606 results match your criteria altered stoichiometry

Stepwise Reversion of Multiply Mutated Recombinant Antitrypsin Reveals a Selective Inhibitor of Coagulation Factor XIa as Active as the M358R Variant.

Front Cardiovasc Med 2021 19;8:647405. Epub 2021 Mar 19.

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Alpha-1 antitrypsin (AAT, also known as alpha-1 proteinase inhibitor or SERPINA1) is the most abundant member of the serpin superfamily found in human plasma. The naturally occurring variant AAT M358R, altered at the P1 position of the critical reactive center loop (RCL), is re-directed away from inhibition of AAT's chief natural target, neutrophil elastase, and toward accelerated inhibition of thrombin (FIIa), kallikrein (Kal), and other proteases such as factor XIa (FXIa). FXIa is an emerging target for the development of antithrombotic agents, since patients with FXI deficiency are protected from thromboembolic disease and do not exhibit a strong bleeding tendency. Read More

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Enzyme stoichiometry evidence revealed that five years nitrogen addition exacerbated the carbon and phosphorus limitation of soil microorganisms in a forest.

Ying Yong Sheng Tai Xue Bao 2021 Feb;32(2):521-528

School of Geographical Science, Fujian Normal University, Fuzhou 350007, China.

The activity and stoichiometry of soil extracellular enzyme can provide a good indication for changes in soil nutrient availability and microbial demands for nutrients. However, it remains unclear how would nitrogen (N) deposition affect nutrient limitation of microbes in subtropical forest soils. We conducted a 5 years N addition experiment in a subtropical forest. Read More

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February 2021

Phosphoproteomic Analysis as an Approach for Understanding Molecular Mechanisms of cAMP-Dependent Actions.

Mol Pharmacol 2021 May 11;99(5):342-357. Epub 2021 Feb 11.

Departments of Pharmacology and Medicine (J.A.B., M.G., M.S.-A., M.-C.B., S.-E.O.), and Division of Metabolism, Endocrinology and Nutrition (K.E.B.), University of Washington, Seattle, Washington.

In recent years, highly sensitive mass spectrometry-based phosphoproteomic analysis is beginning to be applied to identification of protein kinase substrates altered downstream of increased cAMP. Such studies identify a very large number of phosphorylation sites regulated in response to increased cAMP. Therefore, we now are tasked with the challenge of determining how many of these altered phosphorylation sites are relevant to regulation of function in the cell. Read More

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Mesoporous bioactive glass composition effects on degradation and bioactivity.

Bioact Mater 2021 Jul 21;6(7):1921-1931. Epub 2020 Dec 21.

Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands.

Mesoporous bioactive glasses (MBGs) are promising materials for regenerative medicine, due to their favorable properties including bioactivity and degradability. These key properties, but also their surface area, pore structure and pore volume are strongly dependent on synthesis parameters and glass stoichiometry. However, to date no systematic study on MBG properties covering a broad range of possible compositions exists. Read More

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The complexity of co-limitation: nutrigenomics reveal non-additive interactions of calcium and phosphorus on gene expression in .

Proc Biol Sci 2020 12 23;287(1941):20202302. Epub 2020 Dec 23.

Department of Biology, Trent University, Peterborough, Ontario, Canada.

Many lakes across Canada and northern Europe have experienced declines in ambient phosphorus (P) and calcium (Ca) supply for over 20 years. While these declines might create or exacerbate nutrient limitation in aquatic food webs, our ability to detect and quantify different types of nutrient stress on zooplankton remains rudimentary. Here, we used growth bioassay experiments and whole transcriptome RNAseq, collectively nutrigenomics, to examine the nutritional phenotypes produced by low supplies of P and Ca separately and together in the freshwater zooplankter . Read More

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December 2020

Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity.

J Biol Chem 2020 Dec 17. Epub 2020 Dec 17.

Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, Spain.

Acetylation is known to regulate the activity of cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme in gluconeogenesis, by promoting the reverse reaction of the enzyme (converting phosphoenolpyruvate to oxaloacetate). It is also known that the histone acetyltransferase p300 can induce PCK1 acetylation in cells, but whether that is a direct or indirect function was not known. Here we initially set out to determine whether p300 can acetylate directly PCK1 in vitro. Read More

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December 2020

Effects of GABA Receptor α3 Subunit Epilepsy Mutations on Inhibitory Synaptic Signaling.

Front Mol Neurosci 2020 20;13:602559. Epub 2020 Nov 20.

Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.

Missense mutations T166M, Q242L, T336M, and Y474C in the GABA receptor (GABAR) α3 subunit gene are associated with epileptic seizures, dysmorphic features, intellectual disability, and developmental delay. When incorporated into GABARs expressed in oocytes, all mutations are known to reduce GABA-evoked whole-cell currents. However, their impact on the properties of inhibitory synaptic currents (IPSCs) is unknown, largely because it is difficult to establish, much less control, the stoichiometry of GABAR expressed in native neuronal synapses. Read More

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November 2020

cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.

Nat Genet 2020 12 23;52(12):1364-1372. Epub 2020 Nov 23.

Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.

Inappropriate stimulation or defective negative regulation of the type I interferon response can lead to autoinflammation. In genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, we identified biallelic mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA-processing complex. Mutations were associated with the misprocessing of canonical histone transcripts and a disturbance of linker histone stoichiometry. Read More

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December 2020

Differential regulation of osteopontin and CD44 correlates with infertility status in PCOS patients.

J Mol Med (Berl) 2020 12 13;98(12):1713-1725. Epub 2020 Oct 13.

Reproductive Biology and Gynaecological Oncology Group, Institute for Life Science 2, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK.

Endometrial receptivity is mediated by adhesion molecules at the endometrium-trophoblast interface where osteopontin (OPN) and CD44 form a protein complex that plays an important role in embryo recognition. Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory polycystic ovarian syndrome (PCOS) patients in the proliferative and secretory phases of the natural menstrual cycle and in 12 infertile anovulatory PCOS patients. Endometrial biopsies and blood samples were evaluated for expression of OPN and CD44 using RT-PCR, immunohistochemistry and ELISA analysis to determine circulating levels of OPN, CD44, TNF-α, IFN-γ and OPN and CD44 levels in biopsy media. Read More

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December 2020

Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: Insights into biophysical and structural studies.

Mol Biochem Parasitol 2020 11 19;240:111319. Epub 2020 Sep 19.

Protein Structure-Function Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg 2050, South Africa. Electronic address:

Schistosoma japonicum glutathione transferase (Sj26GST), an enzyme central to detoxification of electrophilic compounds in the parasite, is upregulated in response to drug treatment. Therefore, Sj26GST may serve as a potential therapeutic target for the treatment of schistosomiasis. Herewith, we describe the structural basis of inhibition of Sj26GST by ellagic acid (EA). Read More

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November 2020

Soil C-N-P pools and stoichiometry as affected by intensive management of camellia oleifera plantations.

PLoS One 2020 4;15(9):e0238227. Epub 2020 Sep 4.

Jiangxi Provincial Key Laboratory of Silviculture, College of Forestry, Jiangxi Agricultural University, Nanchang, China.

Intensive management of C. oleifera has produced many pure C. oleifera plantations. Read More

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October 2020

Distinct roles of alternative oxidase pathway during the greening process of etiolated algae.

Sci China Life Sci 2020 Jul 23. Epub 2020 Jul 23.

College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518055, China.

The vital function of mitochondrial alternative oxidase (AOX) pathway in optimizing photosynthesis during plant de-etiolation has been well recognized. However, whether and how AOX impacts the chloroplast biogenesis in algal cells remains unclear. In the present study, the role of AOX in regulating the reassembly of chloroplast in algal cells was investigated by treating Auxenochlorella protothecoides with salicylhydroxamic acid (SHAM), the specific inhibitor to AOX, in the heterotrophy to autotrophy transition process. Read More

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Programmed Proteolysis of Chemotaxis Proteins in Sinorhizobium meliloti: Features in the C-Terminal Region Control McpU Degradation.

J Bacteriol 2020 08 10;202(17). Epub 2020 Aug 10.

Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA

Chemotaxis and motility are important traits that support bacterial survival in various ecological niches and in pathogenic and symbiotic host interaction. Chemotactic stimuli are sensed by chemoreceptors or ethyl-accepting hemotaxis roteins (MCPs), which direct the swimming behavior of the bacterial cell. In this study, we present evidence that the cellular abundance of chemoreceptors in the plant symbiont can be altered by the addition of several to as few as one amino acid residues and by including common epitope tags such as 3×FLAG and 6×His at their C termini. Read More

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-Glycans on EGF domain-specific -GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization.

J Biol Chem 2020 06 6;295(25):8560-8574. Epub 2020 May 6.

Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan

Epidermal growth factor (EGF) domain-specific -GlcNAc transferase (EOGT) is an endoplasmic reticulum (ER)-resident protein that modifies EGF repeats of Notch receptors and thereby regulates Delta-like ligand-mediated Notch signaling. Several mutations that may affect putative -glycosylation consensus sites are recorded in the cancer database, but the presence and function of -glycans in EOGT have not yet been characterized. Here, we identified -glycosylation sites in mouse EOGT and elucidated their molecular functions. Read More

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Nutrients and water availability constrain the seasonality of vegetation activity in a Mediterranean ecosystem.

Glob Chang Biol 2020 08 27;26(8):4379-4400. Epub 2020 May 27.

Department for Biogeochemical Integration, Max-Planck-Institute for Biogeochemistry, Jena, Germany.

Anthropogenic nitrogen (N) deposition and resulting differences in ecosystem N and phosphorus (P) ratios are expected to impact photosynthetic capacity, that is, maximum gross primary productivity (GPP ). However, the interplay between N and P availability with other critical resources on seasonal dynamics of ecosystem productivity remains largely unknown. In a Mediterranean tree-grass ecosystem, we established three landscape-level (24 ha) nutrient addition treatments: N addition (NT), N and P addition (NPT), and a control site (CT). Read More

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The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells.

Int J Mol Sci 2020 Apr 20;21(8). Epub 2020 Apr 20.

CNR Istituto di Cristallografia Sede Secondaria di Catania, Via Gaifami 18, 95126 Catania, Italy.

Copper plays an important role as a regulator in many pathologies involving the angiogenesis process. In cancerogenesis, tumor progression, and angiogenic diseases, copper homeostasis is altered. Although many details in the pathways involved are still unknown, some copper-specific ligands have been successfully used as therapeutic agents. Read More

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Effect of phosphorus efficiency on elemental stoichiometry of two shrubs.

Plant Biol (Stuttg) 2020 Jul 15;22(4):615-622. Epub 2020 Apr 15.

State Key Laboratory of Grassland Agro-ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, China.

Phosphorus (P) is an important nutrient that can restrict plant growth. However, the influence of P deficiency on elemental homeostasis and application of the growth rate hypothesis in higher plants remain to be assessed. Two shrubs, Zygophyllum xanthoxylum and Nitraria tangutorum, were used as experiment material and subjected to five P addition treatments: 0, 17. Read More

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Effects of seasonal and decadal warming on soil enzymatic activity in a P-deficient Mediterranean shrubland.

Glob Chang Biol 2020 06 23;26(6):3698-3714. Epub 2020 Apr 23.

CSIC, Global Ecology Unit CREAF-CSIC-UAB, Bellaterra, Spain.

Soil enzymes are central in the response of terrestrial ecosystems to climate change, and their study can be crucial for the models' implementation. We investigated for 1 year the effects of warming and seasonality on the potential activities of five soil extracellular enzymes and their relationships with soil moisture, phosphorus (P) concentration, and other soil parameters in a P-limited Mediterranean semiarid shrubland. The site was continuously subjected to warming since 1999, and we compared data from this study to analogous data from 2004. Read More

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Experimental N and P additions relieve stoichiometric constraints on organic matter flows through five stream food webs.

J Anim Ecol 2020 06 2;89(6):1468-1481. Epub 2020 Apr 2.

Warnell School of Forestry and Natural Resources, University of Georgia, Athens, GA, USA.

Human activities have dramatically altered global patterns of nitrogen (N) and phosphorus (P) availability. This pervasive nutrient pollution is changing basal resource quality in food webs, thereby affecting rates of biological productivity and the pathways of energy and material flow to higher trophic levels. Here, we investigate how the stoichiometric quality of basal resources modulates patterns of material flow through food webs by characterizing the effects of experimental N and P enrichment on the trophic basis of macroinvertebrate production and flows of dominant food resources to consumers in five detritus-based stream food webs. Read More

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N-Terminal Amino Acids Determine KLF4 Protein Stability in 2A Peptide-Linked Polycistronic Reprogramming Constructs.

Stem Cell Reports 2020 03 27;14(3):520-527. Epub 2020 Feb 27.

Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

A common strategy for multi-protein expression is to link genes by self-cleaving 2A peptide sequences. Yet, little is known how the 2A peptide-derived N-terminal proline or adjacent non-native residues introduced during cDNA cloning affects protein stoichiometry. Polycistronic reprogramming constructs with altered KLF4 protein stoichiometry can influence induced pluripotent stem cell (iPSC) generation. Read More

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Optimization of ATP Synthase c-Rings for Oxygenic Photosynthesis.

Front Plant Sci 2019 30;10:1778. Epub 2020 Jan 30.

Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI, United States.

The conversion of sunlight into useable cellular energy occurs the proton-coupled electron transfer reactions of photosynthesis. Light is absorbed by photosynthetic pigments and transferred to photochemical reaction centers to initiate electron and proton transfer reactions to store energy in a redox gradient and an electrochemical proton gradient (proton motive force, ), composed of a concentration gradient (ΔpH) and an electric field (Δ), which drives the synthesis of ATP through the thylakoid FF-ATP synthase. Although ATP synthase structure and function are conserved across biological kingdoms, the number of membrane-embedded ion-binding subunits varies between organisms, ranging from 8 to 17, theoretically altering the H/ATP ratio for different ATP synthase complexes, with profound implications for the bioenergetic processes of cellular metabolism. Read More

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January 2020

Using Collision Cross Section Distributions to Assess the Distribution of Collision Cross Section Values.

Anal Chem 2020 03 27;92(6):4340-4348. Epub 2020 Feb 27.

Michael Barber Centre for Collaborative Mass Spectrometry, Manchester Institute of Biotechnology and Photon Science Institute, University of Manchester, 131 Princess Street, Manchester, M1 7DN, U.K.

Careful transfer of ions into the gas-phase permits the measurement of protein structures, with ion mobility-mass spectrometry, which provides shape and stoichiometry information. Collision cross sections (CCS) can be obtained from measurements made of the ions mobility through a given gas, and such structural information once obtained should also permit interlaboratory comparisons. However, until recently, there was not a recommended standard form for the reporting of such measurements. Read More

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Effects of warming, climate extremes and phosphorus enrichment on the growth, sexual reproduction and propagule carbon and nitrogen stoichiometry of Potamogeton crispus L.

Environ Int 2020 04 7;137:105502. Epub 2020 Feb 7.

College of Fisheries, Huazhong Agricultural University, Hubei Provincial Engineering Laboratory for Pond Aquaculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China. Electronic address:

Contemporary evidence suggests that submerged macrophytes are experiencing a global decline due to the multiple compounding anthropogenic stressors impacting shallow lake ecosystems. Eutrophication and climate change are two main widespread, often co-occurring stressors, yet evidence concerning their interactive effects on aquatic plants remains partial and fragmented. Predicting the response of submerged aquatic vegetation to the combined effects of nutrient pollution and compound climate warming (mean + variability) is therefore crucial for the conservation and management of these valuable and vulnerable ecosystems. Read More

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The geography of grassland plant chemistry and productivity accounts for ant sodium and sugar usage.

Natalie A Clay

J Anim Ecol 2020 02;89(2):272-275

School of Biological Sciences, Louisiana Tech University, Ruston, LA, USA.

In Focus: Kaspari, M., Welti, E. A. Read More

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February 2020

Effects of pesticide exposure and predation risk on nutrient cycling and primary production.

Sci Total Environ 2020 Feb 2;705:135880. Epub 2019 Dec 2.

Evolutionary Stress Ecology and Ecotoxicology, University of Leuven, Charles Deberiotstraat 32, B-3000 Leuven, Belgium. Electronic address:

Understanding how pesticides and natural stressors shape ecosystem functions remains a major challenge. A largely overlooked way how stressors may affect nutrient cycling and primary production is through effects on body stoichiometry and the egestion of elements. We investigated how exposure to the pesticide chlorpyrifos and to predation risk, an abundant natural stressor in aquatic systems, altered the stoichiometry of the bodies and the egested faecal pellets of Enallagma cyathigerum damselfly larvae and how this further cascaded into effects on primary production (algae growth). Read More

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February 2020

Cl and H coupling properties and subcellular localizations of wildtype and disease-associated variants of the voltage-gated Cl/H exchanger ClC-5.

J Biol Chem 2020 02 18;295(6):1464-1473. Epub 2019 Dec 18.

Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; O'Brien Urology Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Department of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.

Dent disease 1 (DD1) is caused by mutations in the gene encoding a voltage-gated electrogenic nCl/H exchanger ClC-5. Using ion-selective microelectrodes and oocytes, here we studied Cl/H coupling properties of WT ClC-5 and four DD1-associated variants (S244L, R345W, Q629*, and T657S), along with trafficking and localization of ClC-5. WT ClC-5 had a 2Cl/H exchange ratio at a V of +40 mV with a [Cl] of 104 mm, but the transport direction did not reverse with a [Cl] of 5 mm, indicating that ClC-5-mediated exchange of two Cl out for one H in is not permissible. Read More

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February 2020

One Guest or Two? A Crystallographic and Solution Study of Guest Binding in a Cubic Coordination Cage.

Chemistry 2020 Mar 6;26(14):3054-3064. Epub 2020 Feb 6.

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

A crystallographic investigation of a series of host-guest complexes in which small-molecule organic guests occupy the central cavity of an approximately cubic M L coordination cage has revealed some unexpected behaviour. Whilst some guests form 1:1 H⋅G complexes as we have seen before, an extensive family of bicyclic guests-including some substituted coumarins and various saturated analogues-form 1:2 H⋅G complexes in the solid state, despite the fact that solution titrations are consistent with 1:1 complex formation, and the combined volume of the pair of guests significantly exceeds the Rebek 55±9 % packing for optimal guest binding, with packing coefficients of up to 87 %. Re-examination of solution titration data for guest binding in two cases showed that, although conventional fluorescence titrations are consistent with 1:1 binding model, alternative forms of analysis-Job plot and an NMR titration-at higher concentrations do provide evidence for 1:2 H⋅G complex formation. Read More

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Phase-Variable Glycosylation in Nontypeable .

J Proteome Res 2020 01 10;19(1):464-476. Epub 2019 Dec 10.

Nontypeable (NTHi) is a leading cause of respiratory tract infections worldwide and continues to be a global health burden. Adhesion and colonization of host cells are crucial steps in bacterial pathogenesis, and in many strains of NTHi, the interaction with the host is mediated by the high molecular weight adhesins HMW1A and HMW2A. These adhesins are -glycoproteins that are modified by cytoplasmic glycosyltransferases HMW1C and HMW2C. Read More

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January 2020

The Ion Channel Activator Mefenamic Acid Requires KCNE1 and Modulates Channel Gating in a Subunit-Dependent Manner.

Mol Pharmacol 2020 02 13;97(2):132-144. Epub 2019 Nov 13.

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

The pairing of KCNQ1 and KCNE1 subunits together mediates the cardiac slow delayed rectifier current ( ), which is partly responsible for cardiomyocyte repolarization and physiologic shortening of the cardiac action potential. Mefenamic acid, a nonsteroidal anti-inflammatory drug, has been identified as an activator. Here, we provide a biophysical and pharmacological characterization of mefenamic acid's effect on Using whole-cell patch clamp, we show that mefenamic acid enhances activity in both a dose- and stoichiometry-dependent fashion by changing the slowly activating and deactivating current into an almost linear current with instantaneous onset and slowed tail current decay, sensitive to the blocker (3R,4S)-(+)--[3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy) chroman-4-yl]--methylmethanesulfonamide (HMR1556). Read More

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February 2020

Simulated climate change decreases nutrient resorption from senescing leaves.

Glob Chang Biol 2020 03 10;26(3):1795-1807. Epub 2019 Dec 10.

Departamento de Conservación de Suelos y Agua, Centro de Edafología y Biología Aplicada del Segura - Consejo Superior de Investigaciones Científicas (CEBAS-CSIC), Murcia, Spain.

Nutrient resorption is the process whereby plants recover nutrients from senescing leaves and reallocate them to storage structures or newer tissues. Elemental resorption of foliar N and P has been shown to respond to temperature and precipitation, but we know remarkably little about the influence of warming and drought on the resorption of these and other essential plant macro- and micronutrients, which could alter the ability of species to recycle their nutrients. We conducted a 5 year manipulative field study to simulate predicted climate change conditions and studied the effects of warming (W), rainfall reduction (RR), and their combination (W+RR) on nutrient resorption efficiency in five coexisting shrub species in a semiarid shrubland. Read More

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