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Fish & Shellfish Immunology Jun 2024Takifugu rubripes is a highly valued cultured fish in Asia, while pathogen infections can result in severe diseases and lead to substantial economic losses. Toll-like...
Takifugu rubripes is a highly valued cultured fish in Asia, while pathogen infections can result in severe diseases and lead to substantial economic losses. Toll-like receptors (TLRs), as pattern recognition receptors, play a crucial role on recognition pathogens and initiation innate immune response. However, the immunological properties of teleost-specific TLR23 remain largely unknown. In this study, we investigated the biological functions of TLR23 (TrTLR23) from T. rubripes, found that TrTLR23 existed in various organs. Following bacterial pathogen challenge, the expression levels of TrTLR23 were significantly increased in immune related organs. TrTLR23 located on the cellular membrane and specifically recognized pathogenic microorganism. Co-immunoprecipitation and antibody blocking analysis revealed that TrTLR23 recruited myeloid differentiation primary response protein (MyD88), thereby mediating the activation of the ERK signaling pathway. Furthermore, in vivo showed that, when TrTLR23 is overexpressed in T. rubripes, bacterial replication in fish tissues is significantly inhibited. Consistently, when TrTLR23 expression in T. rubripes is knocked down, bacterial replication is significantly enhanced. In conclusion, these findings suggested that TrTLR23 played a critical role on mediation TLR23-MyD88-ERK axis against bacterial infection. This study revealed that TLR23 involved in the innate immune mechanism, and provided the foundation for development disease control strategies in teleost.
PubMed: 38942251
DOI: 10.1016/j.fsi.2024.109724 -
Virology Jun 2024An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1...
An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1 with the target cells, and replication. We utilized a previously developed qRT-PCR-based assay to examine the effects of broadly neutralizing antibodies (bNAbs), plasma from vaccine trials, and monoclonal antibodies (mAbs) on virus capture and replication. A panel of bNAbs inhibited primary HIV-1 replication in PBMCs but not virus capture. Plasma from RV144 and RV305 trial vaccinees demonstrated inhibition of virus capture with the HIV-1 subtype prevalent in Thailand. Several RV305 derived V2-specific mAbs inhibited virus replication. One of these RV305 derived V2-specific mAbs inhibited both virus capture and replication, demonstrating that it is possible to elicit antibodies by vaccination that inhibit virus capture and replication. Induction of a combination of such antibodies may be the key to protection from HIV-1 acquisition.
PubMed: 38941746
DOI: 10.1016/j.virol.2024.110158 -
Irish Journal of Medical Science Jun 2024In Irish orthopaedic centres without dedicated spinal services, the care of patients is facilitated through tertiary referral centres in Dublin, Cork & Galway. The...
INTRODUCTION
In Irish orthopaedic centres without dedicated spinal services, the care of patients is facilitated through tertiary referral centres in Dublin, Cork & Galway. The outpatient waiting list for elective spinal opinion remains lengthy and challenging. Previous practice in University Hospital Waterford (UHW) necessitated an assessment with a local non-spinal orthopaedic specialist following a GP referral, incurring up to a 2-year wait prior to subspecialist spinal referral. These patients subsequently incurred a further wait for an appointment at the tertiary referral centre. A novel virtual spine clinic in collaboration with the Mater Misericordiae University Hospital (MMUH) was developed to fast-track this process.
AIMS AND METHODS
A retrospective study was performed to audit efficiency by assessing time to initial consultation and time to virtual consultation, treatment outcomes, and patient satisfaction using an adapted patient-satisfaction questionnaire (PSQ-18) and a semi-structured interview. This study reflected the unique nature of patient experience in this pathway.
RESULTS
The median time from referral to being seen in an in-person rapid access physiotherapist combined orthopaedic clinic was 185 days. The median time from initial consultation to virtual consultation was 36 days. The median time interval from virtual consultation to intervention was 110 days. Twenty percent of patients underwent surgery, 14% were further seen in the MMUH outpatients, 7% managed with the trial of physiotherapy, 7% required no follow-up, and 50% planned for radiologically guided spinal injections.
DISCUSSION AND CONCLUSION
This novel pathway is efficient for orthopaedic units without a dedicated spinal service. This can easily be replicated across other orthopaedic centres with minimal cost implications.
PubMed: 38943033
DOI: 10.1007/s11845-024-03742-1 -
Scientific Reports Jun 2024We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance...
We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance claims data and survey data for care-need certification in a large city, we identified participants who started long-term care. Grouping them based on 22 diseases recorded in the past 6 months using fuzzy c-means clustering, we examined the longitudinal association between clusters and death or care-need level deterioration within 2 years. We analyzed 4,648 participants (median age 83 [interquartile range 78-88] years, female 60.4%) between October 2014 and March 2019 and categorized them into (i) musculoskeletal and sensory, (ii) cardiac, (iii) neurological, (iv) respiratory and cancer, (v) insulin-dependent diabetes, and (vi) unspecified subtypes. The results of clustering were replicated in another city. Compared with the musculoskeletal and sensory subtype, the adjusted hazard ratio (95% confidence interval) for death was 1.22 (1.05-1.42), 1.81 (1.54-2.13), and 1.21 (1.00-1.46) for the cardiac, respiratory and cancer, and insulin-dependent diabetes subtypes, respectively. The care-need levels more likely worsened in the cardiac, respiratory and cancer, and unspecified subtypes than in the musculoskeletal and sensory subtype. In conclusion, distinct clinical subtypes exist among individuals initiating long-term care.
Topics: Humans; Female; Aged; Male; Japan; Cluster Analysis; Aged, 80 and over; Long-Term Care; Prognosis; Neoplasms
PubMed: 38942898
DOI: 10.1038/s41598-024-65699-6 -
Scientific Reports Jun 2024Correctional workers (CWs) report high levels of work stressors, frequent exposures to potentially psychologically traumatic events (PPTEs), and substantial mental...
Correctional workers (CWs) report high levels of work stressors, frequent exposures to potentially psychologically traumatic events (PPTEs), and substantial mental health challenges. There is evidence of associations between sleep disturbances and diverse mental health challenges, including preliminary evidence from public safety personnel; however, replications and extensions would better inform interventions to support mental health. The current study was designed to examine associations between quality of sleep, work stress, and mental health disorders in a sample of diverse CWs employed in a provincial correctional service in Ontario, Canada. Data were analyzed from 943 CWs who participated in the cross-sectional, web-based Ontario Provincial Correctional Worker Mental Health and Well-Being Study conducted from December 2017 to June 2018. Sleep quality indicators included symptoms of insomnia, total hours of sleep per night on work nights and off-shift nights, number of days feeling rested per week, and overall sleep quality. Descriptive statistics, analyses of variance, correlational analyses, and logistic regression were used to examine relationships among sleep quality, stress of shift work, and mental health disorder symptoms. CWs slept an average of 6.0 h per night when working and 7.2 h during off-shift nights. CWs reported waking up feeling rested an average of 2.6 days per week and rated their overall quality of sleep in the fair to poor range. Many CWs (64.9%) screened positive for clinically significant symptoms of insomnia. There were also differences across occupational groups such that CWs working as correctional officers reported the most sleep problems. There were statistically significant relationships between insomnia and mental health disorder symptoms. Higher levels of stress from shift work were associated with worse sleep quality. CWs, especially those working as correctional officers in a provincial prison, reported many indicators consistent with poorer quality of sleep. Poor quality of sleep was also associated with work stress and mental health disorders.
Topics: Humans; Ontario; Male; Adult; Female; Mental Disorders; Middle Aged; Cross-Sectional Studies; Sleep Quality; Occupational Stress; Prisons; Sleep Initiation and Maintenance Disorders; Mental Health; Young Adult; Correctional Facilities Personnel
PubMed: 38942803
DOI: 10.1038/s41598-024-65891-8 -
Journal of Virology Jun 2024Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for an acute musculoskeletal disease in humans. Replication of the viral RNA genome occurs in...
Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for an acute musculoskeletal disease in humans. Replication of the viral RNA genome occurs in specialized membranous replication organelles (ROs) or spherules, which contain the viral replication complex. Initially generated by RNA synthesis-associated plasma membrane deformation, alphavirus ROs are generally rapidly endocytosed to produce type I cytopathic vacuoles (CPV-I), from which nascent RNAs are extruded for cytoplasmic translation. By contrast, CHIKV ROs are poorly internalized, raising the question of their fate and functionality at the late stage of infection. Here, using cryogenic-electron microscopy approaches, we investigate the outcome of CHIKV ROs and associated replication machinery in infected human cells. We evidence the late persistence of CHIKV ROs at the plasma membrane with a crowned protein complex at the spherule neck similar to the recently resolved replication complex. The unexpectedly heterogeneous and large diameter of these compartments suggests a continuous, dynamic growth of these organelles beyond the replication of a single RNA genome. Ultrastructural analysis of surrounding cytoplasmic regions supports that outgrown CHIKV ROs remain dynamically active in viral RNA synthesis and export to the cell cytosol for protein translation. Interestingly, rare ROs with a homogeneous diameter are also marginally internalized in CPV-I near honeycomb-like arrangements of unknown function, which are absent in uninfected controls, thereby suggesting a temporal regulation of this internalization. Altogether, this study sheds new light on the dynamic pattern of CHIKV ROs and associated viral replication at the interface with cell membranes in infected cells.IMPORTANCEThe Chikungunya virus (CHIKV) is a positive-stranded RNA virus that requires specialized membranous replication organelles (ROs) for its genome replication. Our knowledge of this viral cycle stage is still incomplete, notably regarding the fate and functional dynamics of CHIKV ROs in infected cells. Here, we show that CHIKV ROs are maintained at the plasma membrane beyond the first viral cycle, continuing to grow and be dynamically active both in viral RNA replication and in its export to the cell cytosol, where translation occurs in proximity to ROs. This contrasts with the homogeneous diameter of ROs during internalization in cytoplasmic vacuoles, which are often associated with honeycomb-like arrangements of unknown function, suggesting a regulated mechanism. This study sheds new light on the dynamics and fate of CHIKV ROs in human cells and, consequently, on our understanding of the Chikungunya viral cycle.
PubMed: 38940586
DOI: 10.1128/jvi.00368-24 -
Data in Brief Aug 2024Reinforcement learning algorithms are increasingly utilized across diverse domains within power systems. One notable challenge in training and deploying these algorithms...
Reinforcement learning algorithms are increasingly utilized across diverse domains within power systems. One notable challenge in training and deploying these algorithms is the acquisition of large, realistic datasets. It is imperative that these algorithms are trained on extensive, realistic datasets over numerous iterations to ensure optimal performance in real-world scenarios. In pursuit of this goal, we curated a comprehensive dataset capturing electric vehicle (EV) charging details over a span of 29,600 days within a designated parking facility. This dataset encompasses necessary information such as connection times, charging durations, and energy consumption of individual EVs. The methodology involved employing conditional tabular generative adversarial networks (CTGAN) to craft a pool of synthetic dataset from a smaller initial dataset collected from an EV charging facility located on the Caltech campus. Subsequently, multiple post-processing techniques were implemented to extract data from this pool, ensuring compliance with the charging station's capacity constraint while maintaining a realistic daily EV demand profile derived from historical data. Using kernel density estimation (KDE), the distributional characteristics of the historical data, especially concerning the timing of EV connections, were faithfully replicated. The developed dataset is specifically useful in training offline reinforcement learning algorithms.
PubMed: 38939017
DOI: 10.1016/j.dib.2024.110587 -
Frontiers in Physiology 2024Monopterus albus is one of China's renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in aquaculture...
Monopterus albus is one of China's renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%-85.33%, which was significantly higher than that of the other three bait groups ( < 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) ( > 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups ( < 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO -N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups ( < 0.05), there was no significant difference in TAN content among the treatment groups ( > 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups ( < 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups ( > 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, could potentially serve as one of the alternative feeds during the initial stages of juveniles stocking.
PubMed: 38938746
DOI: 10.3389/fphys.2024.1403391 -
Journal of Animal Physiology and Animal... Jun 2024A 50-day feeding trial was conducted to evaluate the effects of mulberry leaf powder water extract (MLE) on the growth performance, immunity, antioxidant, meat quality...
Effects of mulberry leaf powder water extract supplementation on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers.
A 50-day feeding trial was conducted to evaluate the effects of mulberry leaf powder water extract (MLE) on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers. A total of 720 birds (initial body weight 40.07 ± 0.05 g) were randomly distributed into four groups with six replicates per group and 30 birds per replicate. Four diets were formulated with 0% (CON), 200 mg/kg MLE (MLE200), 400 mg/kg MLE (MLE400) and 600 mg/kg MLE (MLE600) supplementation. Results showed that the addition of 200-600 mg/kg MLE to the diet significantly increased the body weight (BW) and average daily weight gain (ADG), but feed to gain ratio (F/G) were linearly decreased (p = 0.045) as dietary MLE increased. Birds fed MLE400 had higher (p < 0.05) total antioxidant capacity (T-AOC), interleukin-10 (Il-10), secretory immunoglobulin A (SIgA) and complement 3 (C3) contents than those fed CON, whereas MLE400 had lower malondialdehyde (MDA) content than CON (p < 0.05). Analysis of 16 S rDNA indicated that supplementation with 200 mg/kg MLE increased the Shannon indices in the caecum (p < 0.05). Supplementation with MLE decreased the abundance of the phylum Proteobacteria and genus Helicobacter, and increased the abundance of the phylum Bacteroidetes in the caecum in broiler chickens (p < 0.05). The drip loss rate in the MLE600 was significantly diminished (p < 0.05), whereas the shear force was significantly elevated (p < 0.05). In summary, dietary supplementation with MLE can effectively improve growth performance, intestinal immunity, serum antioxidant capacity, meat quality and intestinal microbiota of yellow feather broilers. The most appropriate MLE supplementation level was 400 mg/kg. This study provides a practical strategy for the dietary application of MLE in yellow feather broilers.
PubMed: 38937951
DOI: 10.1111/jpn.14010 -
Journal of Molecular Biology Jun 2024A large body of work in the last four decades has revealed the key pillars of HIV-1 transcription control at the initiation and elongation steps. Here, I provide a... (Review)
Review
A large body of work in the last four decades has revealed the key pillars of HIV-1 transcription control at the initiation and elongation steps. Here, I provide a recount of this collective knowledge starting with the genomic elements (DNA and nascent TAR RNA stem-loop) and transcription factors (cellular and the viral transactivator Tat), and later transitioning to the assembly and regulation of transcription initiation and elongation complexes, and the role of chromatin structure. Compelling evidence support a core HIV-1 transcriptional program regulated by the sequential and concerted action of cellular transcription factors and Tat to promote initiation and sustain elongation, highlighting the efficiency of a small virus to take over its host to produce the high levels of transcription required for viral replication. I summarize new advances including the use of CRISPR-Cas9, genetic tools for acute factor depletion, and imaging to study transcriptional dynamics, bursting and the progression through the multiple phases of the transcriptional cycle. Finally, I describe current challenges to future major advances and discuss areas that deserve more attention to both bolster our basic knowledge of the core HIV-1 transcriptional program and open up new therapeutic opportunities.
PubMed: 38936695
DOI: 10.1016/j.jmb.2024.168690