Plantago asiatica seed as a protective agent for mitigating metals toxicity on Penaeusvannamei.

Plantago asiatica seeds (PS) are commonly used as a medicinal plant. This study investigates the efficacy of PS against heavy metal toxicity in white shrimp (Penaeus vannamei). After feeding PS diet (5 g/kg) or basal diet (control group) for 7 days, shrimps were exposed to sublethal concentrations of heavy metals in seawater (As: 12 mg/L, Pb: 250 mg/L, Hg: 0.4 mg/L). The 7-day survival observation showed that the survival in groups fed with PS were significantly higher than that in the control group, revealing that dietary PS had the efficacy to mitigate heavy metal toxicity in white shrimp. Under the same feeding condition, white shrimps were exposed to safety dose of heavy metals (1/10 of sublethal concentrations) to understand the mechanism of mitigation. The metal accumulations in haemolymph, gills, hepatopancreas, and muscle tissues as well as the immune, anti-oxidative, stress related gene expressions in haemocytes, gills and hepatopancreas were measured for 14 days. The As accumulation in gills and hepatopancreas of groups fed with PS were significantly lower than those of control group on day 7 and 14, respectively; The Pb concentration in haemolymph of group fed with PS was significantly lower than that of control group on day 7 and 14; The Hg concentration in hepatopancreas of the group fed with PS was significantly lower than that of control group on day 7. Dietary PS could mitigate heavy metal-induced immune suppression, oxidative stress, and stress response by positively regulating immune (proPO I, Toll, IMD), antioxidant (SOD, GST, Trx), and negatively regulating stress response genes (HSP70, MT). The present study demonstrated that dietary PS could protect white shrimp against metal toxicity by reducing metal accumulations and regulating the immune, antioxidant, and stress response gene expressions in specific tissue. Therefore, PS may serve as a beneficial feed additive in the aquaculture.

Effects of Taiwanese indigenous cinnamon (Cinnamomum osmophloeum) leaf hot-water extract on nonspecific immune responses, resistance against Vibrio parahaemolyticus, nonviable cells, and haemocyte subpopulations in white shrimp (Penaeusvannamei).

This study investigated the effects of Cinnamomum osmophloeum leaf hot-water extract (CLWE) on nonspecific immune responses and resistance to Vibrio parahaemolyticus in white shrimp (Penaeus vannamei). Firstly, a cell viability assay demonstrated that the CLWE is safe to white shrimp heamocytes in the concentration of 0-500 mg L-1. Haemocytes incubated in vitro with 10 and 50 mg L-1 of CLWE showed significantly higher response in superoxide anion production, PO activity, and phagocytic activity. In the in vivo trials, white shrimp were fed with 0, 0.5, 1, 5, and 10 g kg-1 CLWE supplemented feeds (designated as CLWE 0, CLWE 0.5, CLWE 1, CLWE 5, and CLWE 10, respectively) over a period of 28 days. In vivo experiments demonstrated that CLWE 0.5 feeding group resulted in the highest total haemocyte count, superoxide anion production, phenoloxidase activity, and phagocytic activity. Moreover, CLWE 0.5 supplemented feed significantly upregulated the clotting system, antimicrobial peptides, pattern recognition receptors, pattern recognition proteins, and antioxidant defences in white shrimp. Furthermore, the shrimp were infected with V. parahaemolyticus injections after 14 days of feeding as challenge test. Based on the challenge test result, both CLWE 0.5 and CLWE 5 demonstrated a strong resistance to V. parahaemolyticus. These two dosages effectively reduced the number of nonviable cells and activated different haemocyte subpopulations. These findings indicated that treatment with CLWE 0.5 could promote nonspecific immune responses, immune-related gene expression, and resistance to V. parahaemolyticus in white shrimp.

Effects of Nutrient Source, Temperature, and Salinity on the Growth and Survival of Three Giant Clam Species (Tridacnidae).

The habitats of giant clams are undergoing environmental changes, and giant clam populations are declining. The present study was conducted to facilitate clam conservation. We conducted three 18-week trials to investigate the effects of nutrient, temperature, and salinity on the growth performance and survival rates (SRs) of juvenile Tridacna noae, adult Tridacna crocea, and subadult Tridacna derasa, respectively. Regarding nutrient sources, no significant differences were observed in shell length gain, specific growth rate, or SR between clams fed with Chaetoceros muelleri or commercial feed (hw nanotip) and those in a control group (juvenile phototrophs). Regarding temperature, clams cultivated at 27 °C exhibited significantly better growth performance and SR than did those cultivated at 19 °C or 31 °C (p < 0.05). By week 6, all clams in the 19 °C and 31 °C groups had died, indicating that suboptimal growth temperatures have severe adverse effects. Regarding salinity, clams cultivated at 34‱ exhibited significantly higher length gains and specific growth rates than did those cultivated at 20‱ or 25‱ (p < 0.05). SR was not significantly affected by salinity. Understanding how environmental factors affect giant clam populations may help researchers devise effective clam conservation strategies.

Effectiveness of Electroencephalography Neurofeedback for Improving Working Memory and Episodic Memory in the Elderly: A Meta-Analysis.

Background and Objective: Existing evidence indicates the potential benefits of electroencephalography neurofeedback (NFB) training for cognitive function. This study aims to comprehensively review all available evidence investigating the effectiveness of NFB on working memory (WM) and episodic memory (EM) in the elderly population. Material and Methods: A systematic search was conducted across five databases to identify clinical trials examining the impact of NFB on memory function in healthy elderly individuals or those with mild cognitive impairment (MCI). The co-primary outcomes focused on changes in WM and EM. Data synthesis was performed using a random-effects meta-analysis. Results: Fourteen clinical trials (n = 284) were included in the analysis. The findings revealed that NFB was associated with improved WM (k = 11, reported as Hedges' g = 0.665, 95% confidence [CI] = 0.473 to 0.858, p < 0.001) and EM (k = 12, 0.595, 0.333 to 0.856, p < 0.001) in the elderly, with moderate effect sizes. Subgroup analyses demonstrated that NFB had a positive impact on both WM and EM, not only in the healthy population (WM: k = 7, 0.495, 0.213 to 0.778, p = 0.001; EM: k = 6, 0.729, 0.483 to 0.976, p < 0.001) but also in those with MCI (WM: k = 6, 0.812, 0.549 to 1.074, p < 0.001; EM: k = 6, 0.503, 0.088 to 0.919, p = 0.018). Additionally, sufficient training time (totaling more than 300 min) was associated with a significant improvement in WM (k = 6, 0.743, 0.510 to 0.976, p < 0.001) and EM (k = 7, 0.516, 0.156 to 0.876, p = 0.005); however, such benefits were not observed in groups with inadequate training time. Conclusions: The results suggest that NFB is associated with enhancement of both WM and EM in both healthy and MCI elderly individuals, particularly when adequate training time (exceeding 300 min) is provided. These findings underscore the potential of NFB in dementia prevention or rehabilitation.

Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis.

Ulcerative colitis, an inflammatory bowel disease, manifests with symptoms such as abdominal pain, diarrhea, and mucopurulent feces. The long non-coding RNA (lncRNA) ANRIL exhibits significantly reduced expression in UC, yet its specific mechanism is unknown. This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF-α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resulted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-mediated inhibition of IL-6 and TNF-α production. Dual luciferase reporter assays revealed the specific binding of miR-191-5p to ANRIL and SATB1. Furthermore, the downregulation of ANRIL promoted DSS-induced colitis in mice. Together, we provide evidence that ANRIL plays a critical role in regulating IL-6 and TNF-α expression in UC by modulating the miR-191-5p/SATB1 axis. Our study provides novel insights into progression and molecular therapeutic strategies in UC.

VISPUR: Visual Aids for Identifying and Interpreting Spurious Associations in Data-Driven Decisions.

Big data and machine learning tools have jointly empowered humans in making data-driven decisions. However, many of them capture empirical associations that might be spurious due to confounding factors and subgroup heterogeneity. The famous Simpson's paradox is such a phenomenon where aggregated and subgroup-level associations contradict with each other, causing cognitive confusions and difficulty in making adequate interpretations and decisions. Existing tools provide little insights for humans to locate, reason about, and prevent pitfalls of spurious association in practice. We propose VISPUR, a visual analytic system that provides a causal analysis framework and a human-centric workflow for tackling spurious associations. These include a CONFOUNDER DASHBOARD, which can automatically identify possible confounding factors, and a SUBGROUP VIEWER, which allows for the visualization and comparison of diverse subgroup patterns that likely or potentially result in a misinterpretation of causality. Additionally, weproposea REASONING STORYBOARD, which uses a flow-based approach to illustrate paradoxical phenomena, as well as an interactive DECISION DIAGNOSIS panel that helps ensure accountable decision-making. Through an expert interview and a controlled user experiment, our qualitative and quantitative results demonstrate that the proposed "de-paradox" workflow and the designed visual analytic system are effective in helping human users to identify and understand spurious associations, as well as to make accountable causal decisions.

Effect of nanoclay supported nanosilver on the growth inhibition of aquatic pathogens and immunomodulatory effect in Penaeusvannamei.

Hybrid of nanosilver and nanoscale silicate platelet (AgNSP) is a safe, non-toxic nanomaterial which has been applied in medical use due to its strong antibacterial activity. The application of AgNSP in aquaculture was first proposed in the present study by evaluating the in vitro antibacterial activities against four aquatic pathogens, in vitro effects toward shrimp haemocytes as well as the immune responses and disease resistance in Penaeus vannamei fed with AgNSP for 7 days. For evaluating the antibacterial activities of AgNSP in culture medium, the minimum bactericidal concentration (MBC) values against Aeromonas hydrophila, Edwardsiella tarda, Vibrio alginolyticus and Vibrio parahaemolyticus were 100, 15, 625 and 625 mg/L, respectively. Moreover, the inhibition of pathogen growth over a period of 48 h could be achieved by the appropriate treatment of AgNSP in culturing water. In freshwater containing bacterial size of 103 and 106 CFU/mL, the effective doses of AgNSP against A. hydrophila were 12.5 and 450 mg/L, respectively while the effective doses against E. tarda were 0.2 and 50 mg/L, respectively. In seawater with same bacterial size, the effective doses against V. alginolyticus were 150 and 2000 mg/L, respectively while the effective doses against V. parahaemolyticus were 40 and 1500 mg/L, respectively. For the in vitro immune tests, the superoxide anion production and phenoloxidase activity in haemocytes were elevated after in vitro incubation with 0.5-10 mg/L of AgNSP. In the assessment of dietary supplemental effects of AgNSP (2 g/kg), no negative effect on the survival was found at the end of 7 day feeding trail. In addition, the gene expression of superoxide dismutase, lysozyme and glutathione peroxidase were up-regulated in haemocytes taken from shrimps received AgNSP. The following challenge test against Vibrio alginolyticus showed that the survival of shrimp fed with AgNSP was higher than that of shrimp fed with control diet (p = 0.083). Dietary AgNSP improved the Vibrio resistance of shrimp by increasing 22.7% of survival rate. Therefore, AgNSP could potentially be used as a feed additive in shrimp culture.

Dietary of Lactobacillus paracasei and Bifidobacterium longum improve nonspecific immune responses, growth performance, and resistance against Vibrio parahaemolyticus in Penaeus vannamei.

This study investigated the effects of two probiotics, namely Lactobacillus paracasei and Bifidobacterium longum, as feed additives on growth performance, nonspecific immunity, immune-related gene expression, and disease resistance against Vibrio parahaemolyticus in Penaeus vannamei. The experimental diets were prepared using L. paracasei and B. longum at concentrations of 105 and 107 CFU/g; these diets were referred to as P5, P7, B5, and B7. After 8 weeks of the diets, regarding growth performance, the B7 group showed the highest weight gain rate (890.34 ± 103.65%), special growth rate (4.08 ± 0.19%), and feed conversion rate (1.52 ± 0.19%) compared with the other groups. Moreover, the total hemocyte counts were significantly increased (p < 0.05) in the P7 groups on day 14 during the 28-day feeding trial. The phagocytosis rate in all experimental groups was increased on day 14 and was persistently significantly activated to day 21, especially in the P7 and B5 group. The phagocytic index of the P7 group showed a significant increase on day 14 and persistent activation to day 21. In the analysis of respiratory burst activity and phenoloxidase activity, the P7 and B5 groups showed a significant increase on day 7 and persistent activation to day 21. The expression level of the immune-related genes of superoxide dismutase, clotting protein, Penaeidin2, Penaeidin3, Penaeidin4, anti-LPS factor, crustin, and lysozyme was significantly increased in the experimental groups, especially in the P7 group. Furthermore, the optimum conditions of feed additives were determined in challenge trials conducted using P7 and B5. Shrimps fed P7 and B5 showed an increased survival rate (72.73% and 66.67%) after the V. parahaemolyticus challenge. In sum, the results revealed that B. longum, as a feed additive at 107 CFU/g, enhanced growth performance. L. paracasei at 107 CFU/g and B. longum at 105 CFU/g can enhance nonspecific immune responses and immune-related gene expression, and 107 CFU/g L. paracasei has the highest resistance ability for V. parahaemolyticus. Thus, dietary supplementation with L. paracasei and B. longum may be a valuable approach in white shrimp aquaculture.

Synergistic effects of dietary oxolinic acid combined with oxytetracycline on nonspecific immune responses and resistance against Vibrio parahaemolyticus infection of white shrimp (Penaeus vannamei).

This study investigated the synergistic effects of oxolinic acid (OA) combined with oxytetracycline (OTC) on white shrimp (Penaeus vannamei). Disk diffusion susceptibility testing was performed to analyze the sensitivity of Vibrio alginolyticus and Vibrio parahaemolyticus to different concentrations of OA and OTC. The results revealed that 50 mg OA/L combined with 50 mg OTC/L exhibited stronger antibacterial effects on V. alginolyticus and V. parahaemolyticus. The results of in vitro tests indicated that cotreatment with OA and OTC significantly reduced superoxide anion production and phenoloxidase activity, but not phagocytic activity. Subsequently, feeding trials were performed to investigate the immunomodulatory effects and bioaccumulation of dietary OA combined with OTC on shrimp. The healthy shrimp (15.13 ± 1.02 g) were divided into four groups: control, 100 mg OA/kg combined with 50 mg OTC/kg, 50 mg OA/kg combined with 100 mg OTC/kg, and 50 mg OA/kg combined with 50 mg OTC/kg. The shrimp were sampled to determine innate immunity parameters and residual OA and OTC levels in the muscle during a 28-day feeding regimen; the shrimp were fed the experimental diet from day 1 to day 5 and a commercial diet from day 6 to day 28. Residual OA levels were considerably higher in the group fed 100 mg OA/kg combined with 50 mg OTC/kg compared with the other groups and peaked on day 4. The residual OA levels of all the groups were below the detection limit after without providing OA. The residual OTC levels of the group fed 50 mg OA/kg combined with 100 mg OTC/kg were considerably higher from day 1 to day 4. The residual OTC levels in all the groups decreased rapidly and could not be detected on day 28. The administration of 50 mg OA/kg combined with 100 mg OTC/kg exerted the least effect on the white shrimp. Moreover, the survival rates of the treatment groups after the V. parahaemolyticus challenge were higher than those of the control group, especially the group fed 50 mg OA/kg combined with 100 mg OTC/kg. This result indicated that the synergistic effects of dietary OA and OTC are safe and effective. Combination therapy is a new method of antibiotic use in aquaculture.

Pediatric Training Crisis of Emergency Medicine Residency during the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is an emerging viral disease that has caused a global pandemic. Among emergency department (ED) patients, pediatric patient volume mostly and continuously decreased during the pandemic period. Decreased pediatric patient volume in a prolonged period could results in inadequate pediatric training of Emergency Medicine (EM) residents. We collected data regarding pediatric patients who were first seen by EM resident physicians between 1 February 2019, and 31 January 2021, which was divided into pre-epidemic and epidemic periods by 1 February 2020. A significant reduction in pediatric patients per hour (PPH) of EM residents was noted in the epidemic period (from 1.55 to 0.81, p < 0.001). The average patient number was reduced significantly in the classification of infection (from 9.50 to 4.00, p < 0.001), respiratory system (from 84.00 to 22.00, p < 0.001), gastrointestinal system (from 52.00 to 34.00, p = 0.007), otolaryngology (from 4.00 to 2.00, p = 0.022). Among the diagnoses of infectious disease, the most obvious drop was noted in the diagnosis of influenza and enterovirus infection. Reduced pediatric patient volume affected clinical exposure to pediatric EM training of EM residency. Changes in the proportion of pediatric diseases presented in the ED may induce inadequate experience with common and specific pediatric diseases.

Cervical Spine Pathology Increases the Risk of Rotator Cuff Tear: A Population-Based Cohort Study.

BACKGROUND: Patients with cervical radiculopathy typically present with shoulder pain and weakness; these symptoms are similar to those of rotator cuff disease. Studies investigating cervical spine pathology (CSP) as an independent risk factor for rotator cuff tear (RCT) are lacking in the literature. PURPOSE: To investigate the risk of RCT among patients with CSP who have undergone cervical diskectomy (CD) and to determine whether CD reduces this risk. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The authors queried the Taiwan National Health Insurance Research Database for patients diagnosed with CSP between 2004 and 2008 and followed up until the end of 2010. A control cohort comprised patients without CSP who were age- and sex-matched in a 4-to-1 ratio with patients with CSP through propensity score matching. A Cox multivariate proportional hazards model was applied to analyze the risk factors for RCT. After adjustment for confounders, the authors calculated the hazard ratio (HR) and adjusted HR (aHR) between the study and control cohorts. The effects of CD on the risk of RCT were also analyzed. RESULTS: The study included 3245 patients and 12,980 matched controls. A higher RCT incidence rate was found in the CSP cohort, with an aHR of 1.52 (95% CI, 1.22-1.89; P < .001). Patients with CSP who underwent CD had a risk of RCT similar to that of the controls, with an aHR of 1.65 (95% CI, 0.90-3.03; P > .05). CONCLUSION: Patients with CSP had a 1.52-fold higher risk of RCT than healthy controls. Patients with CSP with CD did not have a high risk of RCT, possibly indicating a protective effect of diskectomy against RCT.

M33 condenses chromatin through nuclear body formation and methylation of both histone H3 lysine 9 and lysine 27.

Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.

Transferrin receptor targeting by de novo sheet extension.

The de novo design of polar protein-protein interactions is challenging because of the thermodynamic cost of stripping water away from the polar groups. Here, we describe a general approach for designing proteins which complement exposed polar backbone groups at the edge of beta sheets with geometrically matched beta strands. We used this approach to computationally design small proteins that bind to an exposed beta sheet on the human transferrin receptor (hTfR), which shuttles interacting proteins across the blood-brain barrier (BBB), opening up avenues for drug delivery into the brain. We describe a design which binds hTfR with a 20 nM Kd, is hyperstable, and crosses an in vitro microfluidic organ-on-a-chip model of the human BBB. Our design approach provides a general strategy for creating binders to protein targets with exposed surface beta edge strands.

Developing a Delphi-Based Comprehensive Core Set from the International Classification of Functioning, Disability, and Health Framework for the Rehabilitation of Patients with Burn Injuries.

Burn injuries cause disability and functional limitations in daily living. In a 2015 fire explosion in Taiwan, 499 young people sustained burn injuries. The construction of an effective and comprehensive rehabilitation program that enables patients to regain their previous function is imperative. The International Classification of Functioning, Disability, and Health (ICF) includes multiple dimensions that can contribute to meeting this goal. An ICF core set was developed in this study for Taiwanese patients with burns. A consensus process using three rounds of the Delphi technique was employed. A multidisciplinary team of 30 experts from various institutions was formed. The questionnaire used in this study comprised 162 ICF second-level categories relevant to burn injuries. A 5-point Likert scale was used, and participants assigned a weight to the effect of each category on daily activities after burns. The consensus among ratings was assessed using Spearman's ρ and semi-interquartile range indices. The core set for post-acute SCI was developed from categories that attained a mean score of ≥4.0 in the third round of the Delphi exercise. The core ICF set contained 68 categories. Of these, 19 comprised the component of body functions, 5 comprised body structures, 37 comprised activities and participation, and 7 comprised environmental factors. This preliminary core set offers a comprehensive system for disability assessment and verification following burn injury. The core set provides information for effective rehabilitation strategy setting for patients with burns. Further feasibility and validation studies are required in the future.

Correction: Psychological impact of mass violence depends on affective tone of media content.

[This corrects the article DOI: 10.1371/journal.pone.0213891.].

StoCast: Stochastic Disease Forecasting With Progression Uncertainty.

Forecasting patients' disease progressions with rich longitudinal clinical data has drawn much attention in recent years due to its impactful application in healthcare and the medical field. Researchers have tackled this problem by leveraging traditional machine learning, statistical techniques and deep learning based models. However, existing methods suffer from either deterministic internal structures or over-simplified stochastic components, failing to deal with complex uncertain scenarios such as progression uncertainty (i.e., multiple possible trajectories) and data uncertainty (i.e., imprecise observations and misdiagnosis). To overcome these major uncertainty issues, we propose a novel deep generative model, Stochastic Disease Forecasting Model (StoCast), along with an associated neural network architecture StoCastNet, that can be trained efficiently via stochastic optimization techniques. Our StoCast model uses internal stochastic components to deal with departures of observed data from patients' true health states, and more importantly, is able to produce a comprehensive estimate of future disease progression trajectories. Based on two public datasets related to Alzheimer's disease and Parkinson's disease, we demonstrate how our StoCast model achieves robust and superior performance than deterministic baseline approaches, and conveys richer information that can potentially assist doctors to make decisions with greater confidence in a complex uncertain scenario.

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors.

Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically designed immunogens. Here, we compared the abilities of three such germline-targeting immunogens against the VRC01-class receptors to activate the targeted B cells in transgenic mice expressing the germline VH of the VRC01 antibody but diverse mouse light chains. Immunogen-specific VRC01-like B cells were isolated at different time points after immunization, their VH and VL genes were sequenced, and the corresponding antibodies characterized. VRC01 B cell sub-populations with distinct cross-reactivity properties were activated by each immunogen, and these differences correlated with distinct biophysical and biochemical features of the germline-targeting immunogens. Our study indicates that the design of effective immunogens to activate B cell receptors leading to protective HIV-1 antibodies will require a better understanding of how the biophysical properties of the epitope and its surrounding surface on the germline-targeting immunogen influence its interaction with the available receptor variants in vivo.

De novo design of ACE2 protein decoys to neutralize SARS-CoV-2.

There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer de novo proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape. Using our novel platform, in less than ten weeks, we engineered, validated, and optimized de novo protein decoys of human angiotensin-converting enzyme 2 (hACE2), the membrane-associated protein that SARS-CoV-2 exploits to infect cells. Our optimized designs are hyperstable de novo proteins (∼18-37 kDa), have high affinity for the SARS-CoV-2 receptor binding domain (RBD) and can potently inhibit the virus infection and replication in vitro. Future refinements to our strategy can enable the rapid development of other therapeutic de novo protein decoys, not limited to neutralizing viruses, but to combat any agent that explicitly interacts with cell surface proteins to cause disease.

FairSight: Visual Analytics for Fairness in Decision Making.

Data-driven decision making related to individuals has become increasingly pervasive, but the issue concerning the potential discrimination has been raised by recent studies. In response, researchers have made efforts to propose and implement fairness measures and algorithms, but those efforts have not been translated to the real-world practice of data-driven decision making. As such, there is still an urgent need to create a viable tool to facilitate fair decision making. We propose FairSight, a visual analytic system to address this need; it is designed to achieve different notions of fairness in ranking decisions through identifying the required actions - understanding, measuring, diagnosing and mitigating biases - that together lead to fairer decision making. Through a case study and user study, we demonstrate that the proposed visual analytic and diagnostic modules in the system are effective in understanding the fairness-aware decision pipeline and obtaining more fair outcomes.