bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Potentials of Blockchain for the Governance of Global Digital Commons
Authors: Rozas David , Tenorio-Fornés Antonio , Hassan Samer
Published: April 2021

In recent years, the increasing need for global coordination has attracted interest in the governance of global-scale commons. In the current context, we observe how online applications are ubiquitous, and how emerging technologies enable new capabilities while reshaping sectors. Thus, it is pertinent to ask: could blockchain technologies facilitate the extension and scaling up of cooperative practices and commons management in this global context? In order to address this question, we propose a focus on the most paradigmatic and widely successful examples of global cooperation: global digital commons. Examples of these are the digital resources maintained by large peer production communities, such as free/libre open source software and Wikipedia. Thus, this article identifies and analyzes the potentialities of blockchain to support the sustainability and management of global digital commons. Our approach draws on Elinor Ostrom’s classic principles for commons governance, although revisiting and adapting these to the more challenging scope of global digital commons. Thus, in this work we identify the affordances which blockchain provides (e.g., tokenization, formalization of rules, transparency or codification of trust) to support the effective management of this type of global commons. As part of our analysis, we provide numerous examples of existing blockchain projects using affordances in line with each principle, as well as potential integrations of such affordances in existing practices of peer production communities. Our analysis shows that, when considering the challenges of managing global commons (e.g., heterogeneity or scale), the potential of blockchain is particularly valuable to explore solutions that: distribute power, facilitate coordination, scale up governance, visibilize traditionally invisible work, monitor and track compliance with rules, define collective agreements, and enable cooperation across communities. These affordances and the subsequent analysis contribute to the emergent debate on blockchain-based forms of governance, first by providing analytical categories for further research, but also by providing a guide for experimentation with the development of blockchain tools to facilitate global cooperation.
Content and Method of Information for Participants in Clinical Studies With Induced Pluripotent Stem Cells (iPSCs)
Authors: Orzechowski Marcin , Schochow Maximilian , Kühl Michael , Steger Florian
Published: April 2021

Research with induced pluripotent stem cells (iPSCs) involves specific ethical challenges, which should be addressed in the informed consent process. Up to now, little concern has been paid to the practice of information in iPSC-clinical studies. In order to fill this research gap, we have searched the documentation of the Research Ethics Committee at Ulm University from the years 2007 to 2019. In our previous research, we have identified 11 items for evaluation of the process of information in iPSC research. We used these items to analyze content and form of information provided for participants in the iPSC studies conducted at Ulm University and Ulm University Hospital in Germany. All analyzed studies provide general information regarding the study’s aim, method, and collection of donor’s personal data and specimen. The information for participants in these studies adheres to general guidelines for research involving human subjects; however, in several areas fails to take into account the specific nature of research with iPSCs. The majority of analyzed studies fail to provide information about possible individual consequences connected with genetic research, such as the possibility of re-identification of the donor or incidental findings acquired during research. Missing is also information about the possibility of future studies involving reproductive research or transplantation of cells and organs. The donor information process in all analyzed studies is conducted in form of the information sheet and oral information. The results of our research show that the process of informed consent in iPSC research should be updated as new developments emerge in this area. However, comprehension of information should not be jeopardized through information overload. Effective communication of essential information requires improved information methods tailored to the needs of participants, such as video animations, interactive consent modules or social media instruments.
Association of Myopia and Genetic Variants of TGFB2-AS1 and TGFBR1 in the TGF-β Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children
Authors: Liu Linjie , He Juan , Lu Xiaoyan , Yuan Yimin , Jiang Dandan , Xiao Haishao , Lin Shudan , Xu Liangde , Chen Yanyan
Published: April 2021

Background

Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.

Methods

A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.

Results

A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P’ = 0.022; dominant: P’ = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P’ = 0.008; dominant: P’ = 0.028; recessive: P’ = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P’ = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P’ = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.

Conclusion

The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.
Mouse Retinal Organoid Growth and Maintenance in Longer-Term Culture
Authors: Völkner Manuela , Kurth Thomas , Schor Jana , Ebner Lynn J. A. , Bardtke Lara , Kavak Cagri , Hackermüller Jörg , Karl Mike O.
Published: April 2021

Using retinal organoid systems, organ-like 3D tissues, relies implicitly on their robustness. However, essential key parameters, particularly retinal growth and longer-term culture, are still insufficiently defined. Here, we hypothesize that a previously optimized protocol for high yield of evenly-sized mouse retinal organoids with low variability facilitates assessment of such parameters. We demonstrate that these organoids reliably complete retinogenesis, and can be maintained at least up to 60 days in culture. During this time, the organoids continue to mature on a molecular and (ultra)structural level: They develop photoreceptor outer segments and synapses, transiently maintain its cell composition for about 5–10 days after completing retinogenesis, and subsequently develop pathologic changes – mainly of the inner but also outer retina and reactive gliosis. To test whether this organoid system provides experimental access to the retina during and upon completion of development, we defined and stimulated organoid growth by activating sonic hedgehog signaling, which in patients and mice in vivo with a congenital defect leads to enlarged eyes. Here, a sonic hedgehog signaling activator increased retinal epithelia length in the organoid system when applied during but not after completion of development. This experimentally supports organoid maturation, stability, and experimental reproducibility in this organoid system, and provides a potential enlarged retina pathology model, as well as a protocol for producing larger organoids. Together, our study advances the understanding of retinal growth, maturation, and maintenance, and further optimizes the organoid system for future utilization.
Methylglyoxal Has Different Impacts on the Fungistatic Roles of Ammonia and Benzaldehyde, and Lactoylglutathione Lyase Is Necessary for the Resistance of Arthrobotrys oligospora to Soil Fungistasis
Authors: Long Xi , He Nian-Min , Tan Li-Xue , Yang Yun-He , Zhou Jia-Peng , Liu Zi-Yi , Mo Ming-He , Liu Tong
Published: April 2021

Biocontrol of root-knot nematode has attracted increasing attention over the past two decades. The inconsistent field performance of biocontrol agents, which is caused by soil fungistasis, often restricts their commercial application. There is still a lack of research on the genes involved in biocontrol fungi response to soil fungistasis, which is important for optimizing practical applications of biocontrol fungi. In this study, the lactoylglutathione lyase-encoding AOL_s00004g335 in the nematophagous fungi Arthrobotrys oligospora was knocked out, and three mutant strains were obtained. The hyphal growth of mutants on the three media was almost the same as that of the wild-type strain, but mutants had slightly higher resistance to NaCl, SDS, and H2O2. Methylglyoxal (MG) significantly increased the resistance of A. oligospora to ammonia, but decreased the resistance to benzaldehyde. Furthermore, the resistance of the mutants to soil fungistasis was largely weakened and MG could not increase the resistance of A. oligospora to soil fungistasis. Our results revealed that MG has different effects on the fungistatic roles of ammonia and benzaldehyde and that lactoylglutathione lyase is very important for A. oligospora to resist soil fungistasis.
Media Use During COVID-19: An Investigation of Negative Effects on the Mental Health of Asian Versus White Americans
Authors: Quintero Johnson Jessie M. , Saleem Muniba , Tang Lu , Ramasubramanian Srividya , Riewestahl Emily
Published: April 2021

The role of media use on mental health distress is particularly concerning during the COVID-19 global pandemic. The vulnerabilities to and experiences of the COVID-19 pandemic in the United States are greatly influenced by racial/ethnic inequalities. The COVID-19 pandemic may present unique mental health challenges for Asian Americans because of racial targeting and limited access to and engagement with mental health care. This present investigation examines whether the association between media use and mental health distress is more pronounced for Asian Americans for whom media messages that document and promote anti-Asian racism are likely to be especially salient and influential. Using a national survey of Asian (n = 524) and White (n = 527) American participants, our findings reveal that racial/ethnic identity interacted with the negative effect of media use on mental health for Asian Americans, but not for White Americans. We also explored whether the effect of media use on mental health was mediated by social and health risk perceptions. Results revealed that even though imagined stigma was associated with mental health distress, it did not mediate the effect of media use on mental health. Health risk perceptions mediated the negative effect of media use on both psychosocial distress and loneliness. Implications for health communication, media studies, and anti-Asian racism are discussed, especially in the context of health crises.
FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study
Authors: Wang Zhiheng , Yuan Min , Xu Chengjie , Zhang Yang , Ying Chunmei , Xiao Xirong
Published: April 2021

Background

As an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM.

Methods

In this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders.

Results

The serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall (P < 0.001), with similar results observed between the corresponding BMI subgroups (P < 0.05). The 2nd (OR 1.224, 95% CI 0.603–2.485), 3rd (OR 2.478, 1.229–5.000), and 4th (OR 3.419, 95% CI 1.626–7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments.

Conclusions

The serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.
Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex
Authors: Brognara Fernanda , Castania Jaci Airton , Kanashiro Alexandre , Dias Daniel Penteado Martins , Salgado Helio Cesar
Published: April 2021

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1β; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.
Monocytic-Myeloid Derived Suppressor Cells of HIV-Infected Individuals With Viral Suppression Exhibit Suppressed Innate Immunity to Mycobacterium tuberculosis
Authors: Namdev Priyanka , Patel Shiv , Sparling Brandi , Garg Ankita
Published: April 2021

Tuberculosis can occur during any stage of Human Immunodeficiency virus 1 (HIV) -infection including times when CD4+ T cell numbers have reconstituted and viral replication suppressed. We have previously shown that CD11b+CD33+CD14+HLA-DR-/lo monocytic myeloid-derived suppressor cells (MDSC) persist in HIV-infected individuals on combined anti-retroviral therapy (cART) and with virologic suppression. The response of MDSC to Mycobacterium tuberculosis (Mtb) is not known. In this study, we compared the anti-mycobacterial activity of MDSC isolated from HIV –infected individuals on cART with virologic suppression (HIV MDSC) and HIV-uninfected healthy controls (HIV (-) MDSC). Compared to HIV (-) MDSC, HIV MDSC produced significantly less quantities of anti-mycobacterial cytokines IL-12p70 and TNFα, and reactive oxygen species when cultured with infectious Mtb or Mtb antigens. Furthermore, HIV MDSC showed changes in the Toll-like receptor and IL-27 signaling, including reduced expression of MyD88 and higher levels of IL-27. Neutralizing IL-27 and overexpression of MyD88 synergistically controlled intracellular replication of Mtb in HIV MDSC. These results demonstrate that MDSC in fully suppressed HIV-infected individuals are permissive to Mtb and exhibit downregulated anti-mycobacterial innate immune activity through mechanisms involving IL-27 and TLR signaling. Our findings suggest MDSC as novel mediators of tuberculosis in HIV-Mtb co-infected individuals with virologic suppression.
Three-Dimensional Model of Sub-Plasmalemmal Ca2+ Microdomains Evoked by the Interplay Between ORAI1 and InsP3 Receptors
Authors: Gil Diana , Guse Andreas H. , Dupont Geneviève
Published: April 2021

Ca2+ signaling plays an essential role in T cell activation, which is a key step to start an adaptive immune response. During the transition from a quiescent to a fully activated state, Ca2+ microdomains characterized by reduced spatial and temporal extents are observed in the junctions between the plasma membrane (PM) and the endoplasmic reticulum (ER). Such Ca2+ responses can also occur in response to T cell adhesion to other cells or extracellular matrix proteins in otherwise unstimulated T cells. These non-TCR/CD3-dependent Ca2+ microdomains rely on d-myo-inositol 1,4,5-trisphosphate (IP3) signaling and subsequent store operated Ca2+ entry (SOCE) via the ORAI/STIM system. The detailed molecular mechanism of adhesion-dependent Ca2+ microdomain formation remains to be fully elucidated. We used mathematical modeling to investigate the spatiotemporal characteristics of T cell Ca2+ microdomains and their molecular regulators. We developed a reaction-diffusion model using COMSOL Multiphysics to describe the evolution of cytosolic and ER Ca2+ concentrations in a three-dimensional ER-PM junction. Equations are based on a previously proposed realistic description of the junction, which is extended to take into account IP3 receptors (IP3R) that are located next to the junction. The first model only considered the ORAI channels and the SERCA pumps. Taking into account the existence of preformed clusters of ORAI1 and STIM2, ORAI1 slightly opens in conditions of a full ER. These simulated Ca2+ microdomains are too small as compared to those observed in unstimulated T cells. When considering the opening of the IP3Rs located near the junction, the local depletion of ER Ca2+ allows for larger Ca2+ fluxes through the ORAI1 channels and hence larger local Ca2+ concentrations. Computational results moreover show that Ca2+ diffusion in the ER has a major impact on the Ca2+ changes in the junction, by affecting the local Ca2+ gradients in the sub-PM ER. Besides pointing out the likely involvement of the spontaneous openings of IP3Rs in the activation of SOCE in conditions of T cell adhesion prior to full activation, the model provides a tool to investigate how Ca2+ microdomains extent and interact in response to T cell receptor activation.
Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model
Authors: Hayford Frank E. A. , Ozturk Mumin , Dolman Robin C. , Blaauw Renee , Nienaber Arista , Loots Du Toit , Brombacher Frank , Smuts Cornelius M. , Parihar Suraj P. , Malan Linda
Published: April 2021

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.
Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes
Authors: Huang Hsin-I. , Jewell Mark L. , Youssef Nourhan , Huang Min-Nung , Hauser Elizabeth R. , Fee Brian E. , Rudemiller Nathan P. , Privratsky Jamie R. , Zhang Junyi J. , Reyes Estefany Y. , Wang Donghai , Taylor Gregory A. , Gunn Michael D. , Ko Dennis C. , Cook Donald N. , Chandramohan Vidyalakshmi , Crowley Steven D. , Hammer Gianna Elena
Published: April 2021

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.
The Expression of Toll-Like Receptor 4 mRNA in PBMCs Is Upregulated in Smokers and Decreases Upon Smoking Cessation
Authors: Yeh Hsin-Yu , Hung Shou-Hung , Chen Su-Chiu , Guo Fei-Ran , Huang Hsien-Liang , Peng Jen-Kuei , Lee Chung-Sheng , Tsai Jaw-Shiun
Published: April 2021

Background

Studies have shown in vitro that cigarette smoke condensate stimulates monocytes to express toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1), and enhances their adhesion to the endothelium. However, the same effects of cigarette smoking have not been explored in vivo. This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs).

Methods

A group of 97 smokers and 62 nonsmokers were enrolled. The RNA from PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of ICAM-1, TNF-α, and TLR4. The same markers in PBMCs of 87 quitters were examined before and at one week, one month, and two months after smoking cessation.

Results

Of the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males (p < 0.0001). The mean (SD) age of the smokers was 43.24 (10.89) years, which was younger than 43.45 (11.41) years of nonsmokers (p < 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers (p < 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers (p < 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers (p < 0.0001) comparing with those in the nonsmokers. The mRNA levels of TLR4 and TNF-α in PBMCs decreased in those who had quit smoking for 2 months (p < 0.0001).

Conclusions

ICAM-1, TNF-α, and TLR4 mRNA expression levels in PBMCs increased in smokers and decreased after being on a smoking cessation program for 2 months. This finding suggested that TLR4 expression may mediate the atherogenic inflammatory process induced by smoking.
Case Report: Activating PIK3CD Mutation in Patients Presenting With Granulomatosis With Polyangiitis
Authors: Lu Meiping , Gu Weizhong , Sheng Yuanjian , Wang Jingjing , Xu Xuefeng
Published: April 2021

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by gain-of-function (GOF) mutations in PIK3CD or PIK3R1 genes. The phenotypes of APDS are highly variable, ranging from asymptomatic adults to profound immunodeficiency causing early death in childhood. Herein, we reported two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as granulomatosis with polyangiitis (GPA). Bronchoscopy showed mucosal nodule lymphoid hyperplasia in the entire airway. Many inflammatory cells infiltrated around the airway and in the lung parenchyma, and numbers of CD3+ T cells and CD20+ B cells were significantly increased, especially CD3+ T cells. Whole exome sequencing showed that they had the E1021K (c.3061 G >A) mutation in the PIK3CD gene. These are the first reported cases of APDS presenting as childhood-onset GPA. Pediatricians should suspect of APDS in the differential diagnosis of children who present with GPA-like symptoms. Additionally, timely and repeated bronchoscopies could contribute to providing an important diagnostic clue for APDS.
Aging-Induced Dysbiosis of Gut Microbiota as a Risk Factor for Increased Listeria monocytogenes Infection
Authors: Alam Mohammad S. , Gangiredla Jayanthi , Hasan Nur A. , Barnaba Tammy , Tartera Carmen
Published: April 2021

Invasive foodborne Listeria monocytogenes infection causes gastroenteritis, septicemia, meningitis, and chorioamnionitis, and is associated with high case-fatality rates in the elderly. It is unclear how aging alters gut microbiota, increases risk of listeriosis, and causes dysbiosis post-infection. We used a geriatric murine model of listeriosis as human surrogate of listeriosis for aging individuals to study the effect of aging and L. monocytogenes infection. Aging and listeriosis-induced perturbation of gut microbiota and disease severity were compared between young-adult and old mice. Young-adult and old mice were dosed intragastrically with L. monocytogenes. Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher Listeria colonization in liver, spleen, and feces. Metagenomics analyses of fecal DNA-sequences showed increase in α-diversity as mice aged, and infection reduced its diversity. The relative abundance of major bacterial phylum like, Bacteroidetes and Firmicutes remained stable over aging or infection, while the Verrucomicrobia phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in Clostridaiceae and Lactobacillaceae bacteria even before infection when compared to uninfected young-adult mice. L. monocytogenes infection increased the abundance of Porphyromonadaceae and Prevotellaceae in young-adult mice, while members of the Ruminococcaceae and Lachnospiraceae family were significantly increased in old mice. The abundance of the genera Blautia and Alistipes were significantly reduced post-infection in young-adult and in old mice as compared to their uninfected counterparts. Butyrate producing, immune-modulating bacterial species, like Pseudoflavonifractor and Faecalibacterium were significantly increased only in old infected mice, correlating with increased intestinal inflammatory mRNA up-regulation from old mice tissue. Histologic analyses of gastric tissues showed extensive lesions in the Listeria-infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like Lactobacillus, Clostridiales, and Akkermansia were only abundant in infected young-adult mice but their abundance diminished in the infected old mice. Listeriosis in old mice enhances the abundance of butyrate-producing inflammatory members of the Ruminococcaceae/Lachnospiraceae bacteria while reducing/eliminating beneficial commensals in the gut. Results of this study indicate that, aging may affect the composition of gut microbiota and increase the risk of invasive L. monocytogenes infection.
Morphological Properties of Gastropod Shells in a Warmer and More Acidic Future Ocean Using 3D Micro-Computed Tomography
Authors: Chatzinikolaou Eva , Keklikoglou Kleoniki , Grigoriou Panos
Published: April 2021

The increased absorption of atmospheric CO2by the ocean reduces pH and affects the carbonate chemistry of seawater, thus interfering with the shell formation processes of marine calcifiers. The present study aims to examine the effects of ocean acidification and warming on the shell morphological properties of two intertidal gastropod species,Nassarius nitidusandColumbella rustica. The experimental treatments lasted for 3 months and combined a temperature increase of 3°C and a pH reduction of 0.3 units. The selected treatments reflected the high emissions (RCP 8.5) “business as usual” scenario of the Intergovernmental Panel on Climate Change models for eastern Mediterranean. The morphological and architectural properties of the shell, such as density, thickness and porosity were examined using 3D micro-computed tomography, which is a technique giving the advantage of calculating values for the total shell (not only at specific points) and at the same time leaving the shells intact.Nassarius nitidushad a lower shell density and thickness and a higher porosity when the pH was reduced at ambient temperature, but the combination of reduced pH and increased temperature did not have a noticeable effect in comparison to the control. The shell ofColumbella rusticawas less dense, thinner and more porous under acidic and warm conditions, but when the temperature was increased under ambient pH the shells were thicker and denser than the control. Under low pH and ambient temperature, shells showed no differences compared to the control. The vulnerability of calcareous shells to ocean acidification and warming appears to be variable among species. Plasticity of shell building organisms as an acclimation action toward a continuously changing marine environment needs to be further investigated focusing on species or shell region specific adaptation mechanisms.
The Role of Vessel Biofouling in the Translocation of Marine Pathogens: Management Considerations and Challenges
Authors: Georgiades Eugene , Scianni Chris , Davidson Ian , Tamburri Mario N. , First Matthew R. , Ruiz Gregory , Ellard Kevin , Deveney Marty , Kluza Daniel
Published: April 2021

Vessel biofouling is a major pathway for the introduction, establishment, and subsequent spread of marine non-indigenous macro-organisms. As a result, national and international regulations and guidelines have been implemented to manage the risks associated with this pathway, yet widespread enforcement and uptake are still in their infancy. By comparison, translocation of marine pathogens by vessel biofouling has received little attention despite a mounting body of evidence highlighting the potential importance of this pathway. Using molluscan pathogens as a model, this paper examines the potential for translocation of marine pathogens via the vessel biofouling pathway by reviewing: (1) examples where vessel biofouling is suspected to be the source pathway of non-indigenous pathogen introduction to new areas, and (2) the association between pathogens known to have detrimental effects on wild and farmed mollusk populations with species known to foul vessels and anthropogenic structures. The available evidence indicates that vessel biofouling is a viable and important pathway for translocating marine pathogens, presenting a risk to marine values (i.e., environmental, economic, social, and cultural). While preventive measures to minimize the translocation of macro-organisms are the most efficient way to minimize the likelihood of associated pathogen translocation, the application of reactive management measures to biofouled vessels, including post-filtration treatment, requires further and explicit consideration.
Leatherback Turtles in the Eastern Gulf of Mexico: Foraging and Migration Behavior During the Autumn and Winter
Authors: Sasso Christopher R. , Richards Paul M. , Benson Scott R. , Judge Michael , Putman Nathan F. , Snodgrass Derke , Stacy Brian A.
Published: April 2021

We deployed 19 satellite tags on foraging adult leatherback turtles, including 17 females and 2 males, captured in the northeastern Gulf of Mexico in 2015, 2018, and 2019 in order to study regional distribution and movements. Prior to our study, limited data were available from leatherbacks foraging in the Gulf of Mexico. Tag deployment durations ranged from 63 to 247 days and turtles exhibited three distinct behavior types: foraging, transiting, or rapidly switching between foraging and transiting. Some females were tracked to nesting beaches in the Caribbean. Most of the leatherbacks remained on and foraged along the west Florida continental shelf whereas a few individuals foraged in waters of the central Gulf of Mexico during the autumn and winter. In addition, migration of adult females through the Yucatan Channel indicate that this is a seasonally important area for Caribbean nesting assemblages.
Adhesive Droplets of Glowworm Snares (Keroplatidae: Arachnocampa spp.) Are a Complex Mix of Organic Compounds
Authors: Wolff Jonas O. , von Byern Janek , Piorkowski Dakota , Fang Jian , Wang Xungai , Adler Lewis , Thomas Donald S. , Hook James M. , Blamires Sean J.
Published: April 2021

Adhesive snares built from silks are fascinating adaptations that have rarely evolved outside spiders. Glowworms (Arachnocampa spp.) are an iconic part of the fauna of Australia and New Zealand that combine the construction of a sticky snare with a bioluminescent lure. Recently, the structure and biomechanical properties of glowworm silk have been studied in detail, but the chemical composition of its adhesive coating, and how it varies between species of Arachnocampa remained unclear, limiting an understanding of the glue function. Here, we studied the chemical composition of the water-soluble fraction of the adhesive droplets from the snares in cave and epigaeic populations of three species of Arachnocampa from mainland Australia, Tasmania, and New Zealand, using a combination of nuclear magnetic resonance and mass spectrometry. We found that glowworm glues comprise a large variety of small organic compounds, with organic acids, amino acids, amino acid derivates, alcohols, urea, and urea derivates being the major fraction, supplemented by small amounts of sugars, fatty acids, and other organic compounds. While there was a general overlap in the compounds detected in the adhesives of all tested Arachnocampa species and populations, the relative amounts differed considerably. We expect that these differences are a product of diet rather than an adaptive response to different environments, but experiments are needed for clarification. The high amount of polar substances and compounds that are hygroscopic at high humidity explains the adhesive properties of the viscous solution and its stability in damp environments. These results contribute to our understanding of the unique prey capture strategy of glowworms. Further, the comparison with convergent spider webs highlights the use of small polar compounds as plasticizers of macro-molecular bioadhesives as a general principle. This may inspire the biomimetic design of novel pressure sensitive adhesives with high performance under high humidity conditions.
A Preliminary Study to Use SUVmax of FDG PET-CT as an Identifier of Lesion for Artificial Intelligence
Authors: Hirata Kenji , Manabe Osamu , Magota Keiichi , Furuya Sho , Shiga Tohru , Kudo Kohsuke
Published: April 2021

Background: Diagnostic reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily diagnostic reports of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) – computed tomography (CT). If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret diagnostic reports. We aimed to clarify whether the lesion can be localized using SUVmax strings.

Methods: The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax = 3.14 was given, the voxels with 3.135 ≤ SUVmax < 3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.

Results: A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax < 2), 79.5% (2 ≤ SUVmax < 5), and 97.8% (5 ≤ SUVmax) of lesions.

Conclusion: In this preliminary study, SUVmax of FDG PET-CT could be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax < 2 were difficult to identify. The proposed method may have potential to make use of diagnostic reports retrospectively for constructing training datasets for AI.
Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model
Authors: Zhu Yuchao , Xu Yanan , Hong Lu , Zhou Chunxue , Chen Jia
Published: April 2021

Toxoplasma gondii, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of T. gondii GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic T. gondii infection was assessed by observing the survival time after challenge with the highly virulent T. gondii RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of T. gondii (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-γ, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4– T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-β1, IL-1β, and the transcription factor factors RORγt, RORα, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (p > 0.05). These effective immune responses had mounted protective immunity against T. gondii infection, with a prolonged survival time (16.80 ± 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic T. gondii infection.
Repulsive Guidance Molecule b Deficiency Induces Gut Microbiota Dysbiosis and Increases the Susceptibility to Intestinal Inflammation in Mice
Authors: Shi Ying , Zhong Lu , Li Yuting , Chen Yanfang , Feng Shufen , Wang Min , Xia Yin , Tang Shaohui
Published: April 2021

Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, Prevotellaceae was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that Prevotellaceae was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated Prevotellaceae loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.
Assembly of Natively Synthesized Dual Chromophores Into Functional Actinorhodopsin
Authors: Chuon Kimleng , Kim So Young , Meas Seanghun , Shim Jin-gon , Cho Shin-Gyu , Kang Kun-Wook , Kim Ji-Hyun , Cho Hyun-Suk , Jung Kwang-Hwan
Published: April 2021

Microbial rhodopsin is a simple solar energy-capturing molecule compared to the complex photosynthesis apparatus. Light-driven proton pumping across the cell membrane is a crucial mechanism underlying microbial energy production. Actinobacteria is one of the highly abundant bacterial phyla in freshwater habitats, and members of this lineage are considered to boost heterotrophic growth via phototrophy, as indicated by the presence of actino-opsin (ActR) genes in their genome. However, it is difficult to validate their function under laboratory settings because Actinobacteria are not consistently cultivable. Based on the published genome sequence of Candidatus aquiluna sp. strain IMCC13023, actinorhodopsin from the strain (ActR-13023) was isolated and characterized in this study. Notably, ActR-13023 assembled with natively synthesized carotenoid/retinal (used as a dual chromophore) and functioned as a light-driven outward proton pump. The ActR-13023 gene and putative genes involved in the chromophore (retinal/carotenoid) biosynthetic pathway were detected in the genome, indicating the functional expression ActR-13023 under natural conditions for the utilization of solar energy for proton translocation. Heterologous expressed ActR-13023 exhibited maximum absorption at 565 nm with practical proton pumping ability. Purified ActR-13023 could be reconstituted with actinobacterial carotenoids for additional light-harvesting. The existence of actinorhodopsin and its chromophore synthesis machinery in Actinobacteria indicates the inherent photo-energy conversion function of this microorganism. The assembly of ActR-13023 to its synthesized chromophores validated the microbial community’s importance in the energy cycle.