Deltex family E3 ligases specifically ubiquitinate the terminal ADP-ribose of poly(ADP-ribosyl)ation.

Poly(ADP-ribose) polymerases (PARPs) are critical to regulating cellular activities, such as the response to DNA damage and cell death. PARPs catalyze a reversible post-translational modification (PTM) in the form of mono- or poly(ADP-ribosyl)ation. This type of modification is known to form a ubiquitin-ADP-ribose (Ub-ADPR) conjugate that depends on the actions of Deltex family of E3 ubiquitin ligases (DTXs). In particular, DTXs add ubiquitin to the 3'-OH of adenosine ribose' in ADP-ribose, which effectively sequesters ubiquitin and impedes ubiquitin-dependent signaling. Previous work demonstrates DTX function for ubiquitination of protein-free ADPR, mono-ADP-ribosylated peptides, and ADP-ribosylated nucleic acids. However, the dynamics of DTX-mediated ubiquitination of poly(ADP-ribosyl)ation remains to be defined. Here we show that the ADPR ubiquitination function is not found in other PAR-binding E3 ligases and is conserved across DTX family members. Importantly, DTXs specifically target poly(ADP-ribose) chains for ubiquitination that can be cleaved by PARG, the primary eraser of poly(ADP-ribose), leaving the adenosine-terminal ADPR unit conjugated to ubiquitin. Our collective results demonstrate the DTXs' specific ubiquitination of the adenosine terminus of poly(ADP-ribosyl)ation and suggest the unique Ub-ADPR conjugation process as a basis for PARP-DTX control of cellular activities.

F-RDW: Redirected Walking With Forecasting Future Position.

In order to serve better VR experiences to users, existing predictive methods of Redirected Walking (RDW) exploit future information to reduce the number of reset occurrences. However, such methods often impose a precondition during deployment, either in the virtual environment's layout or the user's walking direction, which constrains its universal applications. To tackle this challenge, we propose a mechanism F-RDW that is twofold: (1) forecasts the future information of a user in the virtual space without any assumptions by using the conventional method, and (2) fuse this information while maneuvering existing RDW methods. The backbone of the first step is an LSTM-based model that ingests the user's spatial and eye-tracking data to predict the user's future position in the virtual space, and the following step feeds those predicted values into existing RDW methods (such as MPCRed, S2C, TAPF, and ARC) while respecting their internal mechanism in applicable ways. The results of our simulation test and user study demonstrate the significance of future information when using RDW in small physical spaces or complex environments. We prove that the proposed mechanism significantly reduces the number of resets and increases the traveled distance between resets, hence augmenting the redirection performance of all RDW methods explored in this work. Our project and dataset are available at https://github.com/YonseiCGnA-VR/F-RDW.

Redirection Strategy Switching: Selective Redirection Controller for Dynamic Environment Adaptation.

In this paper, we present the Selective Redirection Controller (SRC), which selects the optimal redirection controller based on the physical and virtual environment in Redirected Walking (RDW). The primary advantage of SRC over existing controllers is its dynamic switching among four different redirection controllers (S2C, TAPF, ARC, and SRL) based on the user's environment, as opposed to using a single fixed controller throughout the experience. By switching between redirection controllers based on the context around the user, SRC aims to optimize the advantages of each redirection strategy. The SRC model is trained using reinforcement learning to dynamically and instantaneously switch redirection controllers based on the user's environment. We evaluated the performance of SRC against traditional redirection controllers through simulations and user studies conducted in various physical and virtual environments. The findings indicate that SRC reduces the number of resets significantly compared to traditional redirection controllers. Heat map visualization was utilized during the development process to analyze which redirection controller SRC chooses based on the different environments around the user. SRC alternates between redirection techniques based on the user's environment, maximizing the advantages of each strategy for a superior RDW experience.

Locomotion Techniques for Dynamic Environments: Effects on Spatial Knowledge and User Experiences.

Various locomotion techniques are used to navigate and find way through space in virtual environments (VE), and each technique provides different experiences and performances to users. Previous studies have primarily focused on static environments, whereas there is a need for research from a different perspective of dynamic environments because there are many moving objects in VE, such as other users. In this study, we compare the effects of different locomotion techniques on the user's spatial knowledge and experience, depending on whether the virtual objects are moving or not. The investigated locomotion techniques include joystick, teleportation, and redirected walking (RDW), all commonly used for VR navigation. The results showed that the differences in spatial knowledge and user experience provided by different locomotion techniques can vary depending on whether the environment is static or dynamic. Our results also showed that for a given VE, there are different locomotion techniques that induce fewer collisions between the user and other objects, or reduce the time it takes the user to perform a given task. This study suggests that when designing a locomotion interface for a specific VR application, it is possible to improve the user's spatial knowledge and experience by recommending different locomotion techniques depending on the degree of environment dynamism and and type of task.

MARR : A Multi-Agent Reinforcement Resetter for Redirected Walking.

The reset technique of Redirected Walking (RDW) forcibly reorients the user's direction overtly to avoid collisions with boundaries, obstacles, or other users in the physical space. However, excessive resetting can decrease the user's sense of immersion and presence. Several RDW studies have been conducted to address this issue. Among them, much research has been done on reset techniques that reduce the number of resets by devising reset direction rules or optimizing them for a given environment. However, existing optimization studies on reset techniques have mainly focused on a single-user environment. In a multi-user environment, the dynamic movement of other users and static obstacles in the physical space increase the possibility of resetting. In this study, we propose Multi-Agent Reinforcement Resetter (MARR), which resets the user taking into account both physical obstacles and multi-user movement to minimize the number of resets. MARR is trained using multi-agent reinforcement learning to determine the optimal reset direction in different environments. This approach allows MARR to effectively account for different environmental contexts, including arbitrary physical obstacles and the dynamic movements of other users in the same physical space. We compared MARR to other reset technologies through simulation tests and user studies, and found that MARR outperformed the existing methods. MARR improved performance by learning the optimal reset direction for each subtle technique used in training. MARR has the potential to be applied to new subtle techniques proposed in the future. Overall, our study confirmed that MARR is an effective reset technique in multi-user environments.

Efficacy of White Spot Syndrome Virus Protein VP28-Expressing Chlorella vulgaris as an Oral Vaccine for Shrimp.

The white spot syndrome virus (WSSV) is the causative agent of white spot disease, which kills shrimp within a few days of infection. Although WSSV has a mortality rate of almost 100% and poses a serious threat to the shrimp farming industry, strategies for its prevention and treatment are extremely limited. In this study, we examined the efficacy of VP28, a recombinant WSSV protein expressed in Chlorella vulgaris (C. vulgaris), as an oral shrimp vaccine. When compared with the control group, in which WSSV had a cumulative mortality of 100%, shrimp treated with 5% VP28-expressing C. vulgaris in their feed only had a 20% cumulative mortality rate 12 days after the WSSV challenge. When compared with the nonvaccinated group, the transcription of anti-lipopolysaccharide factor, C-type lectin, and prophenoloxidase genes, which are involved in shrimp defense against WSSV infection, was upregulated 29.6 fold, 15.4 fold, and 11.5 fold, respectively. These findings highlight C. vulgaris as a potential host for industrial shrimp vaccine production.

"To be or Not to be Me?": Exploration of Self-Similar Effects of Avatars on Social Virtual Reality Experiences.

The growing interest in the self-similarity effect of avatars in virtual reality (VR) has spurred the creation of realistic avatars that closely mirror their users. However, despite extensive research on the self-similarity effect in single-user VR environments, our understanding of its impact in social VR settings remains underdeveloped. This shortfall exists despite the unique socio-psychological phenomena arising from the illusion of embodiment that could potentially alter these effects. To fill this gap, this paper provides an in-depth empirical investigation of how avatars' self-similarity influences social VR experiences. Our research uncovers several notable findings: 1) A high level of avatar self-similarity boosts users' sense of embodiment and social presence but has minimal effects on the overall presence and even slightly hinders immersion. These results are driven by increased self-awareness. 2) Among various factors that contribute to the self-similarity of avatars, voice stands out as a significant influencer of social VR experiences, surpassing other representational factors. 3) The impact of avatar self-similarity shows negligible differences between male and female users. Based on these findings, we discuss the pros and cons of incorporating self-similarity into social VR avatars. Our study serves as a foundation for further research in this field.

Attitudinal analysis of vaccination effects to lead endemic phases.

To achieve endemic phases, repeated vaccinations are necessary. However, individuals may grapple with whether to get vaccinated due to potential side effects. When an individual is already immune due to previous infections or vaccinations, the perceived risk from vaccination is often less than the risk of infection. Yet, repeated rounds of vaccination can lead to avoidance, impeding the establishment of endemic phases. We explore this phenomenon using an individual-based Monte Carlo simulation, validating our findings with game theory. The Nash equilibrium encapsulates individuals' non-cooperative behavior, while the system's optimal value represents the societal benefits of altruistic cooperation. We define the difference between these as the price of anarchy. Our simulations reveal that the price of anarchy must fall below a threshold of 12.47 for endemic phases to be achieved in a steady state. This suggests that for a basic reproduction number of 10, a consistent vaccination rate greater than 89% is required. These findings offer new insights into vaccination-related decision-making and can inform effective strategies to tackle infectious diseases.

Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates.

BACKGROUND: Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres' respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF centre outbreak in which patient 2B was the index case. RESULTS: Comparative genomic analysis revealed the mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Mutations in 23S rRNA, mmpL4, porin locus and tetR genes occurred in isolates from both CF patients. Interestingly, we identified two different spontaneous mutation events at the mycobacterial porin locus: a fusion of two tandem porin paralogs in patient 1S and a partial deletion of the first porin paralog in patient 2B. These genomic changes correlated with reduced porin protein expression, diminished 14C-glucose uptake, slower bacterial growth rates, and enhanced TNF-α induction in mycobacteria-infected THP-1 human cells. Porin gene complementation of porin mutants partly restored 14C-glucose uptake, growth rate and TNF-α levels to those of intact porin strains. CONCLUSIONS: We hypothesize that specific mutations accumulated and maintained over time in M. massiliense, including mutations shared among transmissible strains, collectively lead to more virulent, host adapted lineages in CF patients and other susceptible hosts.

ADP-ribose-acceptor hydrolase 2 ( Arh2 ) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival.

ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), which is expressed in heart and skeletal muscle. ARH2 failed to exhibit any in vitro enzymatic activity. To determine its possible in vivo activities, Arh2 -knockout (KO) and - heterozygous (Het) mice were generated using CRISPR-Cas9. Arh2 -KO mice exhibited decreased cardiac contractility by MRI, echocardiography and dobutamine stress with cardiomegaly and abnormal motor function. Arh2 -Het mice showed results similar to those seen in Arh2 -KO mice except for cardiomegaly. Arh2 -KO and -Het mice and mouse embryonic fibroblasts (MEFs) developed spontaneous tumors and subcutaneous tumors in nude mice. We identified 13 mutations in Arh2 -Het MEFs and heterozygous tumors, corresponding to human ARH2 mutations in cancers obtained from COSMIC. Of interest, the L116R mutation in Arh2 gene plays a critical role in aggressive tumorigenesis in nude mice, corresponding to human ARH2 mutations in stomach adenocarcinoma. Both genders of Arh2 -KO and -Het mice showed increased unexpectedly deaths and decreased survival rate during a 24-month observation, caused by tumor, inflammation, non-inflammation (e.g., cardiomegaly, dental dysplasia), and congenital diseases. Thus, Arh2 plays a pivotal role in cardiac function, tumorigenesis, inflammation, and overall survival.

An ensemble method based on marginal-effect models (EMM) for estimating usual food intake from single-day dietary data and internal/external two-day dietary data.

BACKGROUND: With collection of repeated 24-hour recalls, there exist challenges in usual intake estimation, including infeasibility of multiple dietary assessments, and shortage of non-zero intakes for episodically consumed foods. OBJECTIVES: We developed an ensemble method based on marginal-effect models (EMM), which estimates usual intake distribution using single-day data with internal or external two-day data. METHODS: The performance of the EMM was evaluated and compared with the National Cancer Institute (NCI) method and NCI 1-d method, via simulations with various scenarios and real data analyses of red meat, fish, and protein from Korea National Health and Nutrition Examination Survey (KNHANES). RESULTS: Simulations indicated the EMM (maximum bias of 1.67, 3.17, 8.57, 11.63 for average, median, 75%-tile, 95%-tile, respectively) provided more accurate estimation than the NCI method (maximum bias of 4.18, 9.43, 7.56, 37.43) across various scenarios on intake probability and within-person variation. The EMM showed robust estimation when an insufficient number of people have positive consumption on two days. In simulations with various external variance ratios, the EMM showed similar or superior performance to the NCI 1-d method. The EMM produced more stable estimates of usual intake distributions for red meat, fish, and protein than the two NCI methods. CONCLUSION: The proposed EMM showed substantial improvement over the NCI methods when data contain a relatively small number of people with positive consumption on two days; is robust when food intake probability is very low or high; and estimates an external variance ratio with relatively low bias.

Validation and Reliability of the Cataract-related Visual Function Questionnaire (CVFQ)

Purpose@#To evaluate the reliability and validity of the Cataract-related Visual Function Questionnaire (CVFQ). @*Methods@#A prospective cross-sectional study of 141 cataract patients was conducted from March 2022 to June 2022. The questionnaire was created based on a literature review and advice from an expert panel. This study determined its construct validity, criterion validity, internal consistency, and test-retest reliability. @*Results@#The CVFQ consists of 15 items distributed among five categories: overall visual quality, overall visual function, distance vision, near vision, and glare. In the exploratory factor analysis of validity, the first three principal components explained 77.8% of the variance. The p-values in the Spearman correlation test comparing the pre- and postoperative total CVFQ score and best-corrected visual acuity (BCVA) were 0.006 and 0.004, respectively. In the reliability analysis, Cronbach’s alpha was > 0.9 for internal consistency and the p-values of each subcategory were all significant in the analysis of test-retest reliability. @*Conclusions@#Our results indicate that the CVFQ is useful for measuring the visual quality and visual function of cataract patients in Korea.

Poly-ADP ribosylation of p21 by tankyrases promotes p21 degradation and regulates cell cycle progression.

p21WAF1/Cip1 acts as a key negative regulator of cell cycle progression, which can form complexes with cyclin-dependent kinases together with specific cyclins to induce cell cycle arrest at specific stages. p21 protein levels have been shown to be regulated primarily through phosphorylation and ubiquitination during various stages of the cell cycle. Although phosphorylation and ubiquitin-dependent proteasomal degradation of p21 have been well established, other post-translational modifications that contribute to regulation of p21 stability and function remain to be further elucidated. Here, we show that p21 degradation and its function are controlled by tankyrases, which are members of the poly(ADP-ribose) polymerase (PARP) protein family. p21 interacts with tankyrases via newly defined tankyrase-binding motifs and is PARylated by tankyrases in vitro and in vivo, suggesting that PARylation is a new post-translational modification of p21. Up-regulation of tankyrases induces ubiquitin-dependent proteasomal degradation of p21 through an E3 ligase RNF146, thus promoting cell cycle progression in the G1/S phase transition. On the contrary, inhibition of tankyrases by knockdown or inhibitor treatment stabilizes p21 protein and leads to cell cycle arrest in the G1 phase. Together, our data demonstrate that tankyrase may function as a new molecular regulator that controls the protein levels of p21 through PARylation-dependent proteasomal degradation. Hence, a novel function of the tankyrase-p21 axis may represent a new avenue for regulating cell cycle progression.

Exploring bacterioplankton communities and their temporal dynamics in the rearing water of a biofloc-based shrimp (Litopenaeus vannamei) aquaculture system.

Biofloc technology (BFT) has recently gained considerable attention as a sustainable method in shrimp aquaculture. In a successful BFT system, microbial communities are considered a crucial component in their ability to both improve water quality and control microbial pathogens. Yet, bacterioplankton diversity in rearing water and how bacterioplankton community composition changes with shrimp growth are rarely documented. In this study, the Pacific white shrimp, Litopenaeus vannamei was cultivated in a greenhouse-enclosed BFT system. Rearing water samples were collected on a weekly basis for 5 months (152 days) and water quality variables such as physicochemical parameters and inorganic nutrients were monitored. In parallel, 16S rRNA gene pyrosequencing was employed to investigate the temporal patterns of rearing-water microbiota. The productivity, survival rate, and feed conversion ratio were 3.2-4.4 kg/m3, 74%-89%, and 1.2-1.3, respectively, representing successful super-intensive cultures. The metataxonomic results indicated a highly dynamic bacterioplankton community, with two major shifts over the culture. Members of the phylum Planctomycetes dominated in rearing water during the early stages, while Actinobacteria dominated during the middle stages, and Chloroflexi and TM7 dominated during the late stages of culture. The bacterioplankton community fluctuated more in the beginning but stabilized as the culture progressed. Intriguingly, we observed that certain bacterioplankton groups dominated in a culture-stage-specific manner; these groups include Rhodobacteraceae, Flavobacteriaceae, Actinobacteria, and Chloroflexi, which either contribute to water quality regulation or possess probiotic potential. Altogether, our results indicate that an operationally successful BFT-based aquaculture system favors the growth and dynamics of specific microbial communities in rearing water. Our study expands the scientific understanding of the practical utilization of microbes in sustainable aquaculture. A thorough understanding of rearing-water microbiota and factors influencing their dynamics will help to establish effective management strategies.

ATP enhances the error-prone ribonucleotide incorporation by the SARS-CoV-2 RNA polymerase.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or COVID-19) has caused a global pandemic. The SARS-CoV-2 RNA genome is replicated by a conserved "core" replication-transcription complex (RTC) containing an error-prone RNA-dependent RNA polymerase holoenzyme (holo-RdRp, nsp12-nsp7-nsp8) and a RNA proofreading nuclease (nsp14-nsp10). Although structures and functions of SARS-CoV-2 holo-RdRp have been extensively studied and ribonucleotide-analog inhibitors, such as Remdesivir, have been treated for COVID-19 patients, the substrate and nucleotide specificity of SARS-CoV-2 holo-RdRp remain unknown. Here, our biochemical analysis of SARS-CoV-2 holo-RdRp reveals that it has a robust DNA-dependent RNA polymerase activity, in addition to its intrinsic RNA-dependent RNA polymerase activity. Strikingly, SARS-CoV-2 holo-RdRp fully extends RNAs with a low-fidelity even when only ATP and pyrimidine nucleotides, in particular CTP, are provided. This ATP-dependent error-prone ribonucleotide incorporation by SARS-CoV-2 holo-RdRp resists excision by the RNA proofreading nuclease in vitro. Our collective results suggest that a physiological concentration of ATP likely contributes to promoting the error-prone incorporation of ribonucleotides and ribonucleotide-analogs by SARS-CoV-2 holo-RdRp and provide a useful foundation to develop ribonucleotide analogs as an effective therapeutic strategy to combat coronavirus-mediated outbreak.

Mercury contamination of sediments in an open coastal area of the Hupo Basin, East Sea, Korea.

Mercury (Hg) contamination in open coastal areas has attracted public concern regarding safe fish consumption and management of the coastal environment, especially in areas of accidental Hg spills on inland coasts. This study investigated the temporal and spatial distribution of Hg in sediments of Youngil Bay and the Hupo Basin, East Sea, Korea; it also discussed the sources and transport of anthropogenic Hg. Hg hot spots were found in the northern Hupo Basin (elevated by 2-3×) and the river mouth area in Youngil Bay (elevated by approximately 70×). The river mouth contamination resulted from the destruction of a dam impounding landfill waste, while the basin contamination was attributed to atmospheric deposition and Hg enrichment associated with increased organic carbon concentrations driven by high biological production in the coastal upwelling area. Spilled Hg was transported to open coastal areas up to 36.6°N.

Top-Down Mass Spectrometry Data Analysis Using TopPIC Suite.

With the advances of mass spectrometry (MS) techniques, top-down MS-based proteomics has gained increasing attention because of its advantages over bottom-up MS in studying complex proteoforms. TopPIC Suite is a widely used software package for top-down MS-based proteoform identification and quantification. Here, we present the methods for top-down MS data analysis using TopPIC Suite.

Studying the Effects of Congruence of Auditory and Visual Stimuli on Virtual Reality Experiences.

Studies in virtual reality (VR) have introduced numerous multisensory simulation techniques for more immersive VR experiences. However, although they primarily focus on expanding sensory types or increasing individual sensory quality, they lack consensus in designing appropriate interactions between different sensory stimuli. This paper explores how the congruence between auditory and visual (AV) stimuli, which are the sensory stimuli typically provided by VR devices, affects the cognition and experience of VR users as a critical interaction factor in promoting multisensory integration. We defined the types of (in)congruence between AV stimuli, and then designed 12 virtual spaces with different types or degrees of congruence between AV stimuli. We then evaluated the presence, immersion, motion sickness, and cognition changes in each space. We observed the following key findings: 1) there is a limit to the degree of temporal or spatial incongruence that can be tolerated, with few negative effects on user experience until that point is exceeded; 2) users are tolerant of semantic incongruence; 3) a simulation that considers synesthetic congruence contributes to the user's sense of immersion and presence. Based on these insights, we identified the essential considerations for designing sensory simulations in VR and proposed future research directions.

Inner Ear Symptoms Are Prevalent in Patients with High Head Abbreviated Injury Scale Scores after Blunt Head Trauma.

INTRODUCTION: The purpose of this article was to determine the prevalence of inner ear symptoms in patients with blunt head trauma and to explore whether the severity of head trauma was associated with the incidence of such symptoms. METHODS: We performed a retrospective review of 56 patients admitted with blunt head trauma who underwent audiovestibular evaluation within 1 month after injury. Two scales were used to measure the severity of trauma; these were the Glasgow Coma Scale (GCS) and the Head Abbreviated Injury Scale (H-AIS). Patients with sensorineural-type hearing loss, or dizziness with nystagmus, were considered to have inner ear symptoms. RESULTS: About half of all patients (45%) with blunt head trauma showed trauma-related inner ear symptoms. Patients with inner ear symptoms were significantly more likely to have H-AIS scores ≥4 than those without inner ear symptoms (p = 0.004), even without concomitant temporal bone fracture (p > 0.05). Also, patients with inner ear symptoms required a statistically significantly longer time (measured from admission) before undergoing their ontological evaluations than did those without such symptoms (p = 0.002), possibly due to prolonged bed rest and use of sedatives. CONCLUSION: Thus, detailed history-taking and early evaluation using trauma scales are essential for all patients suffering from severe head trauma. It may be necessary to initiate early treatment of traumatic inner ear diseases.

Persistent Epithelial Defects Caused by Limbal Deficiency for Various Causes

Purpose@#We report the process of treating persistent corneal epithelial defects due to limbal deficiency in a patient who underwent surgery for ptosis, recurrent pterygium, and senile cataract for 3 weeks.Case summary: A 65‐year‐old male patient underwent cataract surgery 4 months ago and visited this hospital with persistent inflammation of the left cornea that started 2 months ago. The patient underwent blepharoplasty and pterygium surgery at the same time 3 weeks before cataract surgery. At the first visit, severe conjunctival injection and an oval‐shaped corneal epithelial defect with a size of 3 × 5 mm in the center of the cornea were seen. As the result of the eyelid eversion test, fibrotic scar tissue due to the non‐absorbable suture used during the upper eyelid blepharoplasty was observed and surgically removed. The corneal epithelial defect site became smaller, but the atrophy of the corneal stroma was sustained, and the amniotic membrane was tripled and permanent amniotic membrane transplantation was performed. Corneal epithelial defects have improved with postoperative best‐corrected visual acuity of 0.15. @*Conclusions@#Sufficient recovery period between serial multiple surgeries is required to reduce the occurrence of complications like persistent epithelial defects.