scholarly journals Intramolecular 13C/12C signals inform about carbon allocation in plant leaves

2021 ◽  
Author(s):  
Thomas Wieloch ◽  
Thomas David Sharkey ◽  
Roland Anton Werner ◽  
Juergen Schleucher
Keyword(s):  
Metabolic Networks ◽  
Carbon Allocation ◽  
Mevalonate Pathway ◽  
Signal Propagation ◽  
Dihydroxyacetone Phosphate ◽  
Carbon Uptake ◽  
Physiological Processes ◽  
Signal Environment ◽  
C3 Metabolism

- Stable isotopes at natural abundance are key tools to study physiological processes occurring outside the temporal scope of manipulation and monitoring experiments. Whole-molecule carbon isotope ratios (13C/12C) enable assessments of plant carbon uptake yet conceal information about carbon allocation. Here, we identify an intramolecular 13C/12C signal at tree-ring glucose C-5 and C-6, develop experimentally testable theories on its origin, and test these theories. - First, we assess the potential of processes within C3 metabolism for signal introduction based (inter alia) on constraints on signal propagation posed by metabolic networks. Second, we support our theoretical framework by re-analysing published 13C/12C data and modelling signal-environment relationships. - We propose the intramolecular signal reports carbon allocation into major metabolic pathways in actively photosynthesising leaf cells including the anaplerotic, shikimate, and non-mevalonate pathway. This is supported by previously reported whole-molecule 13C/12C increases in cellulose of ozone-treated Betula pendula and a highly significant relationship between the intramolecular signal and tropospheric ozone concentration. Additionally, we postulate a pronounced preference of leaf-cytosolic triose-phosphate isomerase to catalyse the forward reaction in vivo (dihydroxyacetone phosphate to glyceraldehyde 3-phosphate). - In conclusion, intramolecular 13C/12C analysis resolves information about carbon uptake and allocation enabling more comprehensive assessments of carbon metabolism than whole-molecule 13C/12C analysis.

Platelet Microtubules in Clot Structure Formation and Contractile Force Generation: Investigation of a Controversy

1986 ◽  
Vol 56 (01) ◽  
pp. 023-027 ◽  
Author(s):  
C J Jen ◽  
L V McIntire
Keyword(s):  
Network Formation ◽  
Contractile Force ◽  
Second Phase ◽  
Clot Retraction ◽  
Forming Process ◽  
Microtubule Organization ◽  
Physiological Processes ◽  
Fibrin Network ◽  
Two Parameters

SummaryWhether platelet microtubules are involved in clot retraction/ contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of micro tubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/ purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions. The latter is likely to be more analogous to physiological processes in vivo.

scholarly journals Non-invasive diagnostics in fossils - Magnetic Resonance Imaging of pathological belemnites

2005 ◽  
Vol 2 (2) ◽  
pp. 133-140 ◽  
Author(s):  
D. Mietchen ◽  
H. Keupp ◽  
B. Manz ◽  
F. Volke
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Soft Tissue ◽  
Clinical Diagnostics ◽  
Resonance Imaging ◽  
Non Invasive ◽  
Physiological Processes ◽  
Magnetic Resonance Imaging Mri ◽  
Invasive Diagnostics

Abstract. For more than a decade, Magnetic Resonance Imaging (MRI) has been routinely employed in clinical diagnostics because it allows non-invasive studies of anatomical structures and physiological processes in vivo and to differentiate between healthy and pathological states, particularly of soft tissue. Here, we demonstrate that MRI can likewise be applied to fossilized biological samples and help in elucidating paleopathological and paleoecological questions: Five anomalous guards of Jurassic and Cretaceous belemnites are presented along with putative paleopathological diagnoses directly derived from 3D MR images with microscopic resolution. Syn vivo deformities of both the mineralized internal rostrum and the surrounding former soft tissue can be traced back in part to traumatic events of predator-prey-interactions, and partly to parasitism. Besides, evidence is presented that the frequently observed anomalous apical collar might be indicative of an inflammatory disease. These findings highlight the potential of Magnetic Resonance techniques for further paleontological applications.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

DNA methylation in Yersinia enterocolitica: role of the DNA adenine methyltransferase in mismatch repair and regulation of virulence factors

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2291-2299 ◽  
Author(s):  
Stefan Fälker ◽  
M. Alexander Schmidt ◽  
Gerhard Heusipp
Keyword(s):  
Mismatch Repair ◽  
Yersinia Enterocolitica ◽  
Virulence Genes ◽  
Spontaneous Mutation ◽  
Gram Negative Bacteria ◽  
E Coli ◽  
Physiological Processes ◽  
Dna Adenine Methyltransferase

DNA adenine methyltransferase (Dam) plays an important role in physiological processes of Gram-negative bacteria such as mismatch repair and replication. In addition, Dam regulates the expression of virulence genes in various species. The authors cloned the dam gene of Yersinia enterocolitica and showed that Dam is essential for viability. Dam overproduction in Y. enterocolitica resulted in an increased frequency of spontaneous mutation and decreased resistance to 2-aminopurine; however, these effects were only marginal compared to the effect of overproduction of Escherichia coli-derived Dam in Y. enterocolitica, implying different roles or activities of Dam in mismatch repair of the two species. These differences in Dam function are not the cause for the essentiality of Dam in Y. enterocolitica, as Dam of E. coli can complement a dam defect in Y. enterocolitica. Instead, Dam seems to interfere with expression of essential genes. Furthermore, Dam mediates virulence of Y. enterocolitica. Dam overproduction results in increased tissue culture invasion of Y. enterocolitica, while the expression of specifically in vivo-expressed genes is not altered.

A reactive center loop–based prediction platform to enhance the design of therapeutic SERPINs

2021 ◽  
Vol 118 (45) ◽  
pp. e2108458118
Author(s):  
Wariya Sanrattana ◽  
Thibaud Sefiane ◽  
Simone Smits ◽  
Nadine D. van Kleef ◽  
Marcel H. Fens ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Serine Proteases ◽  
Protein C ◽  
Activated Protein C ◽  
Reactive Center Loop ◽  
Physiological Processes ◽  
Naturally Occurring ◽  
Reactive Center ◽  
Insight Into

Serine proteases are essential for many physiological processes and require tight regulation by serine protease inhibitors (SERPINs). A disturbed SERPIN–protease balance may result in disease. The reactive center loop (RCL) contains an enzymatic cleavage site between the P1 through P1’ residues that controls SERPIN specificity. This RCL can be modified to improve SERPIN function; however, a lack of insight into sequence–function relationships limits SERPIN development. This is complicated by more than 25 billion mutants needed to screen the entire P4 to P4’ region. Here, we developed a platform to predict the effects of RCL mutagenesis by using α1-antitrypsin as a model SERPIN. We generated variants for each of the residues in P4 to P4’ region, mutating them into each of the 20 naturally occurring amino acids. Subsequently, we profiled the reactivity of the resulting 160 variants against seven proteases involved in coagulation. These profiles formed the basis of an in silico prediction platform for SERPIN inhibitory behavior with combined P4 to P4’ RCL mutations, which were validated experimentally. This prediction platform accurately predicted SERPIN behavior against five out of the seven screened proteases, one of which was activated protein C (APC). Using these findings, a next-generation APC-inhibiting α1-antitrypsin variant was designed (KMPR/RIRA; / indicates the cleavage site). This variant attenuates blood loss in an in vivo hemophilia A model at a lower dosage than the previously developed variant AIKR/KIPP because of improved potency and specificity. We propose that this SERPIN-based RCL mutagenesis approach improves our understanding of SERPIN behavior and will facilitate the design of therapeutic SERPINs.

Food supplement “carrageenan” and its effect on the organism

2020 ◽  
Author(s):  
O.E. Luneva ◽  
Keyword(s):  
Gastrointestinal Tract ◽  
Food Additives ◽  
Food Supplement ◽  
The Body ◽  
Laboratory Rats ◽  
Experimental Part ◽  
In Vivo Experiments ◽  
Physiological Processes

Food additives are positioned as harmless, although, their components affectthe physiological processes associated with the permeability of the wall of the gastrointestinal tract (GIT) and intestinal microbiota. This article describes thecarrageenan supplement and its effects on the body in in vitro and in vivo experiments. The experimental part is devoted to analysis of the intestinalmicrobiota of laboratory rats with the consumption of the carrageenan dietary supplement in the amount of about 4,4 % of the standard feed.

scholarly journals In Vitro and in Vivo Imaging of Nitroxyl with Copper Fluorescent Probe in Living Cells and Zebrafish

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2551 ◽  
Author(s):  
Sathyadevi Palanisamy ◽  
Yu-Liang Wang ◽  
Yu-Jen Chen ◽  
Chiao-Yun Chen ◽  
Fu-Te Tsai ◽  
...  
Keyword(s):  
Critical Role ◽  
Model Organism ◽  
Living Cells ◽  
Biological Species ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Collective Data ◽  
Angeli's Salt

Nitroxyl (HNO) plays a critical role in many physiological processes which includes vasorelaxation in heart failure, neuroregulation, and myocardial contractility. Powerful imaging tools are required to obtain information for understanding the mechanisms involved in these in vivo processes. In order to develop a rapid and high sensitive probe for HNO detection in living cells and the zebrafish model organism, 2-((2-(benzothiazole-2yl)benzylidene) amino)benzoic acid (AbTCA) as a ligand, and its corresponding copper(II) complex Cu(II)-AbTCA were synthesized. The reaction results of Cu(II)-AbTCA with Angeli’s salt showed that Cu(II)-AbTCA could detect HNO quantitatively in a range of 40–360 µM with a detection limit of 9.05 µM. Furthermore, Cu(II)-AbTCA is more selective towards HNO over other biological species including thiols, reactive nitrogen, and reactive oxygen species. Importantly, Cu(II)-AbTCA was successfully applied to detect HNO in living cells and zebrafish. The collective data reveals that Cu(II)-AbTCA could be used as a potential probe for HNO detection in living systems.

scholarly journals Physiological Implications of Hydrogen Sulfide in Plants: Pleasant Exploration behind Its Unpleasant Odour

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Zhuping Jin ◽  
Yanxi Pei
Keyword(s):  
Hydrogen Sulfide ◽  
Growth And Development ◽  
Defense Responses ◽  
Plant Responses ◽  
Plant Growth And Development ◽  
Systematic Classification ◽  
Physiological Processes ◽  
Overwhelming Evidence

Recently, overwhelming evidence has proven that hydrogen sulfide (H2S), which was identified as a gasotransmitter in animals, plays important roles in diverse physiological processes in plants as well. With the discovery and systematic classification of the enzymes producing H2Sin vivo, a better understanding of the mechanisms by which H2S influences plant responses to various stimuli was reached. There are many functions of H2S, including the modulation of defense responses and plant growth and development, as well as the regulation of senescence and maturation. Additionally, mounting evidence indicates that H2S signaling interacts with plant hormones, hydrogen peroxide, nitric oxide, carbon monoxide, and other molecules in signaling pathways.

scholarly journals Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer

2021 ◽  
Author(s):  
Caterina Bartolacci ◽  
Cristina Andreani ◽  
Goncalo Dias do Vale ◽  
Stefano Berto ◽  
Margherita Melegari ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Fatty Acid ◽  
Metabolic Networks ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Genetically Engineered ◽  
De Novo Lipogenesis ◽  
Main Process

Mutant KRAS (KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role in tumorigenesis is still not sufficiently characterized to be exploited in cancer therapy. To identify metabolic networks specifically deregulated in KMLC, we characterized the lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that KMLC, but not EGFR-mutant (EGFR-MUT) LC, is enriched in triacylglycerides (TAG) and phosphatidylcholines (PC). We also found that KM upregulates fatty acid synthase (FASN), a rate-limiting enzyme in fatty acid (FA) synthesis promoting the synthesis of palmitate and PC. We determined that FASN is specifically required for the viability of KMLC, but not of LC harboring EGFR-MUT or wild type KRAS. Functional experiments revealed that FASN inhibition leads to ferroptosis, a reactive oxygen species (ROS)-and iron-dependent cell death. Consistently, lipidomic analysis demonstrated that FASN inhibition in KMLC leads to accumulation of PC with polyunsaturated FA (PUFA) chains, which are the substrate of ferroptosis. Integrating lipidomic, transcriptome and functional analyses, we demonstrated that FASN provides saturated (SFA) and monounsaturated FA (MUFA) that feed the Lands cycle, the main process remodeling oxidized phospholipids (PL), such as PC. Accordingly, either inhibition of FASN or suppression of the Lands cycle enzymes PLA2 and LPCAT3, promotes the intracellular accumulation of lipid peroxides and ferroptosis in KMLC both in vitro and in vivo. Our work supports a model whereby the high oxidative stress caused by KM dictates a dependency on newly synthesized FA to repair oxidated phospholipids, establishing a targetable vulnerability. These results connect KM oncogenic signaling, FASN induction and ferroptosis, indicating that FASN inhibitors already in clinical trial in KMLC patients (NCT03808558) may be rapidly deployed as therapy for KMLC.

scholarly journals Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Modar Kassan ◽  
Ajit Vikram ◽  
Young-Rae Kim ◽  
Qiuxia Li ◽  
Adam Kassan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Endothelial Function ◽  
Er Stress ◽  
High Fat Diet ◽  
Important Determinant ◽  
Class Iii ◽  
Caveolin 1 ◽  
Physiological Processes

Abstract Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress.

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