeric genes encoding combinations of individual domains of PrV and herpes simplex virus 1 (HSV-1) gH were expressed in rabbit kidney cells, and their processing and transport to the cell surface, as well as activity in fusion assays including gB, gD, and gL of PrV or HSV-1, were analyzed. Chimeric gH containing domain I of HSV-1 and domains II to IV of PrV exhibited limited fusion activity in the presence of PrV gB and gD and HSV-1 gL, but not of PrV gL. More strikingly, chimeric gH consisting of PrV domains I to III and HSV-1 domain IV exhibited considerable fusion activity together with PrV gB, gD, and gL. Replacing PrV gB with the HSV-1 protein significantly enhanced this activity. A cell line stably expressing this chimeric gH supported replication of gH-deleted PrV. Our results confirm the specificity of domain I for gL binding, demonstrate functional conservation of domain IV in two alphaherpesviruses from different genera, and indicate species-specific interactions of this domain with gB. They also suggest that gH domains II and III might form a structural and functional unit which does not tolerate major substitutions. IMPORTANCE: Envelope glycoprotein H (gH) is essential for herpesvirus-induced membrane fusion, which is required for host cell entry and viral spread. Although gH is structurally conserved within the Herpesviridae, its precise role and its interactions with other components of the viral fusion machinery are not fully understood. Chimeric proteins containing domains of gH proteins from different herpesviruses can serve as tools to elucidate the molecular basis of gH function. The present study shows that the C-terminal part of human herpesvirus 1 (herpes simplex virus 1) gH can functionally substitute for the corresponding part of suid herpesvirus 1 (pseudorabies virus) gH, whereas other tested combinations proved to be nonfunctional. Interestingly, the exchangeable fragment included the membrane-proximal end of the gH ectodomain (domain IV), which is most conserved in sequence and structure and might be capable of transient membrane interaction during fusion.