31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

58 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A Serum Protein Signature is associated with Rheumatoid Arthritis development.

Arthritis Rheumatol. 2020 Aug 07;:

Authors: O'Neil LJ, Spicer V, Smolik I, Meng X, Goel RR, Anaparti V, Wilkins J, El-Gabalawy HS

Abstract
OBJECTIVES: The pathophysiologic events that precede the onset of Rheumatoid Arthritis (RA) remain incompletely understood. We aimed to identify changes in the serum proteome that precede RA and provide new insights into the pathogenic mechanisms that lead to its development.
METHODS: We studied a cohort of first-degree relatives (FDR) of Indigenous North American RA patients using the SOMAscan platform and determined the levels of 1307 proteins in multiple longitudinal serum samples from seventeen individuals who were followed prospectively into disease onset. Proteomic signatures from this Progressor group were compared to those of At-risk ACPA positive (n=63) and ACPA negative (n=47) individuals. Machine learning was used to identify a protein signature that accurately classifies individuals at highest risk of future RA development.
RESULTS: We identified a pre-clinical proteomic signature that differentiates Progressors from At-risk individuals, irrespective of ACPA status (AUC=0.913, accuracy=91.2%). Importantly, the predictive pre-clinical proteomic signature was present not only in samples obtained close to the onset of RA, but also samples obtained a median of 30.9 months prior to onset. Network analysis implicated the activation of toll like receptor 2 (TLR2) and production of TNF and IL1 as key events that precede progression.
CONCLUSIONS: Alterations in the serum proteome in the pre-clinical phase of RA exist years prior to the onset of disease. Our findings suggest that the serum proteome provides a rich source of proteins that serves both to classify At-risk individuals and to identify molecular pathways involved in the development of clinically detectable RA.

PMID: 32770634 [PubMed - as supplied by publisher]

Unsupervised inference of protein fitness landscape from deep mutational scan.

Mol Biol Evol. 2020 Aug 08;:

Authors: Fernandez-de-Cossio-Diaz J, Uguzzoni G, Pagnani A

Abstract
The recent technological advances underlying the screening of large combinatorial libraries in high-throughput mutational scans, deepen our understanding of adaptive protein evolution and boost its applications in protein design. Nevertheless, the large number of possible genotypes requires suitable computational methods for data analysis, the prediction of mutational effects and the generation of optimized sequences. We describe a computational method that, trained on sequencing samples from multiple rounds of a screening experiment, provides a model of the genotype-fitness relationship. We tested the method on five large-scale mutational scans, yielding accurate predictions of the mutational effects on fitness. The inferred fitness landscape is robust to experimental and sampling noise and exhibits high generalization power in terms of broader sequence space exploration and higher fitness variant predictions. We investigate the role of epistasis and show that the inferred model provides structural information about the 3D contacts in the molecular fold.

PMID: 32770229 [PubMed - as supplied by publisher]

Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites.

Nat Commun. 2020 Aug 07;11(1):3940

Authors: Promonet A, Padioleau I, Liu Y, Sanz L, Biernacka A, Schmitz AL, Skrzypczak M, Sarrazin A, Mettling C, Rowicka M, Ginalski K, Chedin F, Chen CL, Lin YL, Pasero P

Abstract
R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops in the human genome, here, we map RNA:DNA hybrids, replication stress markers and DNA double-strand breaks (DSBs) in cells depleted for Topoisomerase I (Top1), an enzyme that relaxes DNA supercoiling and prevents R-loop formation. RNA:DNA hybrids are found at both promoters (TSS) and terminators (TTS) of highly expressed genes. In contrast, the phosphorylation of RPA by ATR is only detected at TTS, which are preferentially replicated in a head-on orientation relative to the direction of transcription. In Top1-depleted cells, DSBs also accumulate at TTS, leading to persistent checkpoint activation, spreading of γ-H2AX on chromatin and global replication fork slowdown. These data indicate that fork pausing at the TTS of highly expressed genes containing R-loops prevents head-on conflicts between replication and transcription and maintains genome integrity in a Top1-dependent manner.

PMID: 32769985 [PubMed - as supplied by publisher]

Pathogen-induced tissue-resident memory TH17 (TRM17) cells amplify autoimmune kidney disease.

Sci Immunol. 2020 Aug 07;5(50):

Authors: Krebs CF, Reimers D, Zhao Y, Paust HJ, Bartsch P, Nuñez S, Rosemblatt MV, Hellmig M, Kilian C, Borchers A, Enk LUB, Zinke M, Becker M, Schmid J, Klinge S, Wong MN, Puelles VG, Schmidt C, Bertram T, Stumpf N, Hoxha E, Meyer-Schwesinger C, Lindenmeyer MT, Cohen CD, Rink M, Kurts C, Franzenburg S, Koch-Nolte F, Turner JE, Riedel JH, Huber S, Gagliani N, Huber TB, Wiech T, Rohde H, Bono MR, Bonn S, Panzer U, Mittrücker HW

Abstract
Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.

PMID: 32769171 [PubMed - as supplied by publisher]

Evolutionary divergence reveals the molecular basis of EMRE dependence of the human MCU.

Life Sci Alliance. 2020 Oct;3(10):

Authors: MacEwen MJ, Markhard AL, Bozbeyoglu M, Bradford F, Goldberger O, Mootha VK, Sancak Y

Abstract
The mitochondrial calcium uniporter (MCU) is a calcium-activated calcium channel critical for signaling and bioenergetics. MCU, the pore-forming subunit of the uniporter, contains two transmembrane domains and is found in all major eukaryotic taxa. In amoeba and fungi, MCU homologs are sufficient to form a functional calcium channel, whereas human MCU exhibits a strict requirement for the metazoan protein essential MCU regulator (EMRE) for conductance. Here, we exploit this evolutionary divergence to decipher the molecular basis of human MCU's dependence on EMRE. By systematically generating chimeric proteins that consist of EMRE-independent Dictyostelium discoideum MCU and Homo sapiens MCU (HsMCU), we converged on a stretch of 10 amino acids in D. discoideum MCU that can be transplanted to HsMCU to render it EMRE independent. We call this region in human MCU the EMRE dependence domain (EDD). Crosslinking experiments show that EMRE directly interacts with HsMCU at its transmembrane domains as well as the EDD. Our results suggest that EMRE stabilizes the EDD of MCU, permitting both channel opening and calcium conductance, consistent with recently published structures of MCU-EMRE.

PMID: 32769116 [PubMed - as supplied by publisher]

Noncoding RNAs in peritoneal fibrosis: Background, Mechanism, and Therapeutic Approach.

Biomed Pharmacother. 2020 Jul 02;129:110385

Authors: Guo Y, Wang L, Gou R, Tang L, Liu P

Abstract
Peritoneal fibrosis (PF) is the main reason for patients to withdraw from peritoneal dialysis, while the mechanism underlying PF remains unclear. Increasing evidence has demonstrated the regulatory roles of different classes of noncoding RNAs (ncRNAs) in PF. MicroRNAs (miRNAs), which belong to a distinct class of ncRNAs, play crucial roles in the post-transcriptional regulation of gene expression. Studies have suggested that miRNAs play important roles in the pathogenesis of PF and have the potential to be used as diagnostic markers and therapeutic targets for PF in the future. Long noncoding RNAs (lncRNAs) have raised much attention in the recent years, which are involved in the pathophysiological processes of many diseases, including tumors, heart diseases and so on. Recently, some researchers have begun to notice the roles of lncRNAs in PF, and found that lncRNAs play certain roles in the pathogenesis of PF. Circular RNAs (circRNAs) have been proven to be participated in the pathogenesis of many diseases, including tumor metastasis, organ fibrosis and so on. However, studies on the correlation of circRNAs and PF are rather poor compared with miRNAs and lncRNAs. In this review, we will focus on the findings of ncRNAs in peritoneal dialysis therapy and discuss the rising interests in ncRNAs as diagnostic and therapeutic targets of PF.

PMID: 32768932 [PubMed - as supplied by publisher]

Dual-Color Single-Cell Imaging of the Suprachiasmatic Nucleus Reveals a Circadian Role in Network Synchrony.

Neuron. 2020 Aug 04;:

Authors: Shan Y, Abel JH, Li Y, Izumo M, Cox KH, Jeong B, Yoo SH, Olson DP, Doyle FJ, Takahashi JS

Abstract
The suprachiasmatic nucleus (SCN) acts as a master pacemaker driving circadian behavior and physiology. Although the SCN is small, it is composed of many cell types, making it difficult to study the roles of particular cells. Here we develop bioluminescent circadian reporter mice that are Cre dependent, allowing the circadian properties of genetically defined populations of cells to be studied in real time. Using a Color-Switch PER2::LUCIFERASE reporter that switches from red PER2::LUCIFERASE to green PER2::LUCIFERASE upon Cre recombination, we assess circadian rhythms in two of the major classes of peptidergic neurons in the SCN: AVP (arginine vasopressin) and VIP (vasoactive intestinal polypeptide). Surprisingly, we find that circadian function in AVP neurons, not VIP neurons, is essential for autonomous network synchrony of the SCN and stability of circadian rhythmicity.

PMID: 32768389 [PubMed - as supplied by publisher]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/08/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.