bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenomic Analysis of the Phylum Nematoda: Conflicts and Congruences With Morphology, 18S rRNA, and Mitogenomes
Authors: Ahmed Mohammed , Roberts Nickellaus G. , Adediran Funmilola , Smythe Ashleigh B. , Kocot Kevin M. , Holovachov Oleksandr
Published: January 2022

Phylogenetic relationships within many lineages of the phylum Nematoda remain unresolved, despite numerous morphology-based and molecular analyses. We performed several phylogenomic analyses using 286 published genomes and transcriptomes and 19 new transcriptomes by focusing on Trichinellida, Spirurina, Rhabditina, and Tylenchina separately, and by analyzing a selection of species from the whole phylum Nematoda. The phylogeny of Trichinellida supported the division ofTrichinellainto encapsulated and non-encapsulated species and placed them as sister toTrichuris. The Spirurina subtree supported the clades formed by species from Ascaridomorpha and Spiruromorpha respectively, but did not support Dracunculoidea. The analysis of Tylenchina supported a clade that included all sampled species from Tylenchomorpha and placed it as sister to clades that included sampled species from Cephalobomorpha and Panagrolaimomorpha, supporting the hypothesis that postulates the single origin of the stomatostylet. The Rhabditina subtree placed a clade composed of all sampled species from Diplogastridae as sister to a lineage consisting of paraphyletic Rhabditidae, a single representative of Heterorhabditidae and a clade composed of sampled species belonging to Strongylida. It also strongly supported all suborders within Strongylida. In the phylum-wide analysis, a clade composed of all sampled species belonging to Enoplia were consistently placed as sister to Dorylaimia + Chromadoria. The topology of the Nematoda backbone was consistent with previous studies, including polyphyletic placement of sampled representatives of Monhysterida and Araeolaimida.
Do Local Habitat Conditions Affect Estimates of Relative Pollen Productivity and Source Area in Heathlands?
Authors: Bunting Mairi Jane , Farrell Michelle
Published: January 2022

Relative Pollen Productivity is an essential parameter for quantitative reconstruction of past land cover from pollen records, but published studies have produced a range of different values for the same taxa. Heathland habitats have limited plant diversity and strong spatial patterning, therefore are useful case studies to investigate aspects of pollen dispersal and deposition, but the estimated spatial area “sensed” by pollen records in these habitats also varies widely between studies. In this study, we estimate pollen productivity from two different microhabitats in a heathland ecosystem in order to investigate the role of local environmental conditions in any observed differences. Vegetation survey was carried out using the Crackles Bequest Project method, pollen assemblages from moss samples counted using standard methods, and relative pollen productivity and estimated source area derived using Extended R-Value analysis. Analysis of the data suggests that at least two pollen source areas exist at the sites studied, reflecting scales of landscape organisation. Microhabitat does not appear to have a marked effect on estimates of Relative Pollen Productivity in this heathland system. This study confirms earlier findings that the estimates obtained for some taxa from heathlands are substantially different than those from agricultural landscapes, especially Poaceae. The findings suggest that the factors controlling Relative Pollen Productivity are still not fully understood, and that differences between locations may reflect real, habitat-led differences. Further investigation of this parameter, which is central to reconstruction of past land cover from pollen records whether overtly incorporated via an algebraic model or less explicitly present via ecological narrative, biomisation or modern analog approaches, is clearly necessary.
Identification of Six Novel Variants of ACAD8 in Isobutyryl-CoA Dehydrogenase Deficiency With Increased C4 Carnitine Using Tandem Mass Spectrometry and NGS Sequencing
Authors: Zhuang Dan-Yan , Ding Shu-Xia , Wang Fei , Yang Xiang-Chun , Pan Xiao-Li , Bao You-Wei , Zhou Li-ming , Li Hai-bo
Published: January 2022

Isobutyryl-CoA dehydrogenase deficiency (IBDHD, MIM: #611283) is a rare autosomal recessive hereditary disease, which is caused by genetic mutations of acyl-CoA dehydrogenase (ACAD) 8 and associated with valine catabolism. Here, tandem mass spectrometry (MS/MS) was applied to screen 302,993 neonates for inherited metabolic diseases (IMD) in Ningbo of China from 2017 to 2020. The results suggest that 198 newborns (0.7‰) were initially screened positive for IBDHD with C4-Carnitine, and 27 cases (0.1‰) were re-screened positive. Genetic diagnosis was performed on 21 of the 27 cases. Seven compound heterozygous variations, three biallelic variations, and one heterozygous variation of ACAD8 were found with a pathogenicity rate of 33.3% (7/21). In addition, seven biallelic variations, one heterozygous variation of acyl-CoA dehydrogenase short chain (ACADS), and one biallelic variation of acyl-CoA dehydrogenase short/branched chain (ACADSB) was detected. Further research showed that ACAD8 mutations of 11 IBDHD cases distributed in six different exons with total 14 mutation sites. Five of which were known suspected pathogenic sites (c.286G > A, c.553C > T, c.1000C > T, c.409G > A, c.500del) and six were novel mutation sites: c.911A > T, c.904C > T, c.826G > A, c.995T > C, c.1166G > A, c.1165C > T. This finding enriched the mutation spectrum of ACAD8 in IBDHD.
Genetic Parameter Estimation and Genome-Wide Association Study-Based Loci Identification of Milk-Related Traits in Chinese Holstein
Authors: Lu Xubin , Arbab Abdelaziz Adam Idriss , Abdalla Ismail Mohamed , Liu Dingding , Zhang Zhipeng , Xu Tianle , Su Guosheng , Yang Zhangping
Published: January 2022

Accurately estimating the genetic parameters and revealing more genetic variants underlying milk production and quality are conducive to the genetic improvement of dairy cows. In this study, we estimate the genetic parameters of five milk-related traits of cows—namely, milk yield (MY), milk fat percentage (MFP), milk fat yield (MFY), milk protein percentage (MPP), and milk protein yield (MPY)—based on a random regression test-day model. A total of 95,375 test-day records of 9,834 cows in the lower reaches of the Yangtze River were used for the estimation. In addition, genome-wide association studies (GWASs) for these traits were conducted, based on adjusted phenotypes. The heritability, as well as the standard errors, of MY, MFP, MFY, MPP, and MPY during lactation ranged from 0.22 ± 0.02 to 0.31 ± 0.04, 0.06 ± 0.02 to 0.15 ± 0.03, 0.09 ± 0.02 to 0.28 ± 0.04, 0.07 ± 0.01 to 0.16 ± 0.03, and 0.14 ± 0.02 to 0.27 ± 0.03, respectively, and the genetic correlations between different days in milk (DIM) within lactations decreased as the time interval increased. Two, six, four, six, and three single nucleotide polymorphisms (SNPs) were detected, which explained 5.44, 12.39, 8.89, 10.65, and 7.09% of the phenotypic variation in MY, MFP, MFY, MPP, and MPY, respectively. Ten Kyoto Encyclopedia of Genes and Genomes pathways and 25 Gene Ontology terms were enriched by analyzing the nearest genes and genes within 200 kb of the detected SNPs. Moreover, 17 genes in the enrichment results that may play roles in milk production and quality were selected as candidates, including CAMK2G, WNT3A, WNT9A, PLCB4, SMAD9, PLA2G4A, ARF1, OPLAH, MGST1, CLIP1, DGAT1, PRMT6, VPS28, HSF1, MAF1, TMEM98, and F7. We hope that this study will provide useful information for in-depth understanding of the genetic architecture of milk production and quality traits, as well as contribute to the genomic selection work of dairy cows in the lower reaches of the Yangtze River.
Hypoxia-Induced miR-378a-3p Inhibits Osteosarcoma Invasion and Epithelial-to-Mesenchymal Transition via BYSL Regulation
Authors: Zhang Junlei , Tang Haijun , Jiang Xiaohong , Huang Nenggan , Wei Qingjun
Published: January 2022

The bystin-like (BYSL) gene is expressed in a wide range of eukaryotes and is closely associated with tumor progression. However, its function and mechanism in osteosarcoma remain unclear. Herein, the protein expression and clinical role of BYSL in human osteosarcoma tissues were assessed. High expression of BYSL was positively related to the metastasis status and poor patient prognosis. Mechanistically, upregulation of BYSL enhanced Nrf2 expression under hypoxia in osteosarcoma cells. MicroRNAs are important epigenetic regulators of osteosarcoma development. Noteworthy, bioinformatics analysis, dual-luciferase reporter and rescue assays showed that miR-378a-3p inhibited BYSL expression by binding to its 3′-untranslated region. Analysis of miR-378a-3p function under hypoxia and normoxia showed that its upregulation suppressed osteosarcoma cells invasion and inhibited epithelial-to-mesenchymal transition by suppressing BYSL. Collectively, the results show that the miR-378a-3p/BYSL may associate with metastasis risk in osteosarcoma.
A SNARE Protein Identification Method Based on iLearnPlus to Efficiently Solve the Data Imbalance Problem
Authors: Ma Dong , Chen Zhihua , He Zhanpeng , Huang Xueqin
Published: January 2022

Machine learning has been widely used to solve complex problems in engineering applications and scientific fields, and many machine learning-based methods have achieved good results in different fields. SNAREs are key elements of membrane fusion and required for the fusion process of stable intermediates. They are also associated with the formation of some psychiatric disorders. This study processes the original sequence data with the synthetic minority oversampling technique (SMOTE) to solve the problem of data imbalance and produces the most suitable machine learning model with the iLearnPlus platform for the identification of SNARE proteins. Ultimately, a sensitivity of 66.67%, specificity of 93.63%, accuracy of 91.33%, and MCC of 0.528 were obtained in the cross-validation dataset, and a sensitivity of 66.67%, specificity of 93.63%, accuracy of 91.33%, and MCC of 0.528 were obtained in the independent dataset (the adaptive skip dipeptide composition descriptor was used for feature extraction, and LightGBM with proper parameters was used as the classifier). These results demonstrate that this combination can perform well in the classification of SNARE proteins and is superior to other methods.
Accelerating Detection of Variants During COVID-19 Surges by Diverse Technological and Public Health Partnerships: A Case Study From Indonesia
Authors: Pradipta Ariel , Kumaheri Meutia Ayuputeri , Wahyudi Lilik Duwi , Susanto Anindya Pradipta , Agasi Harryyanto Ishaq , Shankar Anuraj H. , Sudarmono Pratiwi
Published: January 2022

Early detection of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) variants and use of data for public health action requires a coordinated, rapid, and high throughput approach to whole genome sequencing (WGS). Currently, WGS output from many low- and middle-income countries (LMIC) has lagged. By fostering diverse partnerships and multiple sequencing technologies, Indonesia accelerated SARS-CoV-2 WGS uploads to GISAID from 1,210 in April 2021 to 5,791 in August 2021, an increase from 11 submissions per day between January to May, to 43 per day between June to August. Turn-around-time from specimen collection to submission decreased from 77 to 5 days, allowing for timely public health decisions. These changes were enabled by establishment of the National Genomic Surveillance Consortium, coordination between public and private sector laboratories with WGS capability, and diversification of sequencing platform technologies. Here we present how diversification on multiple levels enabled a rapid and significant increase of national WGS performance, with potentially valuable lessons for other LMICs.
Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance Against Leishmania mexicana Infection
Authors: Osero Bernard Ong’ondo , Cele Zama , Aruleba Raphael Taiwo , Maine Rebeng A. , Ozturk Mumin , Lutz Manfred B. , Brombacher Frank , Hurdayal Ramona
Published: January 2022

IL-4 and IL-13 cytokines have been associated with a non-healing phenotype in murine leishmaniasis inL. mexicana-infected BALB/c mice as demonstrated in IL-4−/−, IL-13−/−and IL-4Rα-/-global knockout mouse studies. However, it is unclear from the studies which cell-type-specific IL-4/IL-13 signaling mediates protection toL. mexicana. Previous studies have ruled out a role for IL-4-mediated protection on CD4+T cells duringL. mexicanainfections. A candidate for this role may be non-lymphocyte cells, particularly DCs, as was previously shown inL. majorinfections, where IL-4 production drives dendritic cell-IL-12 production thereby mediating a type 1 immune response. However, it is unclear if this IL-4-instruction of type 1 immunity also occurs in CL caused byL. mexicana, since the outcome of cutaneous leishmaniasis often depends on the infectingLeishmaniaspecies. Thus, BALB/c mice with cell-specific deletion of the IL-4Rα on CD11c+DCs (CD11ccreIL-4Rα-/lox) were infected withL. mexicanapromastigotes in the footpad and the clinical phenotype, humoral and cellular immune responses were investigated, compared to the littermate control. Our results show that CL disease progression in BALB/c mice is independent of IL-4Rα signaling on DCs as CD11ccreIL-4Rα-/loxmice had similar footpad lesion progression, parasite loads, humoral responses (IgE, IgG1, IgG 2a/b), and IFN-γ cytokine secretion in comparison to littermate controls. Despite this comparable phenotype, surprisingly, IL-4 production in CD11ccreIL-4Rα-/loxmice was significantly increased with an increasing trend of IL-13 when compared to littermate controls. Moreover, the absence of IL-4Rα signaling did not significantly alter the frequency of CD4 and CD8 lymphocytes nor their activation, or memory phenotype compared to littermate controls. However, these populations were significantly increased in CD11ccreIL-4Rα-/loxmice due to greater total cell infiltration into the lymph node. A similar trend was observed for B cells whereas the recruitment of myeloid populations (macrophages, DCs, neutrophils, and Mo-DCs) into LN was comparable to littermate IL-4Rα-/loxmice. Interestingly, IL-4Rα-deficient bone marrow-derived dendritic cells (BMDCs), stimulated with LPS orL. mexicanapromastigotes in presence of IL-4, showed similar levels of IL-12p70 and IL-10 to littermate controls highlighting that IL-4-mediated DC instruction was not impaired in response toL. mexicana. Similarly, IL-4 stimulation did not affect the maturation or activation of IL-4Rα-deficient BMDCs duringL. mexicanainfection nor their effector functions in production of nitrite and arginine-derived metabolite (urea). Together, this study suggests that IL-4 Rα signaling on DCs is not key in the regulation of immune-mediated protection in mice againstL. mexicanainfection.
Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19
Authors: Jiménez-Cortegana Carlos , Sánchez-Jiménez Flora , Pérez-Pérez Antonio , Álvarez Nerissa , Sousa Alberto , Cantón-Bulnes Luisa , Vilariño-García Teresa , Fuentes Sandra , Martín Salomón , Jiménez Marta , León-Justel Antonio , de la Cruz-Merino Luis , Garnacho-Montero José , Sánchez-Margalet Víctor
Published: January 2022

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.
Preemptive Interferon-α Therapy Could Protect Against Relapse and Improve Survival of Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: Long-Term Results of Two Registry Studies
Authors: Shen Meng-Zhu , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Zhao Xiao-Su , Qin Ya-Zhen , Chang Ying-Jun , Liu Kai-Yan , Huang Xiao-Jun , Mo Xiao-Dong
Published: January 2022

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5–30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4–20.6%) and 3.9% (95%CI, 0.0–17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2–91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4–95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5–77.0%) and 10.4% (95%CI, 3.6–17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.
Differential Regulation of Microglial Activation in Response to Different Degree of Ischemia
Authors: Gao Hao , Ju Furong , Ti Rujuan , Zhang Yue , Zhang Shengxiang
Published: January 2022

Microglia are primary immune cells within the brain and are rapidly activated after cerebral ischemia. The degree of microglial activation is closely associated with the severity of ischemia. However, it remains largely unclear how microglial activation is differentially regulated in response to a different degree of ischemia. In this study, we used a bilateral common carotid artery ligation (BCAL) model and induced different degrees of ischemia by varying the duration of ligation to investigate the microglial response in CX3CR1GFP/+ mice. Confocal microscopy, immunofluorescence staining, RNA sequencing, and qRT-PCR were used to evaluate the de-ramification, proliferation, and differential gene expression associated with microglial activation. Our results showed that 30 min of ischemia induced rapid de-ramification of microglia but did not have significant influence on the microglial density. In contrast, 60 min of ischemia led to a significant decrease in microglial density and more pronounced de-ramification of microglial processes. Importantly, 30 min of ischemia did not induce proliferation of microglia, but 60 min of ischemia led to a marked increase in the density of proliferative microglia. Further analysis utilized transcriptome sequencing showed that microglial activation is differentially regulated in response to different degrees of ischemia. A total of 1,097 genes were differentially regulated after 60 min of ischemia, but only 68 genes were differentially regulated after 30 min of ischemia. Pathway enrichment analysis showed that apoptosis, cell mitosis, immune receptor activity and inflammatory-related pathways were highly regulated after 60 min of ischemia compared to 30 min of ischemia. Multiple microglia-related genes such as Cxcl10, Tlr7, Cd86, Tnfrsf1a, Nfkbia, Tgfb1, Ccl2 and Il-6, were upregulated with prolonged ischemia. Pharmacological inhibition of CSF1 receptor demonstrated that CSF1R signaling pathway contributed to microglial proliferation. Together, these results suggest that the proliferation of microglia is gated by the duration of ischemia and microglia were differentially activated in responding to different degrees of ischemia.
Toll-Like Receptor- and Protein Kinase R-Induced Type I Interferon Sustains Infection of Leishmania donovani in Macrophages
Authors: Dias Bruna T. , Goundry Amy , Vivarini Aislan C. , Costa Tatiana F. R. , Mottram Jeremy C. , Lopes Ulisses G. , Lima Ana Paula C. A.
Published: January 2022

Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis, provoking liver and spleen tissue destruction that is lethal unless treated. The parasite replicates in macrophages and modulates host microbicidal responses. We have previously reported that neutrophil elastase (NE) is required to sustain L. donovani intracellular growth in macrophages through the induction of interferon beta (IFN-β). Here, we show that the gene expression of IFN-β by infected macrophages was reduced by half when TLR4 was blocked by pre-treatment with neutralizing antibodies or in macrophages from tlr2-/- mice, while the levels in macrophages from myd88-/- mice were comparable to those from wild-type C57BL/6 mice. The neutralization of TLR4 in tlr2-/- macrophages completely abolished induction of IFN-β gene expression upon parasite infection, indicating an additive role for both TLRs. Induction of type I interferon (IFN-I), OASL2, SOD1, and IL10 gene expression by L. donovani was completely abolished in macrophages from NE knock-out mice (ela2-/-) or from protein kinase R (PKR) knock-out mice (pkr-/-), and in C57BL/6 macrophages infected with transgenic L. donovani expressing the inhibitor of serine peptidase 2 (ISP2). Parasite intracellular growth was impaired in pkr-/- macrophages but was fully restored by the addition of exogenous IFN-β, and parasite burdens were reduced in the spleen of pkr-/- mice at 7 days, as compared to the 129Sv/Ev background mice. Furthermore, parasites were unable to grow in macrophages lacking TLR3, which correlated with lack of IFN-I gene expression. Thus, L. donovani engages innate responses in infected macrophages via TLR2, TLR4, and TLR3, via downstream PKR, to induce the expression of pro-survival genes in the host cell, and guarantee parasite intracellular development.
A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing
Authors: Mulhearn Ben , Li Danyang , McMorrow Fionnuala , Lu Hui , McHugh Neil J. , Tansley Sarah L.
Published: January 2022

Objectives

Anti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ. We aimed to test a new commercial ELISA and compare with previously obtained protein immunoprecipitation.

Methods

Radio-labelled immunoprecipitation had previously been used to determine the autoantibody status of patients with immune-mediated inflammatory myopathies and several healthy controls. ELISA was undertaken on healthy control and anti-TIF1γ sera and compared to previous immunoprecipitation data.

Results

A total of 110 serum samples were analysed: 42 myositis patients with anti- TIF1γ and 68 autoantibody negative healthy control sera. Anti-TIF1γ was detected by ELISA in 41 out of 42 of the anti-TIF1γ-positive samples by immunoprecipitation, and in none of the healthy controls, giving a sensitivity of 97.6% and specificity of 100%. The false negative rate was 2%.

Conclusion

ELISA is an affordable and time-efficient method which is accurate in detecting anti-TIF1γ.
Hsp90 Levels in Idiopathic Inflammatory Myopathies and Their Association With Muscle Involvement and Disease Activity: A Cross-Sectional and Longitudinal Study
Authors: Štorkánová Hana , Oreská Sabína , Špiritović Maja , Heřmánková Barbora , Bubová Kristýna , Kryštůfková Olga , Mann Heřman , Komarc Martin , Slabý Kryštof , Pavelka Karel , Šenolt Ladislav , Zámečník Josef , Vencovský Jiří , Tomčík Michal
Published: January 2022

Background

Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features.

Methods

Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay.

Results

Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3–40.1] vs 9.8 [7.5–13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations.

Conclusions

Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM.
Flaviviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines
Authors: Pan Yuhong , Cai Wenjun , Cheng Anchun , Wang Mingshu , Yin Zhongqiong , Jia Renyong
Published: January 2022

The innate immune system is the host’s first line of defense against the invasion of pathogens including flavivirus. The programmed cell death controlled by genes plays an irreplaceable role in resisting pathogen invasion and preventing pathogen infection. However, the inflammatory cell death, which can trigger the overflow of a large number of pro-inflammatory cytokines and cell contents, will initiate a severe inflammatory response. In this review, we summarized the current understanding of the innate immune response, inflammatory cell death pathway and cytokine secretion regulation during Dengue virus, West Nile virus, Zika virus, Japanese encephalitis virus and other flavivirus infections. We also discussed the impact of these flavivirus and viral proteins on these biological processes. This not only provides a scientific basis for elucidating the pathogenesis of flavivirus, but also lays the foundation for the development of effective antiviral therapies.
Antigen Specific Humoral and Cellular Immunity Following SARS-CoV-2 Vaccination in ANCA-Associated Vasculitis Patients Receiving B-Cell Depleting Therapy
Authors: Marty Paige K. , Van Keulen Virginia P. , Erskine Courtney L. , Shah Maleeha , Hummel Amber , Stachowitz Michael , Fatis Samantha , Granger Dane , Block Matthew S. , Duarte-García Alí , Warrington Kenneth J. , Theel Elitza S. , Zhou Xian , Zeng Hu , Specks Ulrich , Escalante Patricio , Peikert Tobias
Published: January 2022

Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/μl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.
S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling
Authors: Gong Ningyue , Shi Lei , Bing Xin , Li Hui , Hu Houyang , Zhang Pan , Yang Huiming , Guo Na , Du Hongjie , Xia Ming , Liu Chengcheng
Published: January 2022

Epithelial-mesenchymal transition (EMT) is thought to be involved in the tissue remodeling and long-term inflammatory process of chronic sinusitis (CRS), but the driving mechanism is still unclear. Using high-resolution mass spectrometry, we performed a proteomic screen of CRS nasal mucosal tissue to identify differentially expressed proteins. Data are available via ProteomeXchange with identifier PXD030884. Specifically, we identified S100 calcium binding protein A4 (S100A4), an effective factor in inflammation-related diseases, and its downstream protein closely related to tissue fibrosis collagen type I alpha 1 chain (COL1A1), which suggested its involvement in nasal mucosal tissue remodeling. In addition, stimulation of human nasal epithelial cells (HNEpCs) with lipopolysaccharide (LPS) mimicked the inflammatory environment of CRS and showed that S100A4 is involved in regulating EMT and thus accelerating tissue remodeling in the nasal mucosa, both in terms of increased cell motility and overexpression of mesenchymal-type proteins. Additionally, we further investigated the regulation mechanism of S100A4 involved in EMT in CRS. Our research results show that in the inflammatory environment of CRS nasal mucosal epithelial cells, TCF-4 will target to bind to S100A4 and regulate its transcription. The transcription of S100A4 in turn affects the execution of the important signaling pathway in EMT, the Wnt/GSK-3β/β-catenin pathway, through the TCF-4/β-catenin complex. In conclusion, this study confirmed that the expression of S100A4 was significantly increased during the progressive EMT process of CRS mucosal epithelial cells, and revealed that the transcriptional regulation of S100A4 plays an important role in the occurrence and development of EMT. This finding will help us to better understand the pathogenesis behind the remodeling in CRS patients, and identify target molecules for the treatment of CRS.
Influence of Natural Processes and Bottom Trawling in the Nepheloid Layer Structure Off Vancouver Island (British Columbia, Canada, NE Pacific)
Authors: Arjona-Camas Marta , Puig Pere , De Leo Fabio C. , Garner Grant , Paradis Sarah , Durán Ruth , Palanques Albert
Published: January 2022

Continental margins are transitional areas between the land and the deep ocean where large amounts of particulate matter are supplied, transported, and ultimately deposited in the deep sea. High-energy hydrodynamic processes such as storms, ocean currents, or internal waves and tides, as well as bottom trawling activities contribute to the resuspension and remobilization of these particles. These mechanisms favor their transference from the continental shelf to the continental slope and maintain high concentrations of particulate matter in the water column forming nepheloid layers. The temporal evolution of the hydrographic and nepheloid structure in the upper slope off Vancouver Island (British Columbia, Canada, NE Pacific) was assessed by analyzing 4 months (from mid-August to late-November 2018) of sensor data from Ocean Networks Canada (ONC) NEPTUNE cabled seafloor observatory. The distribution of particulate matter during the study period illustrated a well-defined turbidity structure consisting of surface nepheloid layers (SNLs) at <100 m depth associated to primary and secondary productivity, intermediate nepheloid layers (INLs) between 150 and 300 m depth at the shelf-break and upper slope domain, and bottom nepheloid layers (BNLs) developed at >400 m depth. Moderate storm events occurred during fall when the more intense INLs were recorded at shelf-break depths. However, not all the INLs recorded during this period occurred in coincidence with these storms, indicating that these INL detachments were modulated by a different sediment resuspension mechanism. Analyses of fishing vessel activity during the study period revealed that trawlers operated over the same depth range as these INLs. Our results suggest that, in combination with the regional currents, the presence of continuous fishing along the continental slope off Vancouver Island contributes to the advection of suspended sediment particles, playing a major role in their transfer as nepheloid layers.
Occurrence and Molecular Characterization of Some Parasitic Copepods (Siphonostomatoida: Pandaridae) on Pelagic Sharks in the Mediterranean Sea
Authors: Palomba Marialetizia , Insacco Gianni , Zava Bruno , Santoro Mario
Published: January 2022

Copepods of the family Pandaridae are typically ectoparasites of elasmobranch fishes. They display a cosmopolitan distribution and limited host specificity. Published literature on their occurrence on pelagic sharks in the Mediterranean is scarce, often from the past century, or scattered through fish parasite surveys. Moreover, of the 64 valid pandarid species known at present, molecular data from GenBank exists for only 10 species and there are no data from the Mediterranean. In this study, we begin addressing this knowledge gap by exploring the molecular features of some pandarid copepods (i.e.,Dinemoura latifolia,Echthrogaleus coleoptratus, Pandarus satyrus, andPhyllothyreus cornutus) and their phylogenetic relationships using new material from pelagic sharks (i.e.,Prionace glauca,Isurus oxyrinchus, andCarcharodon carcharias) in the Mediterranean. Genetic distances analysis showed intraspecific variation in the mitochondrial DNA cytochrome oxidasecsubunit 1 (mtDNAcox1) sequences and interspecific variations of 0.001–0.081 and 0.196–0.288, respectively, for the small subunit ribosomal DNA (SSU rDNA) and thecox1 gene locus. Phylogenetic analyses of pandarid copepods based on sequences available in GenBank plus the sequences generated by our study revealed two major clades: the first, with strong nodal support, included species ofPandarus,Phyllothyreus,Pannosus, andPseudopandarus; the second, with weaker nodal support, included species ofAchtheinus,Perissopus,Echtrogaleus, Nesippus, andDinemoura.As most pandarid species are missing from the present analyses, we discuss the limitations of our phylogenetic results. Nevertheless, this study represents a first step toward to yielding new information about the phylogeny of parasitic copepods on pelagic sharks in the Mediterranean.
Bioconstruction and Bioerosion in the Northern Adriatic Coralligenous Reefs Quantified by X-Ray Computed Tomography
Authors: Turicchia Eva , Abbiati Marco , Bettuzzi Matteo , Calcinai Barbara , Morigi Maria Pia , Summers Adam P. , Ponti Massimo
Published: January 2022

The northern Adriatic continental shelf hosts several coralligenous reefs rising from the sedimentary bottom and characterized by three main benthic assemblages, respectively, dominated by algal turfs, encrusting calcareous rhodophyte (ECRs) or erect sponges. Bioconstruction and bioerosion processes have been investigated using recruitment travertine limestone tiles deployed in a random site for each main benthic assemblages off Chioggia, 6.1–14.4 km offshore and 20.2–25.4 m depth. Tiles were retrieved after 3 and 12 years and analyzed by X-ray computed tomography (CT), allowing for non-destructively identifying and quantifying deposited and eroded limestone. The main builders were ECRs, serpulids, bryozoans, barnacles, and the bivalves Anomia ephippium, while the most effective borers were sponges from the genus Cliona and the bivalve Rocellaria dubia. The deposition of limestone after 12 years was greater at the site MR08 dominated by ECRs (12.52 ± 2.22 kg m–2), intermediate at the site P213 dominated by erect sponges (4.20 ± 1.24 kg m–2), and lower in the site P204 dominated by algal turfs (2.20 ± 0.72 kg m–2). At MR08, the deposition rate did not vary much over time (from 1.295 ± 0.270 to 1.080 ± 0.198 kg m–2 a–1), while in the other two sites, it significantly slowed down after the first survey period: from 0.952 ± 0.199 to 0.350 ± 0.103 kg m–2 a–1 at P213, and from 1.470 ± 0.462 to 0.203 ± 0.058 kg m–2 a–1 at P204. The amount of eroded limestone increased with the exposure time, with no significant differences among sites, from 1.13 ± 0.29 to 10.39 ± 1.14 kg m–2 on average at 3 and 12 years, respectively. The bioerosion rate also increased with the exposure time and was slightly higher at MR08 (from 0.682 ± 0.208 to 1.105 ± 0.088 kg m–2 a–1), mostly eroded by Cliona rhodensis in addition to C. viridis, compared to P204 (from 0.267 ± 0.078 to 0.676 ± 0.172 kg m–2 a–1) and P213 (from 0.179 ± 0.065 to 0.816 ± 0.171 kg m–2 a–1). Overall, bioconstruction has overcome the bioerosion processes in 3 years. In 12 years, the estimated net balance was essentially nil at all sites. Combining field experiment and CT analysis, this study provides the first quantification of the bioerosion and bioconstruction processes in the northern Adriatic coralligenous reefs, a fundamental step toward their conservation.
The Thermal and Electronic Properties of the Lateral Janus MoSSe/WSSe Heterostructure
Authors: Shen Zhongliang , Ren Kai , Zheng Ruxing , Huang Zhaoming , Cui Zhen , Zheng Zijun , Wang Li
Published: January 2022

Two-dimensional materials have opened up extensive applications for traditional materials. In particular, heterostructures can further create fantastic performances. In this investigation, the lateral heterostructure was constructed using Janus MoSSe and WSSe monolayers with armchair and zigzag interfaces. Performing first-principles calculations and molecular dynamics simulation method, the thermal stability and the semiconductor characteristics with the type-II band structure to separate the photogenerated charges of such Janus MoSSe/WSSe heterostructure are presented, which suggests the potential application of acting as a photocatalyst for water splitting. Importantly, the asymmetric interface of the Janus MoSSe/WSSe heterostructure can result in natural bending, which limits the heat flow transport. Smaller heat flow and the interfacial thermal resistance of the lateral MoSSe/WSSe heterostructure with a zigzag edge interface are mainly due to suppressed acoustic branches. These structural symmetry and interface-dependent properties show the future applications in photovoltaic and thermoelectric devices.
Associations of Multimodal Analgesia With Postoperative Pain Trajectories and Morphine Consumption After Hepatic Cancer Surgery
Authors: Yeh Chia-Yi , Chang Wen-Kuei , Wu Hsiang-Ling , Chau Gar-Yang , Tai Ying-Hsuan , Chang Kuang-Yi
Published: January 2022

Background

This study aimed to investigate the influential factors of postoperative pain trajectories and morphine consumption after hepatic cancer surgery with a particular interest in multimodal analgesia.

Methods

Patients receiving hepatic cancer surgery at a tertiary medical center were enrolled between 2011 and 2016. Postoperative pain scores and potentially influential factors like patient characteristics and the analgesic used were collected. Latent curve analysis was conducted to investigate predictors of postoperative pain trajectories and a linear regression model was used to explore factors associated with postoperative morphine consumption.

Results

450 patients were collected, the daily pain scores during the first postoperative week ranged from 2.0 to 3.0 on average. Male and higher body weight were associated with more morphine consumption (both P < 0.001) but reduced morphine demand was noted in the elderly (P < 0.001) and standing acetaminophen users (P = 0.003). Longer anesthesia time was associated with higher baseline pain levels (P < 0.001). In contrast, male gender (P < 0.001) and standing non-steroidal anti-inflammatory drugs (NSAIDs) use (P = 0.012) were associated with faster pain resolution over time.

Conclusions

Multimodal analgesia with standing acetaminophen and NSAIDs had benefits of opioid-sparing and faster pain resolution, respectively, to patients receiving hepatic cancer surgery.
Evaluation of Disk Halo Size and Identification of Correlated Factors in Myopic Adults
Authors: Zhao Wuxiao , Zhao Jing , Han Tian , Li Meng , Wang Jifang , Zhou Xingtao
Published: January 2022

This study aimed to evaluate glare source-induced disk halo size and assess its correlation with higher-order aberrations (HOAs), pupillometry findings, and contrast sensitivity in myopic adults (aged 23.8 ± 4.4 years). In this cross-sectional study, 150 eyes of 150 patients were assessed. All patients underwent routine ophthalmic examinations, wavefront aberrometry, halo size measurement, dynamic pupillometry, and contrast sensitivity tests. Spearman's correlation analysis and independent sample t-tests were performed for data analysis. The mean halo radius was 82.5 ± 21.8 and 236.7 ± 52.2 arc min at 5 and 1 cd/m2 luminance levels, respectively. The values were inversely correlated with internal spherical aberration (SA) (r = −0.175, p = 0.032 and r = −0.241, p = 0.003, respectively), but not correlated with spherical equivalent (SE, both p > 0.05). Positive correlations were observed between halo radius and pupil size, contraction amplitude, and dilation speed during pupillary light reflex. Halo radii at 5 and 1 cd/m2 luminance levels were not significantly correlated with the area under the log contrast sensitivity function (r = −0.093, p = 0.258 and r = −0.149, p = 0.069, respectively). The mean halo radius was not clinically different between myopic and healthy eyes at 5 cd/m2 luminance level and did not differ significantly between the high and low-to-moderate myopia at 5 and 1 cd/m2 luminance levels (all p > 0.05). According to a stepwise linear regression model, the internal SA had a negative effect on the halo radius under low photpic condition; the average pupil diameter, internal SA and corneal HOAs played a large role in determining the halo radius under mesopic condition.
Bacillus subtilis BS-15 Effectively Improves Plantaricin Production and the Regulatory Biosynthesis in Lactiplantibacillus plantarum RX-8
Authors: Liu Guorong , Nie Rong , Liu Yangshuo , Li Xue , Duan Jiaojiao , Hao Xu , Shan Yumeng , Zhang Jingying
Published: January 2022

Plantaricin is a broad-spectrum bacteriocin produced by Lactiplantibacillus plantarum with significant food industry application potential. It was found that the plantaricin production of L. plantarum RX-8 was enhanced when co-culturing with Bacillus subtilis BS-15. This study, therefore, set out to explore how B. subtilis BS-15 induces biosynthesis of plantaricin. The effect of co-culturing with B. subtilis BS-15 on cell growth, plantaricin production, quorum-sensing (QS) signal molecule PlnA/autoinducer-2 (AI-2) secretion, as well as plantaricin biosynthesis gene cluster and AI-2 synthesis-associated gene expression, was investigated in bacteriocin-producer L. plantarum RX-8. When L. plantarum RX-8 and B. subtilis BS-15 were co-inoculated in Man–Rogosa–Sharp (MRS) for 20 h at an inoculum ratio of 1:1 (106:106 CFU/ml), the greatest plantaricin output (2,048 AU/ml) was obtained, rising by 32-fold compared with the monoculture of L. plantarum RX-8. Additionally, co-culture increased PlnA-inducing activity and AI-2 activity by 8- and 1.14-fold, respectively, over monoculture. RT-qPCR findings generated every 4 h (4–32 h) demonstrated that B. subtilis BS-15 remarkably improved the transcription of plnABCD and plnEF, and increased pfs and luxS transcription, even when using 200 mM D-ribose, a kind of AI-2 inhibitor. Based on the above findings, co-culturing with B. subtilis BS-15 as an environmental stimulus could activate the plantaricin induction via the PlnA-mediated intraspecies QS system and the AI-2-mediated interspecies QS system. Moreover, the inducing effect of PlnA and AI-2 in co-culture was independent. Differential proteomics analysis of B. subtilis BS-15 in co-culture indicated that bacteriocin-inducing regulatory mechanism may be related to flagellar assembly, peptidoglycan biosynthesis, anaerobic respiration, glycine cleavage system, or thiamin pyrophosphate biosynthesis.