Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA

Circulating DNA in plasma consists of short DNA fragments. The biological processes generating such fragments are not well understood. DNASE1L3 is a secreted DNASE1-like nuclease capable of digesting DNA in chromatin, and its absence causes anti-DNA responses and autoimmunity in humans and mice. We found that the deletion of Dnase1l3 in mice resulted in aberrations in the fragmentation of plasma DNA. Such aberrations included an increase in short DNA molecules below 120 bp, which was positively correlated with anti-DNA antibody levels. We also observed an increase in long, multinucleosomal DNA molecules and decreased frequencies of the most common end motifs found in plasma DNA. These aberrations were independent of anti-DNA response, suggesting that they represented a primary effect of DNASE1L3 loss. Pregnant Dnase1l3−/− mice carrying Dnase1l3+/− fetuses showed a partial restoration of normal frequencies of plasma DNA end motifs, suggesting that DNASE1L3 from Dnase1l3-proficient fetuses could enter maternal systemic circulation and affect both fetal and maternal DNA fragmentation in a systemic as well as local manner. However, the observed shortening of circulating fetal DNA relative to maternal DNA was not affected by the deletion of Dnase1l3. Collectively, our findings demonstrate that DNASE1L3 plays a role in circulating plasma DNA homeostasis by enhancing fragmentation and influencing end-motif frequencies. These results support a distinct role of DNASE1L3 as a regulator of the physical form and availability of cell-free DNA and may have important implications for the mechanism whereby this enzyme prevents autoimmunity.

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Size Distributions of Maternal and Fetal DNA in Maternal Plasma

Clinical Chemistry ◽

10.1373/clinchem.2003.024893 ◽

2004 ◽

Vol 50 (1) ◽

pp. 88-92 ◽

Cited By ~ 364

Author(s):

K C Allen Chan ◽

Jun Zhang ◽

Angela B Y Hui ◽

Nathalie Wong ◽

Tze K Lau ◽

...

Keyword(s):

Pregnant Women ◽

Size Distribution ◽

Maternal Plasma ◽

Rapid Expansion ◽

Molecular Characteristics ◽

Dna Fragments ◽

Dna Molecules ◽

Plasma Dna ◽

Fetal Dna ◽

Noninvasive Prenatal Diagnosis

Abstract Background: The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive prenatal diagnosis. Despite the rapid expansion in clinical applications, the molecular characteristics of plasma DNA in pregnant women remain unclear. Methods: We investigated the size distribution of plasma DNA in 34 nonpregnant women and 31 pregnant women, using a panel of quantitative PCR assays with different amplicon sizes targeting the leptin gene. We also determined the size distribution of fetal DNA in maternal plasma by targeting the SRY gene. Results: The median percentages of plasma DNA with size >201 bp were 57% and 14% for pregnant and nonpregnant women, respectively (P <0.001, Mann–Whitney test). The median percentages of fetal-derived DNA with sizes >193 bp and >313 bp were 20% and 0%, respectively, in maternal plasma. Conclusion: Plasma DNA molecules are mainly short DNA fragments. The DNA fragments in the plasma of pregnant women are significantly longer than those in the plasma of nonpregnant women, and the maternal-derived DNA molecules are longer than the fetal-derived ones.

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Feeding behaviour and bioerosion: the ecological role of the rock-boring urchin, Echinometra mathaei (de Blainville, 1825), in Okinawa reef flat

AQUATIC SCIENCE & MANAGEMENT ◽

10.35800/jasm.1.1.2013.1976 ◽

2013 ◽

Vol 1 (1) ◽

pp. 10

Author(s):

Noar Muda Satyawan ◽

Shelly Tutupoho ◽

Yusli Wardiatno ◽

Makoto Tsuchiya

Keyword(s):

Feeding Behaviour ◽

Reef Flat ◽

Type A ◽

Gut Contents ◽

Biological Processes ◽

Type B ◽

Night Time ◽

Echinometra Mathaei ◽

Benthic Ecosystems

Erosion rate on corals due to activities of other biota is called bioerosion. The rock-boring urchin, Echinometra mathaei, when it is abundant, plays a significant role in benthic ecosystems, including biological processes like coral erosion. During feeding, E. mathaei erodes calcium carbonate besides grazing on algae living on coral, so it plays an important role in both organic and inorganic carbons in coral reefs. The urchin E. mathaei actively feeds during the night time (nocturnal grazer). Although in Okinawa four types (A-D) of the urchin exist, the research only focused on the types A and B. Type A of E. mathaei produced 0.44951 g feces per day on average while type B produced 0.38030 g feces per day. CaCO3 analysis in feces and gut contents showed bioerosion rate of E. mathaei type A was 0.64492 g/individu/day, and 0.54436 g/individu/day in type B. There were no significant differences in bioerosion impact of E. mathaei type A and B© Laju erosi pada karang yang disebabkan oleh biota, dikenal dengan bioerosi. Bulu babi jenis Echinometra mathaei, ketika melimpah, menjadi sangat berpengaruh terhadap ekosistem bentik termasuk proses biologi seperti erosi karang. Selama aktivitas makan, E. mathaei menggerus kalsium karbonat dalam proporsi yang besar di samping alga yang tumbuh menempel pada karang sehingga memiliki peran penting dalam siklus karbon organik dan anorganik di ekosistem terumbu karang. Bulu babi E. mathaei aktif mencari makan pada malam hari (nocturnal grazer). Meskipun di Okinanawa ada 4 tipe (A-D), pada eksperimen kali ini memfokuskan pada tipe A dan B saja. Tipe A E. mathaei rata-rata memproduksi 0,44951 g feses/hari dan tipe B memproduksi 0,38030 g feses/hari. Berdasarkan analisis CaCO3 yang dilakukan pada feses dan isi lambung, laju bioerosi yang disebabkan oleh E. mathaei tipe A sebesar 0,64492 g/individu/hari sedangkan tipe B sebesar 0,54436 g/individu/hari. Tidak terdapat perbedaan dampak bioerosi yang signifikan antara E. mathaei tipe A dan B©

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Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200902144348 ◽

2020 ◽

Vol 23 ◽

Author(s):

Xiao Zhou ◽

Xiao-Fei Zhang ◽

Dong-Yan Guo ◽

Yan-Jun Yang ◽

Lin Liu ◽

...

Keyword(s):

Febrile Seizures ◽

Network Pharmacology ◽

Biological Processes ◽

Active Compounds ◽

Potential Core ◽

R Language ◽

The Core ◽

Multiple Factors ◽

Therapeutic Mechanism

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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Emerging multifaceted roles of BAP1 complexes in biological processes

Cell Death Discovery ◽

10.1038/s41420-021-00406-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Aileen Patricia Szczepanski ◽

Lu Wang

Keyword(s):

Transcriptional Repression ◽

Target Genes ◽

Regulatory Mechanisms ◽

Biological Processes ◽

Multiprotein Complex ◽

Downstream Target ◽

Evolutionarily Conserved ◽

Complex Forms ◽

Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

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MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽

10.3390/cells9010113 ◽

2020 ◽

Vol 9 (1) ◽

pp. 113 ◽

Cited By ~ 3

Author(s):

Stephanie Maia Acuña ◽

Lucile Maria Floeter-Winter ◽

Sandra Marcia Muxel

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Small Rnas ◽

Immune Cell ◽

Fine Tuning ◽

Biological Processes ◽

Host Interactions ◽

The Past ◽

Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

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Streptococcus suis Induces Expression of Cyclooxygenase-2 in Porcine Lung Tissue

Microorganisms ◽

10.3390/microorganisms9020366 ◽

2021 ◽

Vol 9 (2) ◽

pp. 366

Author(s):

Muriel Dresen ◽

Josephine Schenk ◽

Yenehiwot Berhanu Weldearegay ◽

Désirée Vötsch ◽

Wolfgang Baumgärtner ◽

...

Keyword(s):

Lung Tissue ◽

Streptococcus Suis ◽

Cyclooxygenase 2 ◽

Economic Losses ◽

Biological Processes ◽

Alveolar Tissue ◽

Cox 2 ◽

Ciliated Epithelial Cells ◽

Immunohistological Analysis

Streptococcus suis is a common pathogen colonising the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like inflammation modulation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E2 (PGE2) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE2 levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE2 production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infections with S. suis.

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miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

Journal of Experimental Medicine ◽

10.1084/jem.20101823 ◽

2011 ◽

Vol 208 (6) ◽

pp. 1189-1201 ◽

Cited By ~ 528

Author(s):

Mark P. Boldin ◽

Konstantin D. Taganov ◽

Dinesh S. Rao ◽

Lili Yang ◽

Jimmy L. Zhao ◽

...

Keyword(s):

Molecular Mechanisms ◽

Immune Cell ◽

Myeloid Cell ◽

Genetically Engineered ◽

Biological Processes ◽

Targeted Deletion ◽

Genetically Engineered Mice ◽

Immune Defects ◽

Molecular Brake

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

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NADPH oxidase-derived ROS and the regulation of pulmonary vessel tone

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00780.2011 ◽

2012 ◽

Vol 302 (11) ◽

pp. H2166-H2177 ◽

Cited By ~ 48

Author(s):

G. Frazziano ◽

H. C. Champion ◽

P. J. Pagano

Keyword(s):

Oxygen Tension ◽

Vascular Tone ◽

Systemic Circulation ◽

Oxygen Species ◽

Partial Pressure Of Oxygen ◽

Low Oxygen ◽

Key Factors ◽

Pulmonary Vessel ◽

Major Emphasis

Pulmonary vessel constriction results from an imbalance between vasodilator and vasoconstrictor factors released by the endothelium including nitric oxide, endothelin, prostanoids, and reactive oxygen species (ROS). ROS, generated by a variety of enzymatic sources (such as mitochondria and NADPH oxidases, a.k.a. Nox), appear to play a pivotal role in vascular homeostasis, whereas elevated levels effect vascular disease. The pulmonary circulation is very sensitive to changes in the partial pressure of oxygen and differs from the systemic circulation in its response to this change. In fact, the pulmonary vessels contract in response to low oxygen tension, whereas systemic vessels dilate. Growing evidence suggests that ROS production and ROS-related pathways may be key factors that underlie this differential response to oxygen tension. A major emphasis of our laboratory is the role of Nox isozymes in cardiovascular disease. In this review, we will focus our attention on the role of Nox-derived ROS in the control of pulmonary vascular tone.

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The role of a chemical loop in removal of hazardous contaminants from coke oven wastewater during its treatment

Open Chemistry ◽

10.1515/chem-2019-0142 ◽

2019 ◽

Vol 17 (1) ◽

pp. 1288-1300

Author(s):

Anna Kwiecińska-Mydlak ◽

Marcin Sajdak ◽

Katarzyna Rychlewska ◽

Jan Figa

Keyword(s):

Chemical Treatment ◽

Treatment Process ◽

Oxygen Demand ◽

Coke Oven ◽

Main Role ◽

Biological Processes ◽

Coal Processing ◽

Wastewater Treatment Process ◽

Iron Based

AbstractCoke oven liquor is one of the most contaminated liquid streams generated by the coal processing industry, thus its proper treatment and utilization is crucial for sustainable and environmentally neutral plant operation. The conventional wastewater treatment process comprises of chemical and biological processes. Within the current research the detailed role of chemical treatment is described. Commercially available iron-based coagulants (PIX100, PIX100COP, PIX113, PIX116) were tested to understand their removal efficiency and impact on the stream parameters. The influence of iron dose in the range of 300-500 mgFe/L on the process performance was also examined.It was found that the main role of chemical treatment was to bind toxicants harmful to activated sludge microorganisms, i.e. free and complex cyanides and sulphides. Among the tested iron-based conventional coagulants ferrous salts were more efficient than ferric salts. It was also observed that efficiency of the process strongly depended on wastewater properties (especially in regard to pH, which should be in the range of 9-10) and the coagulant selection needed to be done individually for a given wastewater type. The removal rates of particular contaminants were diversified and for free cyanides, complex cyanides and sulphides they were in the range of 23-91%, -156-77% and -357-98%, respectively. The expected, simultaneous removal of chemical oxygen demand (COD) during the treatment was not observed and even the parameter value increased after the process due to probable formation of compounds less vulnerable to oxidation.

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