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      A microencapsulated feed additive containing organic acids and botanicals has a distinct effect on proliferative and metabolic related signaling in the jejunum and ileum of broiler chickens

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          Abstract

          Well designed and formulated natural feed additives have the potential to provide many of the growth promoting and disease mitigating characteristics of in-feed antibiotics, particularly feed additives that elicit their effects on targeted areas of the gut. Here, we describe the mechanism of action of a microencapsulated feed additive containing organic acids and botanicals (AviPlus ®P) on the jejunum and ileum of 15-day-old broiler-type chickens. Day-of-hatch chicks were provided ad libitum access to feed containing either 0 or 500 g/MT of the feed additive for the duration of the study. Fifteen days post-hatch, birds were humanely euthanized and necropsied. Jejunum and ileum tissue samples were collected and either flash frozen or stored in RNA-later as appropriate for downstream applications. Chicken-specific kinome peptide array analysis was conducted on the jejunum and ileum tissues, comparing the tissues from the treated birds to those from their respective controls. Detailed analysis of peptides representing individual kinase target sites revealed that in the ileum there was a broad increase in the signal transduction pathways centering on activation of HIF-1α, AMPK, mTOR, PI3K-Akt and NFκB. These signaling responses were largely decreased in the jejunum relative to control birds. Gene expression analysis agrees with the kinome data showing strong immune gene expression in the ileum and reduced expression in the jejunum. The microencapsulated blend of organic acids and botanicals elicit a more anti-inflammatory phenotype and reduced signaling in the jejunum while resulting in enhanced immunometabolic responses in the ileum.

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          Understanding the Warburg effect: the metabolic requirements of cell proliferation.

          In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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            The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets

            Abstract Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein–protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To achieve this, STRING collects and scores evidence from a number of sources: (i) automated text mining of the scientific literature, (ii) databases of interaction experiments and annotated complexes/pathways, (iii) computational interaction predictions from co-expression and from conserved genomic context and (iv) systematic transfers of interaction evidence from one organism to another. STRING aims for wide coverage; the upcoming version 11.5 of the resource will contain more than 14 000 organisms. In this update paper, we describe changes to the text-mining system, a new scoring-mode for physical interactions, as well as extensive user interface features for customizing, extending and sharing protein networks. In addition, we describe how to query STRING with genome-wide, experimental data, including the automated detection of enriched functionalities and potential biases in the user's query data. The STRING resource is available online, at https://string-db.org/.
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              KEGG: integrating viruses and cellular organisms

              Abstract KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                22 March 2023
                2023
                : 14
                : 1147483
                Affiliations
                [1] 1 Southern Plains Agricultural Research Center , Agricultural Research Service , United States Department of Agriculture , College Station, TX, United States
                [2] 2 Department of Animal and Food Sciences , University of Delaware , Newark, DE, United States
                [3] 3 DIMEVET , University of Bologna , Bologna, Italy
                [4] 4 Vetagro S.p.A , Reggio Emilia, Italy
                [5] 5 Vetagro Inc. , Chicago, IL, United States
                Author notes

                Edited by: Gale Strasburg, Michigan State University, United States

                Reviewed by: Giri Athrey, Texas A&M University, United States

                Jiahui Xu, University of California, Irvine, United States

                Eric Wong, Virginia Tech, United States

                *Correspondence: Christina L. Swaggerty, christi.swaggerty@ 123456usda.gov

                This article was submitted to Avian Physiology, a section of the journal Frontiers in Physiology

                Article
                1147483
                10.3389/fphys.2023.1147483
                10075360
                37035681
                83b93b4f-fa88-4f0d-aaf1-0741b6e71101
                Copyright © 2023 Johnson, Arsenault, Piva, Grilli and Swaggerty.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 January 2023
                : 10 March 2023
                Funding
                Funded by: VetAgro Sup , doi 10.13039/501100011073;
                Award ID: 58-3091-8-005
                Funded by: Agricultural Research Service , doi 10.13039/100007917;
                Award ID: 3091-32000-035-00D
                This research was supported, in part, by Vetagro ((CS) Agreement number 58-3091-8-005; https://www.vetagro.com) and the USDA/ARS (3091-32000-035-00D; https://www.ars.usda.gov/research/project/?accnNo=430283). There was no additional external funding received for this study. Vetagro provided support in the form of salaries for AP and EG, and supplied the AviPlus feed amendment, but did not have any additional role in data collection and analysis, decision to publish, or preparation of the manuscript. USDA/ARS provided support in the form of salary for CLS and CNJ but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                broiler chicken,antibiotic alternatives,botanicals (thymol and vanillin),essential oils,organic acids (citric and sorbic),immunometabolism,kinome,gut health

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