Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study
Background Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. Methods We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. Results There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. Discussion In recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.
Liu et al. (2019) Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study. PeerJ 7:e7274 https://doi.org/10.7717/peerj.7274
Differential expression of AtWAKL10 in response to nitric oxide suggests a putative role in biotic and abiotic stress responses
Plant defense against pathogens and abiotic stresses is regulated differentially by communicating signal transduction pathways in which nitric oxide (NO) plays a key role. Here, we show the biological role of Arabidopsis thaliana wall-associated kinase (AtWAK) Like10 (AtWAKL10) that exhibits greater than a 100-fold change in transcript accumulation in response to the NO donor S-nitroso-L-cysteine (CysNO), identified from high throughput RNA-seq based transcriptome analysis. Loss of AtWAKL10 function showed a similar phenotype to wild type (WT) with, however, less branching. The growth of atwakl10 on media supplemented with oxidative or nitrosative stress resulted in differential results with improved growth following treatment with CysNO but reduced growth in response to S-nitrosoglutatione (GSNO) and methyl-viologen. Further, atwakl10 plants exhibited increased susceptibility to virulent Pseudomonas syringae pv tomato (Pst) DC3000 with a significant increase in pathogen growth and decrease in PR1 transcript accumulation compared to WT overtime. Similar results were found in response to Pst DC3000 avrB, resulting in increased cell death as shown by increased electrolyte leakage in atwakl10. Furthermore, atwakl10 also showed increased reactive oxygen species accumulation following Pst DC3000 avrB inoculation. Promoter analysis of AtWAKL10 showed transcription factor (TF) binding sites for biotic and abiotic stress-related TFs. Further investigation into the role of AtWAKL10 in abiotic stresses showed that following two weeks water-withholding drought condition most of the atwakl10 plants got wilted; however, the majority (60%) of these plants recovered following re-watering. In contrast, in response to salinity stress, atwakl10 showed reduced germination under 150 mM salt stress compared to WT, suggesting that NO-induced AtWAKL10 differentially regulates different abiotic stresses. Taken together, this study further elucidates the importance of NO-induced changes in gene expression and their role in plant biotic and abiotic stress tolerance.
Bot et al. (2019) Differential expression of AtWAKL10 in response to nitric oxide suggests a putative role in biotic and abiotic stress responses. PeerJ 7:e7383 https://doi.org/10.7717/peerj.7383
Towards a barnacle tree of life: integrating diverse phylogenetic efforts into a comprehensive hypothesis of thecostracan evolution
Barnacles and their allies (Thecostraca) are a biologically diverse, monophyletic crustacean group, which includes both intensely studied taxa, such as the acorn and stalked barnacles, as well as cryptic taxa, for example, Facetotecta. Recent efforts have clarified phylogenetic relationships in many different parts of the barnacle tree, but the outcomes of these phylogenetic studies have not yet been combined into a single hypothesis for all barnacles. In the present study, we applied a new “synthesis” tree approach to estimate the first working Barnacle Tree of Life. Using this approach, we integrated phylogenetic hypotheses from 27 studies, which did not necessarily include the same taxa or used the same characters, with hierarchical taxonomic information for all recognized species. This first synthesis tree contains 2,070 barnacle species and subspecies, including 239 barnacle species with phylogenetic information and 198 undescribed or unidentified species. The tree had 442 bifurcating nodes, indicating that 79.3% of all nodes are still unresolved. We found that the acorn and stalked barnacles, the Thoracica, and the parasitic Rhizocephala have the largest amount of published phylogenetic information. About half of the thecostracan families for which phylogenetic information was available were polyphyletic. We queried publicly available geographic occurrence databases for the group, gaining a sense of geographic gaps and hotspots in our phylogenetic knowledge. Phylogenetic information is especially lacking for deep sea and Arctic taxa, but even coastal species are not fully incorporated into phylogenetic studies.
Ewers-Saucedo et al. (2019) Towards a barnacle tree of life: integrating diverse phylogenetic efforts into a comprehensive hypothesis of thecostracan evolution. PeerJ 7:e7387 https://doi.org/10.7717/peerj.7387
Paranoia and conspiracy: group cohesion increases harmful intent attribution in the Trust Game
Current theories argue that hyper-sensitisation of social threat perception is central to paranoia. Affected people often also report misperceptions of group cohesion (conspiracy) but little is known about the cognitive mechanisms underpinning this conspiracy thinking in live interactions. In a pre-registered experimental study, we used a large-scale game theory approach (N > 1,000) to test whether the social cohesion of an opposing group affects paranoid attributions in a mixed online and lab-based sample. Participants spanning the full population distribution of paranoia played as proposers in a modified Trust Game: they were allocated a bonus and chose how much money to send to a pair of responders which was quadrupled before reaching these responders. Responders decided how much to return to the proposers through the same process. Participants played in one of two conditions: against a cohesive group who communicated and arrived at a joint decision, or a non-cohesive group who made independent decisions. After the exchange, proposers rated the extent to which the responders’ decisions were driven by (i) self-interest and (ii) intent to harm. Although the true motives are ambiguous, cohesive responders were reliably rated by participants as being more strongly motivated by intent to harm, indicating that group cohesion affects social threat perception. Highly paranoid participants attributed harmful intent more strongly overall but were equally reactive to social cohesion as other participants. This suggests that paranoia involves a generally lowered threshold for social threat detection but with an intact sensitivity for cohesion-related group characteristics.
Greenburgh et al. (2019) Paranoia and conspiracy: group cohesion increases harmful intent attribution in the Trust Game. PeerJ 7:e7403 https://doi.org/10.7717/peerj.7403
Random allogeneic blood transfusion in pigs: characterisation of a novel experimental model
Background Organ cross-talk describes interactions between a primary affected organ and a secondarily injured remote organ, particularly in lung-brain interactions. A common theory is the systemic distribution of inflammatory mediators that are released by the affected organ and transferred through the bloodstream. The present study characterises the baseline immunogenic effects of a novel experimental model of random allogeneic blood transfusion in pigs designed to analyse the role of the bloodstream in organ cross-talk. Methods After approval of the State and Institutional Animal Care Committee, 20 anesthetized pig were randomized in a donor and an acceptor (each n = 8): the acceptor animals each received high-volume whole blood transfusion from the donor (35–40 ml kg−1). Four animals received balanced electrolyte solution instead of blood transfusion (control group; n = 4). Afterwards the animals underwent extended cardiorespiratory monitoring for eight hours. Post mortem assessment included pulmonary, cerebral and systemic mediators of early inflammatory response (IL-6, TNF-alpha, iNOS), wet to dry ratio, and lung histology. Results No adverse events or incompatibilities occurred during the blood transfusion procedures. Systemic cytokine levels and pulmonary function were unaffected. Lung histopathology scoring did not display relevant intergroup differences. Neither within the lung nor within the brain an up-regulation of inflammatory mediators was detected. High volume random allogeneic blood transfusion in pigs neither impaired pulmonary integrity nor induced systemic, lung, or brain inflammatory response. Conclusion This approach can represent a novel experimental model to characterize the blood-bound transmission in remote organ injury.
Ziebart et al. (2019) Random allogeneic blood transfusion in pigs: characterisation of a novel experimental model. PeerJ 7:e7439 https://doi.org/10.7717/peerj.7439
Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women
Background Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women. Methods A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated. Results The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r = 0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p < 0.01), and Streptococcus (p < 0.01) were significantly higher in the GBS-positive group. Discussion The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.
Mu et al. (2019) Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women. PeerJ 7:e7474 https://doi.org/10.7717/peerj.7474
Conservation of transcriptional elements in the obligate symbiont of the whitefly Bemisia tabaci
Background Bacterial symbiosis is widespread in arthropods, especially in insects. Some of the symbionts undergo a long-term co-evolution with the host, resulting in massive genome decay. One particular consequence of genome decay is thought to be the elimination of transcriptional elements within both the coding region and intergenic sequences. In the whitefly Bemisia tabaci species complex, the obligate symbiont Candidatus Portiera aleyrodidarum is of vital importance in nutrient provision, and yet little is known about the regulatory capacities of it. Methods Portiera genomes of two whitefly species in China were sequenced and assembled. Gene content of these two Portiera genomes was predicted, and then subjected to Kyoto Encyclopedia of Genes and Genomes pathway analysis. Together with two other Portiera genomes from whitefly species available previously, four Portiera genomes were utilized to investigate regulatory capacities of Portiera, focusing on transcriptional elements, including genes related with transcription and functional elements within the intergenic spacers. Results Comparative analyses of the four Portiera genomes of whitefly B. tabaci indicate that the obligate symbionts Portiera is similar in different species of whiteflies, in terms of general genome features and possible functions in the biosynthesis of essential amino acids. The screening of transcriptional factors suggests compromised ability of Portiera to regulate the essential amino acid biosynthesis pathways. Meanwhile, thermal tolerance ability of Portiera is indicated with the detection of a σ32 factor, as well as two predicted σ32 binding sites. Within intergenic spacers, functional elements are predicted, including 37 Shine-Dalgarno sequences and 34 putative small RNAs.
Zhu et al. (2019) Conservation of transcriptional elements in the obligate symbiont of the whitefly Bemisia tabaci. PeerJ 7:e7477 https://doi.org/10.7717/peerj.7477
Risk and prognostic nomograms for hepatocellular carcinoma with newly-diagnosed pulmonary metastasis using SEER data
Purpose This research aimed to identify risk factors of pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) and prognostic factors of patients with PM from HCC at initial diagnosis. Methods Patients diagnosed with HCC between 2010 and 2015 were reviewed retrospectively in the Surveillance, Epidemiology, and End Results (SEER) database. Patients with PM from HCC at initial diagnosis were identified from the entire cohort. Predictors for PM from HCC were identified by multivariate logistic regression analysis. Independent prognostic factors for patients with PM were determined by univariate and multivariate Cox regression analysis. Nomograms were also constructed for quantifying risk of metastasis and overall survival estimation visually. Results Our research included 30,641 patients diagnosed with HCC, of whom 1,732 cases were with PM from HCC at initial diagnosis. The risk factors causing PM from HCC were age (P = 0.001), race (P < 0.001), primary tumor size (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), alpha-fetoprotein (P < 0.001), bone metastasis (P < 0.001), brain metastasis (P < 0.001), and intrahepatic metastasis (P < 0.001). The significantly prognostic factors for overall survival were age (P = 0.014), T stage (P = 0.009), surgical approach (P < 0.001), and chemotherapy (P < 0.001). Harrell’s C-index statistics of two nomograms were 0.768 and 0.687 respectively, indicating satisfactory predictive power. Conclusions This research provided evaluation of risk factors and prognosis for patients with PM from HCC. Two nomograms we developed can be convenient individualized tools to facilitate clinical decision-making.
Ye et al. (2019) Risk and prognostic nomograms for hepatocellular carcinoma with newly-diagnosed pulmonary metastasis using SEER data. PeerJ 7:e7496 https://doi.org/10.7717/peerj.7496
Factors affecting the composition of the gut microbiota, and its modulation
Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.
Hasan et al. (2019) Factors affecting the composition of the gut microbiota, and its modulation. PeerJ 7:e7502 https://doi.org/10.7717/peerj.7502
Exploring the potential of deep-blue autofluorescence for monitoring amyloid fibril formation and dissociation
Protein aggregation into amyloid fibrils has been linked to multiple neurodegenerative disorders. Determining the kinetics of fibril formation, as well as their structural stability are important for the mechanistic understanding of amyloid aggregation. Tracking both fibril association and dissociation is usually performed by measuring light scattering of the solution or fluorescence of amyloid specific dyes, such as thioflavin-T. A possible addition to these methods is the recently discovered deep-blue autofluorescence (dbAF), which is linked to amyloid formation. In this work we explore the potential of this phenomenon to monitor amyloid fibril formation and dissociation, as well as show its possible relation to fibril size rather than amyloid structure.
Ziaunys et al. (2019) Exploring the potential of deep-blue autofluorescence for monitoring amyloid fibril formation and dissociation. PeerJ 7:e7554 https://doi.org/10.7717/peerj.7554