bluuebunny/crossref_metadata_2025 huggingface dataset:
Biogeography and Independent Diversification in the Protist Symbiont Community of Heterotermes tenuis
Authors: De Martini Francesca , Coots Nicole L. , Jasso-Selles Daniel E. , Shevat Jordyn , Ravenscraft Alison , Stiblík Petr , Šobotník Jan , Sillam-Dussès David , Scheffrahn Rudolf H. , Carrijo Tiago F. , Gile Gillian H.
Published: March 2021

The eukaryotic microbiome of “lower” termites is highly stable and host-specific. This is due to the mutually obligate nature of the symbiosis and the direct inheritance of protists by proctodeal trophallaxis. However, vertical transmission is occasionally imperfect, resulting in daughter colonies that lack one or more of the expected protist species. This phenomenon could conceivably lead to regional differences in protist community composition within a host species. Here, we have characterized the protist symbiont community of Heterotermes tenuis (Hagen) (Blattodea: Rhinotermitidae) from samples spanning South and Central America. Using light microscopy, single cell isolation, and amplicon sequencing, we report eight species-level protist phylotypes belonging to four genera in the phylum Parabasalia. The diversity and distribution of each phylotype’s 18S rRNA amplicon sequence variants (ASVs) mostly did not correlate with geographical or host genetic distances according to Mantel tests, consistent with the lack of correlation we observed between host genetic and geographical distances. However, the ASV distances of Holomastigotoides Ht3 were significantly correlated with geography while those of Holomastigotoides Ht1 were significantly correlated with host phylogeny. These results suggest mechanisms by which termite-associated protist species may diversify independently of each other and of their hosts, shedding light on the coevolutionary dynamics of this important symbiosis.
Immune Cell Infiltration-Based Characterization of Triple-Negative Breast Cancer Predicts Prognosis and Chemotherapy Response Markers
Authors: Lv Yufei , Lv Dongxu , Lv Xiaohong , Xing Ping , Zhang Jianguo , Zhang Yafang
Published: March 2021

Breast cancer represents the number one cause of cancer-associated mortality globally. The most aggressive molecular subtype is triple negative breast cancer (TNBC), of which limited therapeutic options are available. It is well known that breast cancer prognosis and tumor sensitivity toward immunotherapy are dictated by the tumor microenvironment. Breast cancer gene expression profiles were extracted from the METABRIC dataset and two TNBC clusters displaying unique immune features were identified. Activated immune cells formed a large proportion of cells in the high infiltration cluster, which correlated to a good prognosis. Differentially expressed genes (DEGs) extracted between two heterogeneous subtypes were used to further explore the underlying immune mechanism and to identify prognostic biomarkers. Functional enrichment analysis revealed that the DEGs were predominately related to some processes involved in activation and regulation of innate immune signaling. Using network analysis, we identified two modules in which genes were selected for further prognostic investigation. Validation by independent datasets revealed that CXCL9 and CXCL13 were good prognostic biomarkers for TNBC. We also performed comparisons between the above two genes and immune markers (CYT, APM, TILs, and TIS), as well as cell checkpoint marker expressions, and found a statistically significant correlation between them in both METABRIC and TCGA datasets. The potential of CXCL9 and CXCL13 to predict chemotherapy sensitivity was also evaluated. We found that the CXCL9 and CXCL13 were good predictors for chemotherapy and their expressions were higher in chemotherapy-responsive patients in contrast to those who were not responsive. In brief, immune infiltrate characterization on TNBC revealed heterogeneous subtypes with unique immune features allowed for the identification of informative and reliable characteristics representative of the local immune tumor microenvironment and were potential candidates to guide the management of TNBC patients.
Genomic Approaches Reveal Pleiotropic Effects in Crossbred Beef Cattle
Authors: Rezende Fernanda M. , Rodriguez Eduardo , Leal-Gutiérrez Joel D. , Elzo Mauricio A. , Johnson Dwain D. , Carr Chad , Mateescu Raluca G.
Published: March 2021

Carcass and meat quality are two important attributes for the beef industry because they drive profitability and consumer demand. These traits are of even greater importance in crossbred cattle used in subtropical and tropical regions for their superior adaptability because they tend to underperform compared to their purebred counterparts. Many of these traits are challenging and expensive to measure and unavailable until late in life or after the animal is harvested, hence unrealistic to improve through traditional phenotypic selection, but perfect candidates for genomic selection. Before genomic selection can be implemented in crossbred populations, it is important to explore if pleiotropic effects exist between carcass and meat quality traits. Therefore, the objective of this study was to identify genomic regions with pleiotropic effects on carcass and meat quality traits in a multibreed Angus–Brahman population that included purebred and crossbred animals. Data included phenotypes for 10 carcass and meat quality traits from 2,384 steers, of which 1,038 were genotyped with the GGP Bovine F-250. Single-trait genome-wide association studies were first used to investigate the relevance of direct additive genetic effects on each carcass, sensory and visual meat quality traits. A second analysis for each trait included all other phenotypes as covariates to correct for direct causal effects from identified genomic regions with pure direct effects on the trait under analysis. Five genomic windows on chromosomes BTA5, BTA7, BTA18, and BTA29 explained more than 1% of additive genetic variance of two or more traits. Moreover, three suggestive pleiotropic regions were identified on BTA10 and BTA19. The 317 genes uncovered in pleiotropic regions included anchoring and cytoskeletal proteins, key players in cell growth, muscle development, lipid metabolism and fat deposition, and important factors in muscle proteolysis. A functional analysis of these genes revealed GO terms directly related to carcass quality, meat quality, and tenderness in beef cattle, including calcium-related processes, cell signaling, and modulation of cell–cell adhesion. These results contribute with novel information about the complex genetic architecture and pleiotropic effects of carcass and meat quality traits in crossbred beef cattle.
Environmentally Driven Color Variation in the Pearl Oyster Pinctada margaritifera var. cumingii (Linnaeus, 1758) Is Associated With Differential Methylation of CpGs in Pigment- and Biomineralization-Related Genes
Authors: Stenger Pierre-Louis , Ky Chin-Long , Reisser Céline M. O. , Cosseau Céline , Grunau Christoph , Mege Mickaël , Planes Serge , Vidal-Dupiol Jeremie
Published: March 2021

Today, it is common knowledge that environmental factors can change the color of many animals. Studies have shown that the molecular mechanisms underlying such modifications could involve epigenetic factors. Since 2013, the pearl oyster Pinctada margaritifera var. cumingii has become a biological model for questions on color expression and variation in Mollusca. A previous study reported color plasticity in response to water depth variation, specifically a general darkening of the nacre color at greater depth. However, the molecular mechanisms behind this plasticity are still unknown. In this paper, we investigate the possible implication of epigenetic factors controlling shell color variation through a depth variation experiment associated with a DNA methylation study performed at the whole genome level with a constant genetic background. Our results revealed six genes presenting differentially methylated CpGs in response to the environmental change, among which four are linked to pigmentation processes or regulations (GART, ABCC1, MAPKAP1, and GRL101), especially those leading to darker phenotypes. Interestingly, the genes perlucin and MGAT1, both involved in the biomineralization process (deposition of aragonite and calcite crystals), also showed differential methylation, suggesting that a possible difference in the physical/spatial organization of the crystals could cause darkening (iridescence or transparency modification of the biomineral). These findings are of great interest for the pearl production industry, since wholly black pearls and their opposite, the palest pearls, command a higher value on several markets. They also open the route of epigenetic improvement as a new means for pearl production improvement.
Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection
Authors: Salinas Tybbysay P. , Garrido Jose L. , Salazar Jacqueline R. , Gonzalez Publio , Zambrano Nicole , Fuentes-Villalobos Francisco , Bravo Felipe , Fica-Leon Victor , Salas-Burgos Alexis , Calvo Mario , Alvarez Raymond , Armien Blas , Barria Maria Ines
Published: March 2021

Background

New World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.

Methods

For this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.

Results

High titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.

Conclusion

A Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.
Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience
Authors: Suri Deepti , Rawat Amit , Jindal Ankur Kumar , Vignesh Pandiarajan , Gupta Anju , Pilania Rakesh Kumar , Joshi Vibhu , Arora Kanika , Kumrah Rajni , Anjani Gummadi , Aggarwal Amita , Phadke Shubha , Aboobacker Fouzia N. , George Biju , Edison Eunice Sindhuvi , Desai Mukesh , Taur Prasad , Gowri Vijaya , Pandrowala Ambreen Abdulwahab , Bhattad Sagar , Kanakia Swati , Gottorno Marco , Ceccherini Isabella , Almeida de Jesus Adriana , Goldbach-Mansky Raphaela , Hershfield Michael S. , Singh Surjit
Published: March 2021

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.

Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.

Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.

Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.

Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.
Enhanced Glycolysis Is Required for Antileishmanial Functions of Neutrophils Upon Infection With Leishmania donovani
Authors: Ohms Mareike , Ferreira Carolina , Busch Hauke , Wohlers Inken , Guerra de Souza Ana Cristina , Silvestre Ricardo , Laskay Tamás
Published: March 2021

Visceral leishmaniasis (VL) is a fatal parasitic disease if untreated. Treatment options of VL diminish due to emerging drug resistance. Although the principal host cells for the multiplication ofLeishmaniaare macrophages, neutrophils are the first cells infected with the parasites rapidly after parasite inoculation.Leishmaniacan survive in neutrophils despite the potent antimicrobial effector functions of neutrophils that can eliminate the parasites. Recently, the growing field of immunometabolism provided strong evidence for the therapeutic potential in targeting metabolic processes as a means of controlling immune effector functions. Therefore, the understanding of the immunometabolic profile of neutrophils duringLeishmaniainfection could provide new promising targets for host-directed therapies against VL. To our knowledge, this is the first study addressing the bioenergetics profile ofL. donovani-infected primary human neutrophils. Transcriptome analysis ofL. donovani-infected neutrophils revealed an early significant upregulation of several glycolytic enzymes. Extracellular flux analysis showed that glycolysis and glycolytic capacity were upregulated inL. donovani-infected neutrophils at 6 h post infection. An increased glucose uptake and accumulation of glycolytic end products were further signs for an elevated glycolytic metabolism inL. donovani-infected neutrophils. At the same time point, oxidative phosphorylation provided NADPH for the oxidative burst but did not contribute to ATP production. Inhibition of glycolysis with 2-DG significantly reduced the survival ofL. donovanipromastigotes in neutrophils and in culture. However, this reduction was due to a direct antileishmanial effect of 2-DG and not a consequence of enhanced antileishmanial activity of neutrophils. To further address the impact of glucose metabolism during the first days of infectionin vivo, we treated C57BL/6 mice with 2-DG prior to infection withL. donovaniand assessed the parasite load one day and seven days post infection. Our results show, that seven days post-infection the parasite load of 2-DG treated animals was significantly higher than in mock treated animals. This data indicates that glycolysis serves as major energy source for antimicrobial effector functions againstL. donovani. Inhibition of glycolysis abrogates important neutrophil effector functions that are necessary the initial control ofLeishmaniainfection.
Human PD-1hiCD8+ T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis
Authors: Higashioka Kazuhiko , Yoshimura Motoki , Sakuragi Takahide , Ayano Masahiro , Kimoto Yasutaka , Mitoma Hiroki , Ono Nobuyuki , Arinobu Yojiro , Kikukawa Makoto , Yamada Hisakata , Horiuchi Takahiko , Akashi Koichi , Niiro Hiroaki
Published: March 2021

Background

Rheumatoid arthritis (RA) is a prototypical autoantibody-driven autoimmune disease in which T-B interactions play a critical role. Recent comprehensive analysis suggests that PD-1+CD8+T cells as well as two distinct IL-21-producing PD-1+CD4+T cell subsets, follicular helper T (Tfh) and peripheral helper T (Tph) cells, are involved in the pathogenesis of RA. Herein, we aimed to clarify a generation mechanism of IL-21-producing CD8+T cells in humans, and to characterize this novel subset in patients with RA.

Methods

CD8+T cells in the peripheral blood (PB) and synovial fluid (SF) of healthy control (HC) and patients with RA were subject to the analysis of IL-21 mRNA and protein. We evaluated the surface marker, cytokine and transcription profiles of IL-21-producing CD8+T cells in HCPB, RAPB and RASF.

Results

IL-21-producing CD8+T cells were enriched in the CD45RA-(memory) PD-1+, especially PD-1hisubpopulation, and IL-12 and IL-21 synergistically induced IL-21 production by naïve CD8+T cells. Memory PD-1hiCD8+T cells in HCPB facilitated plasmablast differentiation and IgG production in an IL-21-dependent manner. In addition, PD-1hiCD8+T cells in RASF and RAPB produced large amounts of IL-21 and were characterized by high levels of CD28, ICOS, CD69, HLA-DR, and CCR2 but not CXCR5. Furthermore, PD-1hiCD8+T cells expressed high levels of transcripts ofMAFandPRDM1, a feature observed in Tph cells.

Conclusions

Identification of IL-21-producing PD-1hiCD8+T cells expands our knowledge of T cell subsets with B helper functions in RA. Selective targeting of these subsets could pave an avenue for the development of novel treatment strategies for this disease.
Novel Predictors and Risk Score of Treatment Failure in Peritoneal Dialysis-Related Peritonitis
Authors: Liu Xiang , Qin Aiya , Zhou Huan , He Xueqin , Cader Shamlin , Wang Sirui , Tang Yi , Qin Wei
Published: March 2021

Objective: Peritonitis is a severe complication in peritoneal dialysis (PD). This study was performed to identify predictors and establish a risk score for treatment failure in peritonitis patients.

Methods: A single-center, retrospective observational study was conducted. The basic demographic characteristics, clinical and laboratory data of all patients with peritonitis during the study period were documented and analyzed. Multivariate logistic regression was applied to examine independent predictors of treatment failure, and a risk prediction score was established.

Results: Three hundred fourteen episodes experienced by 241 patients were included in the final analysis. Logistic regression analysis indicated that PD duration (OR 1.017; P 0.005), fibrinogen (OR 1.327; P 0.021), high-density lipoprotein (OR 0.443; P 0.032), fungal infection (OR 63.413; P < 0.001), intestinal obstruction (OR 5.186, P 0.007), and diabetes mellitus (OR 2.451; P 0.018), hemodialysis history (OR 2.804, P 0.006) were independent predictors of treatment failure. The risk prediction score system showed a good calibration (P > 0.05) and discrimination (AUROC 0.80, P < 0.001).

Conclusions: Fibrinogen, PD duration, fungal infection, hemodialysis history, concurrent intestinal obstruction, or diabetes mellitus were independent risk factors for a poor peritonitis outcome, while the high-density lipoprotein was a protective factor. This novel risk prediction score system may be used to predict a high risk of treatment failure effectively.
Microbiome, Immunosenescence, and Chronic Kidney Disease
Authors: Stavropoulou Elisavet , Kantartzi Konstantia , Tsigalou Christina , Aftzoglou Konstantina , Voidarou Chrysa , Konstantinidis Theocharis , Chifiriuc Mariana Carmen , Thodis Elias , Bezirtzoglou Eugenia
Published: March 2021

The gut microbiome is known as an important predictive tool for perceiving characteristic shifts in disease states. Multiple renal diseases and pathologies seem to be associated with gut dysbiosis which directly affects host homeostasis. The gastrointestinal-kidney dialogue confers interesting information about the pathogenesis of multiple kidney diseases. Moreover, aging is followed by specific shifts in the human microbiome, and gradual elimination of physiological functions predisposes the microbiome to inflammaging, sarcopenia, and disease. Aging is characterized by a microbiota with an abundance of disease-associated pathobionts. Multiple factors such as the immune system, environment, medication, diet, and genetic endowment are involved in determining the age of the microbiome in health and disease. Our present review promotes recently acquired knowledge and is expected to inspire researchers to advance studies and investigations on the involved pathways of the gut microbiota and kidney axis.
Environmental Temperatures Affect the Gastrointestinal Microbes of the Chinese Giant Salamander
Authors: Zhu Lifeng , Zhu Wei , Zhao Tian , Chen Hua , Zhao Chunlin , Xu Liangliang , Chang Qing , Jiang Jianping
Published: March 2021

An increasing number of studies have shown that warming also influences the animal gut microbiome (altering the community structure and decreasing its diversity), which might further impact host fitness. Here, based on an analysis of the stomach and gut (the entire intestine: from the anterior intestine to the cloaca) microbiome in laboratory larva of giant salamanders (Andrias davidianus) under different living water temperatures (5, 15, and 25°C) at two sample time points (80 and 330 days after the acclimation), we investigated the potential effect of temperature on the gastrointestinal microbiome community. We found the significant Interaction between sampling time and temperature, or type (stomach and gut) on Shannon index in the gastrointestinal microbiome of the giant salamanders. We also found the significant difference in Shannon index among temperature groups within the same sample type (stomach or gut) at each sample time. 10% of variation in microbiome community could be explained by temperature alone in the total samples. Both the stomach and gut microbiomes displayed the highest similarity in the microbiome community (significantly lowest pairwise unweighted Unifrac distance) in the 25-degree group between the two sampling times compared to those in the 5-degree and 15-degree groups. Moreover, the salamanders in the 25°C treatment showed the highest food intake and body mess compared to that of other temperature treatments. A significant increase in the abundance of Firmicutes in the gastrointestinal microbiome on day 330 with increasing temperatures might be caused by increased host metabolism and food consumption. Therefore, we speculate that the high environmental temperature might indirectly affect both alpha and beta diversity of the gastrointestinal microbiome.
Yeast Culture Improves Egg Quality and Reproductive Performance of Aged Breeder Layers by Regulating Gut Microbes
Authors: Liu Yuchen , Cheng Xue , Zhen Wenrui , Zeng Dan , Qu Lujiang , Wang Zhong , Ning Zhonghua
Published: March 2021

This study aimed to investigate the effects of dietary yeast culture (YC) supplementation on egg production, egg quality, reproductive performance, immune functions, antioxidant capacity, and intestinal microbial structure of aged hens. A total of 224 Hy-Line Brown layers (54 weeks old) were randomly assigned to two dietary treatments. The control group was fed a basal diet and the YC group was supplemented with YC at 2.0 g/kg of their diet. Each group had seven replicates with 16 hens each. The study was conducted over a period of 8 weeks. Results indicated that YC addition had no significant effect on laying performance. However, it significantly improved egg quality and hatching rate, enhanced ileum crude fat digestibility, increased the serum parameters of lysozyme (LZM) and total antioxidation capacity (T-AOC) (P < 0.05), and reduced serum aspartate aminotransferase (AST) levels (P < 0.05). Using 16S rRNA analysis, we found that addition of YC significantly altered ileum microbial composition. Linear discriminant analysis of effect size (LEfSe) showed significant enrichment of Bacilli and Lactobacilli in the YC group. PICRUSt analysis of the ileal microbiota found that glutathione metabolism, ubiquinone, and other terpenoid-quinone biosynthesis and lipopolysaccharide biosynthesis protein pathways were highly enriched in the YC group compared with the basal diet group. In summary, the addition of YC can improve egg quality, immune functions, antioxidant capacity, reproduction efficiency, and digestive absorption by increasing the abundance of Lactobacilli and Bacilli. Furthermore, it also improves the biosynthesis of lipopolysaccharide proteins, glutathione metabolism, and the synthesis of ubiquinone and other terpenoid-quinone metabolic pathways.
Comparison of Microbial Communities in Colorado Potato Beetles (Leptinotarsa decemlineata Say) Collected From Different Sources in China
Authors: Yu Yanxue , Wang Yuhan , Li Hongwei , Yu Xin , Shi Wangpeng , Zhai Junfeng
Published: March 2021

Microbial communities in insects are related to their geographical sources and contribute to adaptation to the local habitat. The Colorado potato beetle (Leptinotarsa decemlineata) (CPB) is a potato pest that causes serious economic losses in Xinjiang Uygur Autonomous Region (XJ) and Heilongjiang Province (HL), China. The influence of microorganisms in the invasion and dispersal of CPB is unclear. We studied microbial communities of CPB collected from nine geographic sources in China using high throughput sequencing technology. Bacteroidetes, Firmicutes, and Proteobacteria were the most dominant phyla, Clostridia, Bacteroidetes, and γ-Proteobacteria were the most dominant classes, Enterobacterales, Lactobacillales, Clostridiales, and Bacteroidales were the most dominant orders, and Enterobacteriaceae, Streptococcidae, Verrucomicrobiaceae, and Rikenellaceae were the most dominant families. There were significant differences, among sources, in the relative abundance of taxa at the genus level. A total of 383 genera were identified, and the dominant bacteria at the genus level were compared between XJ and HL.Pseudomonaswas the unique dominant microorganism in the HL area, and the other four microorganisms (Lelliottia,Enterococcus,Enterobacter, andLactococcus) were common within the 2 regions. Bacterial community diversity in CPB from Urumqi, Jimunai, and Wenquan was higher than diversity in other regions. T-Distributed Stochastic Neighbor Embedding (tSNE) analysis indicated that order and genus were appropriate taxonomic levels to distinguish geographical sources of CPB. These findings provide insight into the diversity of microorganisms of CPB in the differences among geographically isolated populations.
Gut Microbial Composition and Diversity in Four Ophiuroid Species: Divergence Between Suspension Feeder and Scavenger and Their Symbiotic Microbes
Authors: Dong Yue , Li Yixuan , He Peiqing , Wang Zongling , Fan Shiliang , Zhang Zhixin , Zhang Xuelei , Xu Qinzeng
Published: March 2021

Gut microbiota have important roles in the survival and adaptation of the host. Ophiuroids, as the worldwide dominant benthos, have ecological roles in benthic–pelagic coupling in the sea floor. However, little is known about the composition and diversity of their gut microbiota and its potential functions in benthic ecosystems. In present study, we preformed 16S rRNA sequencing and function analysis in four dominant species (Stegophiura sladeni, Ophiopholis mirabilis, Ophiura sarsii vadicola, and Ophiura kinbergi) with two feeding types (suspension feeding/herbivores and scavenger/carnivores) from the Yellow Sea, China. Results showed that 56 phyla and 569 genera of microbiota were identified among ophiuroid guts. Multivariate and diversity analyses showed that the ophiuroid gut microbiota were independent and have higher biodiversity to the sediment microbial in the Yellow Sea. Phyla Proteobacteria, Firmicutes, Tenericutes, and Bacteroidetes were the dominant bacteria, with more than 80% abundance among the four ophiuroid species. A comparison among the gut microbial compositions among four ophiuroids showed the similarity of two offshore carnivore ophiuroids (S. sladeni and O. sarsii vadicola) and variation in the dominant microbiota types of three nearshore ophiuroids (S. sladeni, O. mirabilis, and O. kinbergi). The functional analysis revealed the significant differences of the environment-related expression in S. sladeni gut microbiota between nearshore and offshore environments. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional annotation showed the significant divergence of metabolism pathways between two nearshore species, the herbivores O. mirabilis and carnivores S. sladeni, such as the Lipid metabolism, Carbohydrate metabolism, and Metabolism of cofactors and vitamins. The homolog search and phylogenetic analysis identified the first gut symbiotic Candidatus Hepatoplasma in S. sladeni with important roles for the nutrient metabolisms. Overall, our study reported the comprehensive data of ophiuroid gut microbiota, while the functional microbiome provides insight into the physiology and environmental adaptation in ophiuroids.
Inactivation and Subsequent Growth Kinetics of Listeria monocytogenes After Various Mild Bactericidal Treatments
Authors: Fang Taisong , Wu Yufan , Xie Yani , Sun Linjun , Qin Xiaojie , Liu Yangtai , Li Hongmei , Dong Qingli , Wang Xiang
Published: March 2021

This study was carried out to investigate the effects of mild heat, lactic acid, benzalkonium chloride and nisin treatments on the inactivation, sublethal injury, and subsequent growth of Listeria monocytogenes. Results showed that the Bigelow model successfully described the thermal inactivation kinetics, while the Log-linear model with tail consistently offered the most accurate fit to LA, BC, and nisin inactivation curves of cells. Differential plating indicated that percentage of sublethal injury for nisin treated cells was significantly higher than that for the other three treatments. Compared to non-treated cells, significant extension of lag time was observed for all treated cells. The longer exposures to heat treatment contributed to the extended lag time of the survivors. While for LA, BC and nisin treated cells, the longest lag time was not observed at the most severe treatment conditions. The correlation analysis of sublethal injury percentage on the duration of lag time revealed that only heat treatment showed the significant correlation. Overall, the lag time analysis could evaluate a wide range of bacterial injury. Lag time of treated cells was significantly influenced by stress treatments and temperatures of recovery, however, there were not any significant changes in the maximum specific growth rate between treated and non-treated cells under isothermal recovery conditions. The information generated from this study is valuable for utilizing intervention strategies in the elimination or growth inhibition of L. monocytogenes.
Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition
Authors: Zhou Yilu , Hill Charlotte , Yao Liudi , Li Juanjuan , Hancock David , Downward Julian , Jones Mark G. , Davies Donna E. , Ewing Rob M. , Skipp Paul , Wang Yihua
Published: March 2021

Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in which signals transduced by RAS and transforming growth factor (TGF)-β play critical roles. To identify downstream molecular events following RAS and/or TGF-β activation, we performed proteomic analysis using a quantitative label-free approach (LC-HDMSE) to provide in-depth proteome coverage and estimates of protein concentration in absolute amounts. Data are available via ProteomeXchange with identifier PXD023720. We chose ATIIER:KRASV12as an experimental cell line in which RAS is activated by adding 4-hydroxytamoxifen (4-OHT). Proteomic analysis of ATII cells treated with 4-OHT or TGF-β demonstrated that RAS activation induces an epithelial–mesenchymal transition (EMT) signature. In contrast, under the same conditions, activation of TGF-β signaling alone only induces a partial EMT. EMT is a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties, and is involved in embryonic development, wound healing, fibrosis and cancer metastasis. Thus, these results could help to focus research on the identification of processes that are potentially driving EMT-related human disease.
The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency
Authors: Chen Xiaoyan , Wang Rong , Huang Xusheng , Yang Fei , Yu Shengyuan
Published: March 2021

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.

Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.

Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.

Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio <3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P < 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P < 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.

Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.
Distance Neurological Supervision Using Telestroke Does Not Increase Door-to-Needle Time in Acute Ischemic Stroke Management: The Experience of Two Regional Stroke Units
Authors: Sood Radhika , Annoni Jean-Marie , Humm Andrea M. , Accolla Ettore , Bill Olivier , Toledo Sotomayor Guillermo , Niederhauser Julien , Medlin Friedrich
Published: March 2021

Background and Aims: Timely administration of recombinant tissue plasminogen activator (r-tPA) improves clinical outcomes in acute ischemic stroke patients. This study aims to explore the influence of the systematic presence on site of a neurologist compared with telestroke management on door-to-needle time in acute ischemic stroke outside of working hours (OWH).

Methods: This retrospective cohort study included all r-tPA-treated patients in the emergency rooms of two Swiss stroke units, Nyon Hospital [Groupement Hospitalier de l'Ouest Lémanique (GHOL)] and Fribourg Hospital [Hôpital de Fribourg (HFR)], between February 2014 and September 2018. Door-to-needle time was analyzed for patients admitted during working hours (WH' weekdays 08:00–18:00) and OWH (weekdays 18:00–08:00, weekends, and public holidays). The latter was compared between centers; OWH, every patient was evaluated prior to thrombolysis by a neurologist on site in GHOL, while HFR adopted distance neurological supervision with teleradiology, performed by telephone evaluation of relevant clinical information with online real-time access to brain imaging.

Results: Data were analyzed for 157 patients in HFR and 101 patients in GHOL. No statistically significant differences in baseline characteristics were found for the 258 r-tPA-treated acute ischemic stroke patients, in terms of age, gender, cardiovascular risk factors (hypertension, diabetes, and atrial fibrillation), and pre-Modified Rankin Scale (pre-mRs) between centers, with the exception of smoking and anticoagulation status. Patients in HFR presented with more severe strokes {median National Institutes of Health Stroke Scale (NIHSS) [6 (SD 6.88) (GHOL), 8 (SD 6.98) (HFR), p = 0.005]}. No significant differences in baseline characteristics were found as per admission time independently of the center. Door-to-needle time was significantly longer in the HFR cohort when compared with GHOL, irrespective of admission time. Both centers demonstrated significantly longer median door-to-needle time OWH. However, analysis of the door-to-needle time differences between WH and OWH showed no significant interaction using robust ANCOVA WRS2 analysis (p = 0.952) and a Bayesian model (BF01 = 3.97).

Conclusions: On-site systematic evaluation by a neurologist did not appear to influence door-to-needle time OWH, suggesting distance supervision may be time-efficient in thrombolysis. This supports existing prospective studies in hyperacute telestroke management. The relevance lies in optimizing resource use considering the increasing demand for emergency neurological management.
Impaired Binaural Hearing in Adults: A Selected Review of the Literature
Authors: Gallun Frederick J.
Published: March 2021

Despite over 100 years of study, there are still many fundamental questions about binaural hearing that remain unanswered, including how impairments of binaural function are related to the mechanisms of binaural hearing. This review focuses on a number of studies that are fundamental to understanding what is known about the effects of peripheral hearing loss, aging, traumatic brain injury, strokes, brain tumors, and multiple sclerosis (MS) on binaural function. The literature reviewed makes clear that while each of these conditions has the potential to impair the binaural system, the specific abilities of a given patient cannot be known without performing multiple behavioral and/or neurophysiological measurements of binaural sensitivity. Future work in this area has the potential to bring awareness of binaural dysfunction to patients and clinicians as well as a deeper understanding of the mechanisms of binaural hearing, but it will require the integration of clinical research with animal and computational modeling approaches.
Silencing of HuR Inhibits Osteosarcoma Cell Epithelial-Mesenchymal Transition via AGO2 in Association With Long Non-Coding RNA XIST
Authors: Liu Yongming , Zhang Yuan , Zhang Jinxue , Ma Jingchang , Xu Xuexue , Wang Yuling , Zhou Ziqing , Jiang Dongxu , Shen Shen , Ding Yong , Zhou Yong , Zhuang Ran
Published: March 2021

Background

Osteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.

Methods

HuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.

Results

Knockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.

Conclusion

Our findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.
Autophagy and Cancer Dormancy
Authors: Akkoc Yunus , Peker Nesibe , Akcay Arzu , Gozuacik Devrim
Published: March 2021

Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called “dormancy” for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.
Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer
Authors: Jiménez-Salazar Javier E. , Damian-Ferrara Rebeca , Arteaga Marcela , Batina Nikola , Damián-Matsumura Pablo
Published: March 2021

Estrogens have been implicated in the etiology of breast cancer for a long time. It has been stated that long-term exposure to estrogens is associated with a higher incidence of breast cancer, since estradiol (E2) stimulates breast cell growth; however, its effect on DNA damage/repair is only starting to be investigated. Recent studies have documented that estrogens are able to modify the DNA damage response (DDR) and DNA repair mechanisms. On the other hand, it has been proposed that DDR machinery can be altered by estrogen signaling pathways, that can be related to cancer progression and chemoresistance. We have demonstrated that E2 promotes c-Src activation and breast cancer cell motility, through a non-genomic pathway. This review discusses scientific evidence supporting this non-genomic mechanism where estrogen modifies the DNA repair pathways, and its relationship to potential causes of chemoresistance.
CD169 Expression on Lymph Node Macrophages Predicts in Patients With Gastric Cancer
Authors: Kumamoto Keiichiro , Tasaki Takashi , Ohnishi Koji , Shibata Michihiko , Shimajiri Shohei , Harada Masaru , Komohara Yoshihiro , Nakayama Toshiyuki
Published: March 2021

The induction of an anti-cancer immune responses is potentially associated with the efficacy of anti-cancer therapy. Recent studies have indicated that sinus macrophages in regional lymph nodes are involved in anti-cancer immune responses in the cancer microenvironment. In the present study, we investigated the correlation between lymphocyte infiltration in cancer tissues and macrophage activation in regional lymph nodes. We retrospectively identified 294 patients with gastric cancer who underwent surgery from 2008 to 2012. Using immunohistochemistry, we evaluated CD169-expression on CD68-positive macrophages, and the density of CD8-postive lymphocytes in tumor microenvironment. We statistically examined the correlation between CD169 and CD8 expression, and performed Cox regression analysis of potential prognostic factors, including CD169 and CD8 expression, for cancer-specific survival (CSS) in patients with total and advanced gastric cancer. CD169 overexpression in lymph node sinus macrophages (LySMs) was positively correlated to the density of CD8-positive lymphocytes in primary cancer tissues (R = 0.367, p < 0.001). A high density of CD8-positive T lymphocytes in the primary site and a high level of CD169 expression in LySMs were independently associated with greater CSS in patients with total and advanced gastric cancer (p < 0.05 for all). The expression on CD169 in LySMs is a predictor of a favorable clinical course in patients with gastric cancer, and might be useful for evaluating anti-cancer immune responses.
Sensible Introduction of MR-Guided Radiotherapy: A Warm Plea for the RCT
Authors: Verkooijen Helena M. , Henke Lauren E.
Published: March 2021

Magnetic resonance guided radiotherapy (MRgRT) is the newest face of technology within a field long-characterized by continual technologic advance. MRgRT may offer improvement in the therapeutic index of radiation by offering novel planning types, like online adaptation, and improved image guidance, but there is a paucity of randomized data or ongoing randomized controlled trials (RCTs) to demonstrate clinical gains. Strong clinical evidence is needed to confirm the theoretical advantages of MRgRT and for the rapid dissemination of (and reimbursement for) appropriate use. Although some future evidence for MRgRT may come from large registries and non-randomized studies, RCTs should make up the core of this future data, and should be undertaken with thoughtful preconception, endpoints that incorporate patient-reported outcomes, and warm collaboration across existing MRgRT platforms. The advance and future success of MRgRT hinges on collaborative pursuit of the RCT.