53 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 2021/01/05

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.

Genetic analysis of freezing tolerance in camelina [Camelina sativa (L.) Crantz] by diallel cross of winter and spring biotypes.

Planta. 2021 Jan 02;253(1):9

Authors: Soorni J, Kazemitabar SK, Kahrizi D, Dehestani A, Bagheri N

Abstract
MAIN CONCLUSION: Camelina biotypes had different responses to freezing stress, which was mainly inherited by additive gene effects and can be reliably used in breeding programs and for a better understanding of freezing tolerance mechanisms in camelina plants. Camelina [Camelina sativa (L.) Crantz] is a frost-tolerant oilseed plant that is cultivated as an autumn crop in semi-arid regions. However, camelina establishment in these areas is limited by low temperatures in winter that results in decreased seed yield. In the present study, genetic basis of freezing tolerance (FT) in spring and winter biotypes of camelina was analyzed at seedling stage using a diallel cross experiment. The parents consisted of two winter doubled haploid (DH) lines with high (DH34 and DH31), two spring lines with medium (DH19 and DH26), and two spring lines with low FT (DH08 and DH91). For this purpose, the parents along with F1 entries were subjected to freezing stress and survival percentage, electrolyte leakage, and lethal temperature for 50% mortality (LT50) of the lines were measured. Results showed that although both additive and non-additive effects of the genes determine the FT, further analyses indicated that it was mainly controlled by the additive effects. Therefore, selection-based methods may be more efficient for improving FT in camelina genotypes. The results of specific combining ability (SCA) and heterosis analysis among various DH lines suggested that more tolerant cultivars of camelina could be developed by targeted crossings. When a tolerant winter line and a susceptible spring line were crossed, their progenies showed a higher FT compared with the progenies of a cross between two susceptible spring lines indicating FT is controlled by additive effects of the genes in camelina plants. These findings provided new insight into the genetic basis of freezing-related traits in camelina and could be used for more sophisticated breeding programs.

PMID: 33389162 [PubMed - as supplied by publisher]

Transcription factor Pit-1 affects transcriptional timing in the dual-promoter human prolactin gene.

Endocrinology. 2021 Jan 03;:

Authors: McNamara AV, Awais R, Momiji H, Dunham L, Featherstone K, Harper CV, Adamson AA, Semprini S, Jones NA, Spiller DG, Mullins JJ, Finkenstädt BF, Rand D, White MRH, Davis JRE

Abstract
Gene transcription occurs in short bursts interspersed with silent periods, and these kinetics can be altered by promoter structure. The effect of alternate promoter architecture on transcription bursting is not known. We studied the human prolactin (hPRL) gene that contains two promoters, a pituitary-specific promoter that requires the transcription factor Pit-1, and displays dramatic transcriptional bursting activity, and an alternate upstream promoter that is active in non-pituitary tissues. We studied large hPRL genomic fragments with luciferase reporters, and used bacterial artificial chromosome (BAC) recombineering to manipulate critical promoter regions. Stochastic switch mathematical modelling of single-cell time-lapse luminescence image data revealed that the Pit-1-dependent promoter showed longer, higher-amplitude transcriptional bursts. Knockdown studies confirmed that the presence of Pit-1 stabilised and prolonged periods of active transcription. Pit-1 therefore plays an active role in establishing the timing of transcription cycles, in addition to its cell-specific functions.

PMID: 33388754 [PubMed - as supplied by publisher]

Comparing COVID-19 vaccine allocation strategies in India: A mathematical modelling study.

Int J Infect Dis. 2020 Dec 31;:

Authors: Foy BH, Wahl B, Mehta K, Shet A, Menon GI, Britto C

Abstract
BACKGROUND: The development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions.
METHODS: We used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations.
RESULTS: Prioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination.
CONCLUSIONS: Our findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.

PMID: 33388436 [PubMed - as supplied by publisher]

Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Aβ deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer's disease.

Exp Neurol. 2020 Dec 31;:113590

Authors: Nakanishi K, Sakakima H, Norimatsu K, Otsuka S, Takada S, Tani A, Kikuchi K

Abstract
It is well known that physical exercise reduces the risk of Alzheimer's disease (AD) and age-related cognitive decline. However, its mechanisms are still not fully understood. This study aimed to investigate the effect of aging and rotarod exercise (Ex) on cognitive function and AD pathogenesis in the hippocampus using senescence-accelerated mice prone 8 (SAMP8). Cognitive functions clearly declined at 9-months of age. Amyloid-beta (Aβ) deposition, neuronal loss, and glia activation-induced neuroinflammation increased with aging. The rotarod Ex prevented the decline of cognitive functions corresponding to the suppression of Aβ deposition, neuroinflammation, neuronal loss, inducible nitric oxide synthase (NOS) activities, and neuronal NOS activities. In addition, the rotarod Ex suppressed proinflammatory M1 phenotype microglia and A1 phenotype astrocytes. Our findings suggest that low-intensity motor balance and coordination exercise prevented age-related cognitive decline in the early stage of AD progression, possibly through the suppression of hippocampal Aβ deposition, neuronal loss, oxidative stress, and neuroinflammation, including reduced M1 and A1 phenotypes microglia and astrocytes.

PMID: 33388314 [PubMed - as supplied by publisher]

Signaling Dynamics Regulating Crosstalks between T-Cell Activation and Immune Checkpoints.

Trends Cell Biol. 2020 Dec 30;:

Authors: Kreileder M, Barrett I, Bendtsen C, Brennan D, Kolch W

Abstract
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) have been hailed as major advances in cancer therapeutics; however, in many cancers response rates remain low. Extensive research efforts are underway to improve the efficacy of ICIs. The signaling pathways regulated by immune checkpoints (ICs) may be an important lever as they interfere with T-cell activation when activated by ICIs. Here, we review the current understanding of T-cell receptor signaling and their intersection with IC signaling pathways. As these signaling processes are highly dynamic and controlled by intricate spatiotemporal mechanisms, we focus on aspects of kinetic regulation that are modulated by ICs. Recent advances in computational modeling and experimental methods that can resolve spatiotemporal dynamics provide insights that reveal molecular mechanisms and new potential approaches for improving the design and application of ICIs.

PMID: 33388215 [PubMed - as supplied by publisher]

Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19.

Cell Host Microbe. 2020 Dec 26;:

Authors: Guo Q, Zhao Y, Li J, Liu J, Yang X, Guo X, Kuang M, Xia H, Zhang Z, Cao L, Luo Y, Bao L, Wang X, Wei X, Deng W, Wang N, Chen L, Chen J, Zhu H, Gao R, Qin C, Wang X, You F

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.

PMID: 33388094 [PubMed - as supplied by publisher]

Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis.

Gastroenterology. 2020 Dec 30;:

Authors: Kummen M, Thingholm LB, Rühlemann MC, Holm K, Hansen SH, Moitinho-Silva L, Liwinski T, Zenouzi R, Storm-Larsen C, Midttun Ø, McCann A, Ueland PM, Høivik ML, Vesterhus M, Trøseid M, Laudes M, Lieb W, Karlsen TH, Bang C, Schramm C, Franke A, Hov JR

Abstract
BACKGROUND AND AIMS: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in PSC compared to healthy controls (HCs) and inflammatory bowel disease (IBD).
METHODS: Fecal DNA from two cohorts (one Norwegian and one German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs and 93 IBD patients without PSC were subjected to metagenomic shotgun sequencing, generating 17 billion paired end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses.
RESULTS: PSC patients had fewer microbial genes compared to HC (P<.0001). Compared to HC, PSC patients showed enrichment and increased prevalence of Clostridium species, and a depletion of e.g., Eubacterium spp. and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched chain amino acid (BCAA) synthesis (Qfdr<.05). Targeted metabolomics of plasma from an independent set of PSC patients and controls found reduced concentrations of vitamin B6 and BCAAs in PSC (P<.0001), which strongly associated with reduced liver transplantation-free survival (log-rank P<.001). No taxonomic or functional differences were detected between PSC patients with and without IBD.
CONCLUSION: The gut microbiome of PSC patients exhibits large functional differences compared to HC, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.

PMID: 33387530 [PubMed - as supplied by publisher]

Reduced Serum Zinc Ion Concentration Is Associated with Coronary Heart Disease.

Biol Trace Elem Res. 2021 Jan 02;:

Authors: Meng H, Wang Y, Zhou F, Ruan J, Duan M, Wang X, Yu Q, Yang P, Chen W, Meng F

Abstract
Imbalances in trace element concentrations in the blood as a result of poor nutrition may affect the development of coronary heart disease. To study the relationship between zinc ion concentration in the peripheral blood and coronary heart disease, we performed multiple logistic regression and hierarchical analyses on blood measurements of 3541 patients. The experimental group comprised 1253 patients diagnosed with coronary heart disease, and the control group included 2288 healthy patients. The zinc ion concentrations were measured by a color rendering method, and the results were analyzed using SPSS software. Fifteen laboratory quality evaluation samples from the Clinical Laboratory Center of the Chinese Ministry of Health were selected for analysis. The mean values and average bias were calculated. The estimated qualified judgment standard was < 1/2 TEa (the allowable total error for zinc). A hierarchical analysis of risk factors, including smoking, age, sex, and menopause in women, was performed. The results revealed that non-smoking, aging (especially postmenopausal women), and low blood zinc concentrations were independent risk factors for the development of coronary heart disease (P ≤ 0.05, zinc ion concentration less than 13.82 ± 2.91). The findings strongly suggest that decreased zinc ion concentrations in the peripheral blood can be used as an independent risk factor for the prediction of coronary heart disease, especially in older patients, non-smokers, and women, in particular, postmenopausal women.

PMID: 33387273 [PubMed - as supplied by publisher]

Identifying new variation at the J locus, previously identified as e6, in long juvenile 'Paranagoiana' soybean.

Theor Appl Genet. 2021 Jan 02;:

Authors: Nissan N, Cober ER, Sadowski M, Charette M, Golshani A, Samanfar B

Abstract
KEY MESSAGE: A previously identified soybean maturity locus, E6, is discovered to be J, with the long juvenile allele in Paranagoiana now deemed j-x. Soybean grown at latitudes of ~20° or lower can produce lower grain yields due to the short days. This limitation can be overcome by using the long juvenile trait (LJ) which delays flowering under short day conditions. Two LJ loci have been mapped to the same location on Gm04, J and E6. The objective of this research was to investigate the e6 allele in 'Paranagoiana' and determine if E6 and J are the same locus or linked loci. KASP markers showed that e6 lines did not have the j-1 allele of LJ PI 159925. A population fixed for E1 but segregating for E6, with e6 introgressed from Paranagoiana, showed single gene control for flowering and maturity under short days. Sequencing Glyma.04G050200, the J gene, with long amplification Taq found that the e6 line 'Paranagoiana' contains a Ty1-copia retrotransposon of ~10,000 bp, inserted within exon 4. PCR amplification of the cDNA of Glyma.04G050200 also showed differences between the mRNA sequences (presence of insertion in j-x). Hence, we conclude that the loci E6 and J are one locus and deem this new variation found in Paranagoiana as j-x.

PMID: 33386860 [PubMed - as supplied by publisher]

A deep learning approach to evaluate the feasibility of enzymatic reactions generated by retrobiosynthesis.

Biotechnol J. 2021 Jan 02;:e2000605

Authors: Kim Y, Ryu JY, Kim HU, Jang WD, Lee SY

Abstract
Retrobiosynthesis allows the designing of novel biosynthetic pathways for the production of chemicals and materials through metabolic engineering but generates a large number of reactions beyond the experimental feasibility. Thus, an effective method that can reduce a large number of the initially predicted enzymatic reactions has been needed. Here, we present a deep learning-based reaction feasibility checker named DeepRFC to classify the feasibility of a given enzymatic reaction with high performance and speed. DeepRFC is designed to receive Simplified Molecular-Input Line-Entry System (SMILES) strings of a reactant pair, which is defined as a substrate and a product of a reaction, as an input, and evaluates whether the input reaction is feasible. A deep neural network is selected for DeepRFC as it leads to better classification performance than five other representative machine learning methods examined. For validation, the performance of DeepRFC is compared with another in-house reaction feasibility checker that uses the concept of reaction similarity. Finally, the use of DeepRFC is demonstrated for the retrobiosynthesis-based design of novel one-carbon assimilation pathways. DeepRFC will allow retrobiosynthesis to be more practical for metabolic engineering applications by efficiently screening a large number of retrobiosynthesis-derived enzymatic reactions. DeepRFC is freely available at https://bitbucket.org/kaistsystemsbiology/deeprfc. This article is protected by copyright. All rights reserved.

PMID: 33386776 [PubMed - as supplied by publisher]

Mutant P53 induces MELK expression by release of wild-type P53-dependent suppression of FOXM1.

NPJ Breast Cancer. 2020 Jan 03;6(1):2

Authors: Bollu LR, Shepherd J, Zhao D, Ma Y, Tahaney W, Speers C, Mazumdar A, Mills GB, Brown PH

Abstract
Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, and is associated with a poor prognosis due to frequent distant metastasis and lack of effective targeted therapies. Previously, we identified maternal embryonic leucine zipper kinase (MELK) to be highly expressed in TNBCs as compared with ER-positive breast cancers. Here we determined the molecular mechanism by which MELK is overexpressed in TNBCs. Analysis of publicly available data sets revealed that MELK mRNA is elevated in p53-mutant breast cancers. Consistent with this observation, MELK protein levels are higher in p53-mutant vs. p53 wild-type breast cancer cells. Furthermore, inactivation of wild-type p53, by loss or mutation of the p53 gene, increases MELK expression, whereas overexpression of wild-type p53 in p53-null cells reduces MELK promoter activity and MELK expression. We further analyzed MELK expression in breast cancer data sets and compared that with known wild-type p53 target genes. This analysis revealed that MELK expression strongly correlates with genes known to be suppressed by wild-type p53. Promoter deletion studies identified a p53-responsive region within the MELK promoter that did not map to the p53 consensus response elements, but to a region containing a FOXM1-binding site. Consistent with this result, knockdown of FOXM1 reduced MELK expression in p53-mutant TNBC cells and expression of wild-type p53 reduced FOXM1 expression. ChIP assays demonstrated that expression of wild-type p53 reduces binding of E2F1 (a critical transcription factor controlling FOXM1 expression) to the FOXM1 promoter, thereby, reducing FOXM1 expression. These results show that wild-type p53 suppresses FOXM1 expression, and thus MELK expression, through indirect mechanisms. Overall, these studies demonstrate that wild-type p53 represses MELK expression by inhibiting E2F1A-dependent transcription of FOXM1 and that mutation-driven loss of wild-type p53, which frequently occurs in TNBCs, induces MELK expression by suppressing FOXM1 expression and activity in p53-mutant breast cancers.

PMID: 33386390 [PubMed - as supplied by publisher]

22 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 2021/01/02

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.

26 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 2021/01/01

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.

23 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 2021/01/01

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.

40 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 2020/12/31

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 2020/12/31

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.

26 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 2020/12/30

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.

88 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 2020/12/29

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.

12 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 2020/12/29

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.