Swine Inflammation and Necrosis Syndrome Is Associated with Plasma Metabolites and Liver Transcriptome in Affected Piglets

Swine Inflammation and Necrosis Syndrome can lead to severe clinical signs, especially in tails, ears, teats, and claws in pigs. Clinical and histopathological findings in newborn piglets with intact epidermis indicate a primarily endogenous etiology, and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharide (LPS) are assumed to play a central role in the development of the syndrome. We hypothesized that swine inflammation and necrosis syndrome (SINS) is indirectly triggered by gut-derived MAMPs entering the circulatory system via the liver and thereby causing derangements on liver metabolism. To test this hypothesis, metabolomes, candidate genes of the liver and liver transcriptomes of 6 piglets with high-grade clinical signs of SINS (SINS high) were examined and compared with 6 piglets without significant signs of SINS (SINS low). Several hepatic pro-inflammatory genes and genes involved in stress response were induced in piglets of the SINS high group. The most striking finding from hepatic transcript profiling and bioinformatic enrichment was that the most enriched biological processes associated with the approximately 220 genes induced in the liver of the SINS high group were exclusively related to metabolic pathways, such as fatty acid metabolic process. Within the genes (≈390) repressed in the liver of the SINS high group, enriched pathways were ribosome biogenesis, RNA processing, RNA splicing, spliceosome, and RNA transport. The transcriptomic findings were supported by the results of the metabolome analyses. These results provide the first evidence for the induction of an inflammatory process in the liver of piglets suffering from SINS, accompanied by lipid metabolic derangement.

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Swine Inflammation and Necrosis Syndrome (SINS)

Animals ◽

10.3390/ani11061670 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1670

Author(s):

Gerald Reiner ◽

Josef Kuehling ◽

Frederik Loewenstein ◽

Mirjam Lechner ◽

Sabrina Becker

Keyword(s):

Scientific Evidence ◽

Age Groups ◽

Clinical Signs ◽

Well Being ◽

Defence Mechanisms ◽

Newborn Piglets ◽

High Prevalence ◽

Histopathological Studies ◽

Molecular Patterns ◽

Tail Damage

Tail biting is a prevalent and undesirable behaviour in pigs and a major source of significant reduction in well-being. However, focusing on biting considers only one part of the solution, because tail damage can be found with a high prevalence without any action by other pigs. The lesions are not limited to the tail but can also be found in the ears, heels, soles, claw coronary bands, teats, navel, vulva, and face. Environmental improvement alone often fails to overcome the problem. This review addresses a new inflammation and necrosis syndrome in swine (SINS). It shows the clinical signs and the frequencies of occurrence in different age groups. It compiles scientific evidence from clinical and histopathological studies in newborn piglets that argue for a primary endogenous aetiology of the disease. Bringing together the findings of a broad body of research, the possible mechanisms leading to the disease are identified and then discussed. This part will especially focus on microbe-associated molecular patterns in the circulation and their role in activating defence mechanisms and inflammation. Finally, the methods are identified to ameliorate the problem by optimizing husbandry and selecting a suitable breeding stock.

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Dietary microRNA—A Novel Functional Component of Food

Advances in Nutrition ◽

10.1093/advances/nmy127 ◽

2019 ◽

Vol 10 (4) ◽

pp. 711-721 ◽

Cited By ~ 8

Author(s):

Lin Zhang ◽

Ting Chen ◽

Yulong Yin ◽

Chen-Yu Zhang ◽

Yong-Liang Zhang

Keyword(s):

Gene Expression ◽

Small Rnas ◽

Biological Significance ◽

Circulatory System ◽

Physiological Effects ◽

Biological Processes ◽

Regulate Gene Expression ◽

Functional Component ◽

Health And Disease ◽

Regulate Gene

ABSTRACT MicroRNAs are a class of small RNAs that play essential roles in various biological processes by silencing genes. Evidence emerging in recent years suggests that microRNAs in food can be absorbed into the circulatory system and organs of humans and other animals, where they regulate gene expression and biological processes. These food-derived dietary microRNAs may serve as a novel functional component of food, a role that has been neglected to date. However, a significant amount of evidence challenges this new concept. The absorption, stability, and physiological effects of dietary microRNA in recipients, especially in mammals, are currently under heavy debate. In this review, we summarize our current understanding of the unique characteristics of dietary microRNAs and concerns about both the mechanistic and methodological basis for studying the biological significance of dietary microRNAs. Such efforts will benefit continuing investigations and offer new perspectives for the interpretation of the roles of dietary microRNA with respect to the health and disease of humans and animals.

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Serological Response to Pasteurella multocida NanH Sialidase in Persistently Colonized Rabbits

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.5.825-834.2004 ◽

2004 ◽

Vol 11 (5) ◽

pp. 825-834 ◽

Cited By ~ 6

Author(s):

Susan Sanchez ◽

Shaikh Mizan ◽

Charlotte Quist ◽

Patricia Schroder ◽

Michelle Juneau ◽

...

Keyword(s):

Pasteurella Multocida ◽

Respiratory Infections ◽

Clinical Signs ◽

Circulatory System ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Serological Response ◽

Igg Antibody ◽

Sialidase Activity ◽

Upper Respiratory

ABSTRACT Pasteurella multocida is a mucosal pathogen that colonizes the upper respiratory system of rabbits. Respiratory infections can result, but the bacteria can also invade the circulatory system, producing abscesses or septicemia. P. multocida produces extracellular sialidase activity, which is believed to augment colonization of the respiratory tract and the production of lesions in an active infection. Previously, it was demonstrated that some isolates of P. multocida contain two unique sialidase genes, nanH and nanB, that encode enzymes with different substrate specificities (S. Mizan, A. D. Henk, A. Stallings, M. Meier, J. J. Maurer, and M. D. Lee, J. Bacteriol. 182:6874-6883, 2000). We developed a recombinant antigen enzyme-linked immunosorbent assay (ELISA) based on the NanH sialidase of P. multocida and demonstrated that rabbits that were experimentally colonized with P. multocida produce detectable anti-NanH immunoglobulin M (IgM) and IgG in serum, although they demonstrated no clinical signs of pasteurellosis. In addition, clinically ill pet rabbits infected with P. multocida possessed IgM and/or IgG antibody against NanH. The NanH ELISA may be useful for the diagnosis of P. multocida infections in sick rabbits as well as for screening for carriers in research rabbit colonies.

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Functional Proteomic Analysis of Human Nucleolus

Molecular Biology of the Cell ◽

10.1091/mbc.e02-05-0271 ◽

2002 ◽

Vol 13 (11) ◽

pp. 4100-4109 ◽

Cited By ~ 316

Author(s):

Alexander Scherl ◽

Yohann Couté ◽

Catherine Déon ◽

Aleth Callé ◽

Karine Kindbeiter ◽

...

Keyword(s):

Proteomic Analysis ◽

Ribosome Biogenesis ◽

Molecular Mechanisms ◽

Convincing Evidence ◽

Biological Processes ◽

Functional Classification ◽

Control Of Gene Expression ◽

Nucleolar Proteins ◽

Nuclear Domain

The notion of a “plurifunctional” nucleolus is now well established. However, molecular mechanisms underlying the biological processes occurring within this nuclear domain remain only partially understood. As a first step in elucidating these mechanisms we have carried out a proteomic analysis to draw up a list of proteins present within nucleoli of HeLa cells. This analysis allowed the identification of 213 different nucleolar proteins. This catalog complements that of the 271 proteins obtained recently by others, giving a total of ∼350 different nucleolar proteins. Functional classification of these proteins allowed outlining several biological processes taking place within nucleoli. Bioinformatic analyses permitted the assignment of hypothetical functions for 43 proteins for which no functional information is available. Notably, a role in ribosome biogenesis was proposed for 31 proteins. More generally, this functional classification reinforces the plurifunctional nature of nucleoli and provides convincing evidence that nucleoli may play a central role in the control of gene expression. Finally, this analysis supports the recent demonstration of a coupling of transcription and translation in higher eukaryotes.

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Alteration of RNA Splicing by Small-Molecule Inhibitors of the Interaction between NHP2L1 and U4

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555217735035 ◽

2017 ◽

Vol 23 (2) ◽

pp. 164-173 ◽

Cited By ~ 2

Author(s):

Barthelemy Diouf ◽

Wenwei Lin ◽

Asli Goktug ◽

Christy R. R. Grace ◽

Michael Brett Waddell ◽

...

Keyword(s):

Small Molecules ◽

Rna Splicing ◽

High Throughput Screening ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Therapeutic Strategies ◽

Biological Processes ◽

Time Resolved Fluorescence ◽

Time Resolved ◽

U4 Rna

Splicing is an important eukaryotic mechanism for expanding the transcriptome and proteome, influencing a number of biological processes. Understanding its regulation and identifying small molecules that modulate this process remain a challenge. We developed an assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to detect the interaction between the protein NHP2L1 and U4 RNA, which are two key components of the spliceosome. We used this assay to identify small molecules that interfere with this interaction in a high-throughput screening (HTS) campaign. Topotecan and other camptothecin derivatives were among the top hits. We confirmed that topotecan disrupts the interaction between NHP2L1 and U4 by binding to U4 and inhibits RNA splicing. Our data reveal new functions of known drugs that could facilitate the development of therapeutic strategies to modify splicing and alter gene function.

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Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells

The Journal of Cell Biology ◽

10.1083/jcb.200601105 ◽

2006 ◽

Vol 173 (2) ◽

pp. 207-218 ◽

Cited By ~ 103

Author(s):

Xavier Darzacq ◽

Nupur Kittur ◽

Sujayita Roy ◽

Yaron Shav-Tal ◽

Robert H. Singer ◽

...

Keyword(s):

Rna Splicing ◽

Ribosome Biogenesis ◽

Core Protein ◽

Single Cells ◽

Telomere Maintenance ◽

Rna Transcription ◽

The Core ◽

Core Proteins ◽

Rna Accumulation

Mammalian H/ACA RNPs are essential for ribosome biogenesis, premessenger RNA splicing, and telomere maintenance. These RNPs consist of four core proteins and one RNA, but it is not known how they assemble. By interrogating the site of H/ACA RNA transcription, we dissected their biogenesis in single cells and delineated the role of the non-core protein NAF1 in the process. NAF1 and all of the core proteins except GAR1 are recruited to the site of transcription. NAF1 binds one of the core proteins, NAP57, and shuttles between nucleus and cytoplasm. Both proteins are essential for stable H/ACA RNA accumulation. NAF1 and GAR1 bind NAP57 competitively, suggesting a sequential interaction. Our analyses indicate that NAF1 binds NAP57 and escorts it to the nascent H/ACA RNA and that GAR1 then replaces NAF1 to yield mature H/ACA RNPs in Cajal bodies and nucleoli.

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Binding patterns of RNA-binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqab055 ◽

2021 ◽

Vol 3 (3) ◽

Author(s):

Masahiro Onoguchi ◽

Chao Zeng ◽

Ayako Matsumaru ◽

Michiaki Hamada

Keyword(s):

Rna Splicing ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Noncoding Rnas ◽

Biological Processes ◽

Rna Sequences ◽

Rna Elements ◽

Long Interspersed Element ◽

Functional Rna

Abstract Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.

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Biological Processes Highlighted in Saccharomyces cerevisiae during the Sparkling Wines Elaboration

Microorganisms ◽

10.3390/microorganisms8081216 ◽

2020 ◽

Vol 8 (8) ◽

pp. 1216

Author(s):

María del Carmen González-Jiménez ◽

Teresa García-Martínez ◽

Anna Puig-Pujol ◽

Fina Capdevila ◽

Jaime Moreno-García ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Ribosome Biogenesis ◽

Protein Identification ◽

Saccharomyces Genome Database ◽

Wine Industry ◽

Yeast Cells ◽

Chromosome Organization ◽

Sparkling Wine ◽

Biological Processes ◽

Genome Database

Sparkling wines elaboration has been studied by several research groups, but this is the first report on analysis of biological processes according to the Gene Ontology terms (GO terms) and related to proteins expressed by yeast cells during the second fermentation of sparkling wines. This work provides a comprehensive study of the most relevant biological processes in Saccharomyces cerevisiae P29, a sparkling wine strain, during the second fermentation under two conditions (without and with endogenous CO2 overpressure) in the middle and the end of second fermentation. Consequently, a proteomic analysis with the OFFGEL fractionator and protein identification with LTQ Orbitrap XL coupled to HPLC were performed. The classification of biological processes was carried out using the tools provided by the Saccharomyces Genome Database. Results indicate that a greater number of biological processes were identified under condition without CO2 overpressure and in the middle of the fermentation versus the end of the second fermentation. The biological processes highlighted under condition without CO2 overpressure in the middle of the fermentation were involved in the carbohydrate and lipid metabolic processes and catabolic and biosynthetic processes. However, under CO2 overpressure, specific protein expression in response to stress, transport, translation, and chromosome organization and specific processes were not found. At the end of fermentation, there were higher specific processes under condition without CO2 overpressure; most were related to cell division, growth, biosynthetic process, and gene transcription resulting in increased cell viability in this condition. Under CO2 overpressure condition, the most representative processes were related to translation as tRNA metabolic process, chromosome organization, mRNA processing, ribosome biogenesis, and ribonucleoprotein complex assembly, probably in response to the stress caused by the hard fermentation conditions. Therefore, a broader knowledge of the adaptation of the yeast, and its behavior under typical conditions to produce sparkling wine, might improve and favor the wine industry and the selection of yeast for obtaining a high-quality wine.

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ProMetheusDB: an in-depth analysis of the high-quality human methyl-proteome

10.1101/2021.09.20.461082 ◽

2021 ◽

Author(s):

Enrico Massignani ◽

Roberto Giambruno ◽

Marianna Maniaci ◽

Luciano Nicosia ◽

Avinash Yadav ◽

...

Keyword(s):

Histone Methylation ◽

Rna Splicing ◽

Biological Processes ◽

Response Signal ◽

Post Translational Modification ◽

High Confidence ◽

High Quality ◽

False Discovery ◽

Depth Analysis ◽

Made In

Protein Arginine (R) methylation is a post-translational modification involved in various biological processes, such as RNA splicing, DNA repair, immune response, signal transduction, and tumour development. Although several advancements were made in the study of this modification by mass spectrometry, researchers still face the problem of a high false discovery rate. We present a dataset of high-quality methylations obtained from several different heavy methyl SILAC (hmSILAC) experiments analysed with a machine learning-based tool doublets and show that this model allows for improved high-confidence identification of real methyl-peptides. Overall, our results are consistent with the notion that protein R methylation modulates protein:RNA interactions and suggest a role in rewiring protein:protein interactions, for which we provide experimental evidence for a representative case (i.e. NONO:PSPC1). Upon intersecting our R-methyl-sites dataset with a phosphosites dataset, we observed that R methylation correlates differently with S/T-Y phosphorylation in response to various stimuli. Finally, we explored the application of hmSILAC to identify unconventional methylated residues and successfully identified novel histone methylation marks on Serine 28 and Threonine 32 of H3.

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Ribosomal Protein Rpl22 Regulates Development and Transformation Via Altering RNA Processing

Blood ◽

10.1182/blood.v128.22.3878.3878 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3878-3878 ◽

Cited By ~ 1

Author(s):

Minshi Wang ◽

Zheng Ser ◽

Shuyun Rao ◽

Shawn Fahl ◽

Yong Zhang ◽

...

Keyword(s):

Alternative Splicing ◽

Rna Processing ◽

Rna Splicing ◽

Ribosome Biogenesis ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Read Depth ◽

Mrna Splicing ◽

Transformation Potential ◽

Morpholino Oligonucleotides

Abstract Although it has long been reported that mutations in ribosome proteins (RP) are associated with increased cancer risk in humans, the molecular basis why which RP mutations do so remains unclear. Nevertheless, the prevailing view is that RP mutations, such as Rps19, are thought to alter transformation potential through general impairment of ribosome biogenesis or function. Importantly, recent observations are beginning to challenge this notion as too simplistic. We have determined that the RP, Rpl22, is not essential for ribosome biogenesis or global protein synthesis; however, its inactivation impairs the development of normal T lymphocytes and increases their transformation potential. Indeed, RPL22 is inactivated in human T acute lymphoblastic leukemia (T-ALL) and this is associated with reduced survival. Moreover, Rpl22-deficiency accelerates development of leukemia in a myristylated Akt2 transgenic (MyrAkt2 Tg) mouse model of T-ALL. To gain insight into how Rpl22 inactivation facilitates development of leukemia, we are performing unbiased transcriptomic and proteomic analysis on Rpl22+/+ and Rpl22-/- thymic lymphomas arising in the MyrAkt2 Tg model, and in an Rpl22-/- lymphoma reconstituted with Rpl22. Interestingly, relatively few changes in mRNA transcript read depth were observed; however, substantial differences in the proteome were observed. Pathway analysis revealed that the loss of Rpl22 altered the expression of proteins regulating RNA-processing, in particular RNA-splicing. Interestingly, interrogation of the transrciptome data for alternative splicing revealed that alterations in exon usage. The ability of Rpl22 to influence splicing appears to be conserved across species as alternative splicing was also observed in zebrafish embryos in which Rpl22 was knocked down using morpholino oligonucleotides. Consequently, we hypothesize that Rpl22 regulates biological events through its ability of binding to RNA targets, and controlling the expression of their protein products at least in part through altering mRNA splicing. How Rpl22 changes mRNA splicing pattern is currently under investigation. Disclosures No relevant conflicts of interest to declare.

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