Deletion of MGF505-2R Gene Activates the cGAS-STING Pathway Leading to Attenuation and Protection against Virulent African Swine Fever Virus.

African swine fever virus (ASFV) is the etiological agent causing African swine fever (ASF), affecting domestic pigs and wild boar, which is currently the biggest animal epidemic in the world and a major threat to the swine sector. At present, some safety concerns about using LAVs against ASFV still exist despite a commercial vaccine licensed in Vietnam. Therefore, the efforts to identify virulence factors and their mechanisms, as well as to generate new vaccine prototypes, are of major interest. In this work, we have identified the MGF505-2R gene product as an inhibitor of the cGAS/STING pathway, specifically through its interaction with STING protein, controlling IFN-ß production. In addition, immunization of a recombinant virus lacking this gene, Arm/07-ΔMGF505-2R, resulted in complete attenuation, demonstrating its involvement in ASFV virulence. Finally, immunization with Arm/07-ΔMGF505-2R induced the generation of antibodies and proved to be partially protective against virulent ASFV strains. These results identify MGF505-2R, as well as its mechanism of action, as a gene contributing to understanding the molecular mechanisms of ASFV virulence, which will be of great value in the design of future vaccine prototypes.

Genome characterization of a Korean isolate of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED) outbreaks occur annually in the Republic of Korea. The complete genome sequence of the PED virus isolate CKK1-1 obtained from an infected pig was determined. The genome is 28,037 nt long, excluding the poly(A) tail, and contains seven open reading frames flanked by two untranslated regions.

Alteration of the Gut Microbiota in Pigs Infected with African Swine Fever Virus.

The factors that influence the pathogenicity of African swine fever (ASF) are still poorly understood, and the host's immune response has been indicated as crucial. Although an increasing number of studies have shown that gut microbiota can control the progression of diseases caused by viral infections, it has not been characterized how the ASF virus (ASFV) changes a pig's gut microbiome. This study analyzed the dynamic changes in the intestinal microbiome of pigs experimentally infected with the high-virulence ASFV genotype II strain (N = 4) or mock strain (N = 3). Daily fecal samples were collected from the pigs and distributed into the four phases (before infection, primary phase, clinical phase, and terminal phase) of ASF based on the individual clinical features of the pigs. The total DNA was extracted and the V4 region of the 16 s rRNA gene was amplified and sequenced on the Illumina platform. Richness indices (ACE and Chao1) were significantly decreased in the terminal phase of ASF infection. The relative abundances of short-chain-fatty-acids-producing bacteria, such as Ruminococcaceae, Roseburia, and Blautia, were decreased during ASFV infection. On the other hand, the abundance of Proteobacteria and Spirochaetes increased. Furthermore, predicted functional analysis using PICRUSt resulted in a significantly reduced abundance of 15 immune-related pathways in the ASFV-infected pigs. This study provides evidence for further understanding the ASFV-pig interaction and suggests that changes in gut microbiome composition during ASFV infection may be associated with the status of immunosuppression.

Development of Effective PEDV Vaccine Candidates Based on Viral Culture and Protease Activity.

Porcine epidemic diarrhea (PED) is a highly contagious disease that has been reported annually in several Asian countries, causing significant economic losses to the swine livestock industry. Although vaccines against the porcine epidemic diarrhea virus (PEDV) are available, their efficacy remains questionable due to limitations such as viral genome mutation and insufficient intestinal mucosal immunity. Therefore, the development of a safe and effective vaccine is necessary. In this study, a virulent Korean strain of PEDV, CKT-7, was isolated from a piglet with severe diarrhea, and six different conditions were employed for serial passage of the strain in a cell culture system to generate effective live attenuated vaccine (LAV) candidates. The characteristics of these strains were analyzed in vitro and in vivo, and the CKT-7 N strain was identified as the most effective vaccine candidate, with a viral titer peak of 8.67 ± 0.29 log10TCID50/mL, and no mortality or diarrhea symptoms were observed in five-day-old piglets. These results indicate that LAV candidates can be generated through serial passage with different culture conditions and provide valuable insights into the development of a highly effective LAV against PEDV.

Delta (B1.617.2) variant of SARS-CoV-2 induces severe neurotropic patterns in K18-hACE2 mice.

A highly contagious virus, severe acute respiratory syndrome coronavirus 2, caused the coronavirus disease 19 (COVID-19) pandemic (SARS-CoV-2). SARS-CoV-2 genetic variants have been reported to circulate throughout the COVID-19 pandemic. COVID-19 symptoms include respiratory symptoms, fever, muscle pain, and breathing difficulty. In addition, up to 30% of COVID-19 patients experience neurological complications such as headaches, nausea, stroke, and anosmia. However, the neurotropism of SARS-CoV-2 infection remains largely unknown. This study investigated the neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan, early strain) in K18-hACE2 mice. Despite both the variants inducing similar pathogenic patterns in various organs, B1.617.2-infected K18-hACE2 mice demonstrated a higher range of disease phenotypes such as weight loss, lethality, and conjunctivitis when compared to those in Hu-1-infected mice. In addition, histopathological analysis revealed that B1.617.2 infects the brain of K18-hACE2 mice more rapidly and effectively than Hu-1. Finally, we discovered that, in B1.617.2-infected mice, the early activation of various signature genes involved innate cytokines and that the necrosis-related response was most pronounced than that in Hu-1-infected mice. The present findings indicate the neuroinvasive properties of SARS-CoV-2 variants in K18-hACE2 mice and link them to fatal neuro-dissemination during the disease onset.

Recombinant African Swine Fever Virus Arm/07/CBM/c2 Lacking CD2v and A238L Is Attenuated and Protects Pigs against Virulent Korean Paju Strain.

African swine fever (ASF) is an obligated declaration swine disease, provoking farm isolation measures and the closing of affected country boarders. ASF virus (ASFV) is currently the cause of a pandemic across China and Eurasia. By the end of 2019, ASF was detected in nine EU Member States: Bulgaria, Romania, Slovakia, Estonia, Hungary, Latvia, Lithuania, Poland and Belgium. The affected area of the EU extended progressively, moving mostly in a southwestern direction (EFSA). Inactivated and/or subunit vaccines have proven to fail since certain virus replication is needed for protection. LAVs are thus the most realistic option, which must be safe, effective and industrially scalable. We here generated a vaccine prototype from the Arm/07/CBM/c2 genotype II strain, in which we have deleted the EP402R (CD2v) and A238L genes by CRISPR/Cas9 in COS-1 cells, without detectable further genetic changes. The successful immunization of pigs has proven this vaccine to be safe and fully protective against the circulating Korean Paju genotype II strain, opening the possibility of a new vaccine on the market in the near future.

Application of AULA Risk Assessment Tool by Comparison with Other Ergonomic Risk Assessment Tools.

Agricultural upper limb assessment (AULA), which was developed for evaluating upper limb body postures, was compared with the existing assessment tools such as rapid upper limb assessment (RULA), rapid entire body assessment (REBA), and ovako working posture analysis system (OWAS) based on the results of experts' assessments of 196 farm tasks in this study. The expert group consisted of ergonomists, industrial medicine experts, and agricultural experts. As a result of the hit rate analysis, the hit rate (average: 48.6%) of AULA was significantly higher than those of the other assessment tools (RULA: 33.3%, REBA: 30.1%, and OWAS: 34.4%). The quadratic weighted kappa analysis also showed that the kappa value (0.718) of AULA was significantly higher than those of the other assessment tools (0.599, 0.578, and 0.538 for RULA, REBA, and OWAS, respectively). Based on the results, AULA showed a better agreement with expert evaluation results than other evaluation tools. In general, other assessment tools tended to underestimate the risk of upper limb posture in this study. AULA would be an appropriate evaluation tool to assess the risk of various upper limb postures.

Evaluation of the controlled grip force exertion tasks associated with age, gender, handedness and target force level.

INTRODUCTION: Force control of the hand is an essential factor for operating tools and moving objects. Therefore, a method for quantifying hand functionality more accurately and objectively is very important. METHODS: The present study included 60 healthy participants (30 elderly and 30 young adults) to evaluate the effects of age, gender and target force levels on tracking performance. Tracking performance was quantified by measuring the difference between target force levels and exerted force. RESULTS: Females exerted 59.6% of the maximum grip strength of males and the elderly group exerted 70.5% of maximum grip strength compared with the young group. The elderly group showed 3.1 times larger tracking error than the young group. There was a significant difference in females between the young and elderly groups, indicating age-related decline in hand function is more pronounced in females. The difference in grip force control ability between the elderly and young groups was significant at the low target force level (5% maximum voluntary contraction). CONCLUSIONS: The results of this study could be used for hand function evaluation guidelines. In addition, this study could be used as a tool for physiotherapy to improve hand function and prevent its decline in elderly people.

Comparisons of ergonomic evaluation tools (ALLA, RULA, REBA and OWAS) for farm work.

INTRODUCTION: The purpose of this study was to validate the agricultural lower limb assessment (ALLA) ergonomic checklist, which was developed for various agricultural tasks in Korea. METHODS: One hundred and ninety-six working postures were selected from the real agricultural tasks to verify ALLA, a lower limb body posture assessment tool, and then evaluated by 16 ergonomic experts. Hit rate, quadratic weighted κ, one-way analysis of variance and t-test analyses were applied to compare ALLA with other assessment tools. RESULTS: ALLA analysis had a superior hit rate with ergonomic expert assessment compared with other assessment tools. Quadratic weighted κ analysis also showed that ALLA provided superior estimates of risk levels for farm working postures. DISCUSSION: ALLA would be an appropriate assessment tool to estimate risk factors for various lower limb body postures which frequently occur in agricultural tasks in Korea. ALLA is a simple and accurate risk assessment tool that could be usefully applied to identify and mitigate risk factors and work-related musculoskeletal disorders in agricultural tasks, and also to evaluate the effects of control and intervention for working conditions.

Investigation of index finger triggering force using a cadaver experiment: Effects of trigger grip span, contact location, and internal tendon force.

A cadaver study was conducted to investigate the effects of triggering conditions (trigger grip span, contact location, and internal tendon force) on index finger triggering force and the force efficiency of involved tendons. Eight right human cadaveric hands were employed, and a motion simulator was built to secure and control the specimens. Index finger triggering forces were investigated as a function of different internal tendon forces (flexor digitorum profundus + flexor digitorum superficialis = 40, 70, and 100 N), trigger grip spans (40, 50, and 60 mm), and contact locations between the index finger and a trigger. Triggering forces significantly increased when internal tendon forces increased from 40 to 100 N. Also, trigger grip spans and contact locations had significant effects on triggering forces; maximum triggering forces were found at a 50 mm span and the most proximal contact location. The results revealed that only 10-30% of internal tendon forces were converted to their external triggering forces.

Investigation of methods for estimating hand bone dimensions using X-ray hand anthropometric data.

This study examined two conversion methods, M1 and M2, to predict finger/phalange bone lengths based on finger/phalange surface lengths. Forty-one Korean college students (25 males and 16 females) were recruited and their finger/phalange surface lengths, bone lengths and grip strengths were measured using a vernier caliper, an X-ray generator and a double-handle force measurement system, respectively. M1 and M2 were defined as formulas able to estimate finger/phalange bone lengths based on one dimension (i.e., surface hand length) and four finger dimensions (surface finger lengths), respectively. As a result of conversion, the estimation errors by M1 presented mean 1.22 mm, which was smaller than those (1.29 mm) by M2. The bone lengths estimated by M1 (mean r = 0.81) presented higher correlations with the measured bone lengths than those estimated by M2 (0.79). Thus, the M1 method was recommended in the present study, based on conversion simplicity and accuracy.

Evaluation of pliers' grip spans in the maximum gripping task and sub-maximum cutting task.

A total of 25 males participated to investigate the effects of the grip spans of pliers on the total grip force, individual finger forces and muscle activities in the maximum gripping task and wire-cutting tasks. In the maximum gripping task, results showed that the 50-mm grip span had significantly higher total grip strength than the other grip spans. In the cutting task, the 50-mm grip span also showed significantly higher grip strength than the 65-mm and 80-mm grip spans, whereas the muscle activities showed a higher value at 80-mm grip span. The ratios of cutting force to maximum grip strength were also investigated. Ratios of 30.3%, 31.3% and 41.3% were obtained by grip spans of 50-mm, 65-mm, and 80-mm, respectively. Thus, the 50-mm grip span for pliers might be recommended to provide maximum exertion in gripping tasks, as well as lower maximum-cutting force ratios in the cutting tasks.

The relationship between hand anthropometrics, total grip strength and individual finger force for various handle shapes.

The design and shape of hand tool handles are critical factors for preventing musculoskeletal disorders (MSDs) caused by the use of hand tools. We explored how these factors are related to total force and individual finger force in males and females with various hand anthropometrics. Using the MFFM system, we assessed four indices of anthropometry, and measured total force and individual finger force on various handle designs and shapes. Both total force and individual finger force were significant according to gender and handle shape. Total grip strength to the handle shape indicated the greatest strength with D shape and the least with A shape. From the regression analysis of hand anthropometric indices, the value of R was respectably high at 0.608-0.696. The current study examined the gender and handle shape factors affecting grip strength based on the force measurements from various handle types, in terms of influence on different hand anthropometric indices.

Effect of finger interaction on individual finger: index finger.

Grip strength is affected by such as enslaving effect, force sharing effect, and force deficit effect relating to the interaction among fingers. The author attempts to analyze index finger strength according to grip span of adjacent middle finger. 6 male graduate students participated as subjects in this experiment. The grip span has been applied from 45 mm to 60mm to investigate the effects of a coordination of grip spans on the index and middle finger strength. Results showed that index finger strength was the smallest in case of index finger grip span of 45 mm. Index finger strength decreased as the middle finger grip span. In general index finger strength shared a decreasing trend when the grip span of the middle finger increased. This study has an implication that the grip span of index and middle fingers influences force sharing effect on index finger.

Comparison of comfort, discomfort, and continuum ratings of force levels and hand regions during gripping exertions.

The goal of this study was to compare three different evaluation systems of comfort, discomfort, and a continuum for the force levels and hand regions when gripping hand tools. Seventy-two participants were assigned to three groups, each group testing a different evaluation system. Each participant exerted ten levels of submaximal voluntary contractions on hand tools and used their assigned evaluation system to evaluate comfortable or uncomfortable feelings for the force levels and five different regions of the hand. The participants generally rated higher discomfort as required forces increased, but the discomfort and continuum evaluation systems were better than the comfort evaluation system because gripping exertion was related to the physical aspects of the hand tools and their users. Based on the results of the continuum evaluation system, the feeling changed from comfort to discomfort at 65% maximum voluntary contraction. The palm was the region of the hand with the most discomfort. Other design factors affecting comfort need to also be considered in order to better understand hand tool use.

Individual finger contribution in submaximal voluntary contraction of gripping.

The objective of this study was to evaluate individual finger force and contribution to a gripping force, the difference between actual and expected finger forces and subjective discomfort rating at 10 different submaximal voluntary contraction (%MVC) levels (10-100% in 10 increments). Seventy-two participants randomly exerted gripping force with a multi-finger force measurement system. The individual finger force, gripping force and discomfort increased as %MVC levels increased. The middle and ring fingers exerted more force and contributed to a gripping force more than the index and little fingers due to their larger mass fractions of the digit flexor muscles. It was apparent at <50% MVC; however, the index finger increased its contribution and exerted even more force than expected at more than 50% MVC. Subjective discomfort supported the results of the objective measures. This could explain the conflicting findings between index and ring fingers in previous finger contribution studies. STATEMENT OF RELEVANCE: Hand tool design is of special interest in ergonomics due to its association with musculoskeletal disorders in the hand. This study reveals a different contribution pattern of the fingers in submaximal voluntary contraction of gripping exertion.

The effects of knee angles on subjective discomfort ratings, heart rates, and muscle fatigue of lower extremities in static-sustaining tasks.

The purpose of this study was to investigate the effects of knee-flexion angles on subjective discomfort ratings, heart rates, and muscle fatigue using median frequency (MDF) in a static-sustaining task. Thirty healthy participants maintained 13 postures including standing, squatting, sitting, and kneeling postures and then MDFs from the erector spinae, biceps femoris, vastus medialis, gastrocnemius, and tibialis anterior muscles, subjective discomfort, and heart rates were collected every 3 min during a sustained 15 min task. Results showed that the discomfort, heart rate and muscle fatigue were significantly influenced by the body postures. In general, standing and sitting postures showed less discomfort as well as lower heart rates, whereas squatting postures (KF120, KF90, KF60) had higher discomfort and heart rates. Three MDF change trends were reported associated with postures in this study. First, there were less changes of MDFs for standing and sitting postures; second, all patterns of MDFs for KF 150 and KF120 decreased, and lastly some MDFs had increasing trends and others showed decreasing trends for KF30, KF30T, and kneeling postures.