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V A Anashkin, A A Baykov, R Lahti
Cystathionine β-synthase (CBS) domains discovered 20 years ago can bind different adenosine derivatives (AMP, ADP, ATP, S-adenosylmethionine, NAD, diadenosine polyphosphates) and thus regulate the activities of numerous proteins. Mutations in CBS domains of enzymes and membrane transporters are associated with several hereditary diseases. The regulatory unit is a quartet of CBS domains that belong to one or two polypeptides and usually form a conserved disk-like structure. CBS domains function as "internal inhibitors" in enzymes, and their bound ligands either amplify or attenuate the inhibitory effect...
October 2017: Biochemistry. Biokhimii︠a︡
Werner E G Müller, Shunfeng Wang, Maximilian Ackermann, Meik Neufurth, Renate Steffen, Egherta Mecja, Rafael Muñoz-Espí, Qingling Feng, Heinz C Schröder, Xiaohong Wang
Morbus Alzheimer neuropathology is characterized by an impaired energy homeostasis of brain tissue. We present an approach towards a potential therapy of Alzheimer disease based on the high-energy polymer inorganic polyphosphate (polyP), which physiologically occurs both in the extracellular and in the intracellular space. Rat pheochromocytoma (PC) 12 cells, as well as rat primary cortical neurons were exposed to the Alzheimer peptide Aβ25-35. They were incubated in vitro with polyphosphate (polyP); ortho-phosphate was used as a control...
October 16, 2017: International Journal of Molecular Sciences
Amber L Murch, Paul J Skipp, Peter L Roach, Petra C F Oyston
During conditions of nutrient limitation bacteria undergo a series of global gene expression changes to survive conditions of amino acid and fatty acid starvation. Rapid reallocation of cellular resources is brought about by gene expression changes coordinated by the signalling nucleotides' guanosine tetraphosphate or pentaphosphate, collectively termed (p)ppGpp and is known as the stringent response. The stringent response has been implicated in bacterial virulence, with elevated (p)ppGpp levels being associated with increased virulence gene expression...
October 16, 2017: Microbiology
Yuan Li, Shan Liu, Jun Zhu
Recombinant strains expressing enzymes for ATP regeneration and L-theanine production were constructed and used for the synthesis of L-theanine. The ppk gene encoding polyphosphate kinase (PPK) from Rhodobacter sphaeroides and gmas gene encoding γ-glutamylmethylamide synthetase (GMAS) from Methylovorus mays were synthesized, and two recombinant plasmids, pETDuet-ppk+gmas and pET21a-ppk+gmas were constructed for co-expression of PPK and GMAS in Escherichia coli BL21(DE3). SDS-PAGE analysis showed that PPK and GMAS were overexpressed in soluble form in both recombinant strains...
December 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Maximilian Ackermann, Xiaohong Wang, Shunfeng Wang, Meik Neufurth, Heinz C Schröder, Friedrich-Eckart Isemer, Werner E G Müller
Prostethic mesh material such as nonabsorbable polypropylene used in open and laparoscopic hernia repair are characterized by controllable mechanical properties but may elicit undesirable physiological reactions due to the nonphysiological inert polymer material. We succeeded in developing a biocompatible coating for these meshes, based on a physiological inorganic polymer, polyphosphate (polyP) that is morphogenetically active and used as a metabolic energy source, and a collagen matrix. The polyP/collagen hydrogel material was prepared by a freeze-extraction method, with amorphous Ca-polyP microparticles...
October 10, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Matthew Gumbleton, Raki Sudan, Sandra Fernandes, Robert W Engelman, Christopher M Russo, John D Chisholm, William G Kerr
The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells. However, unexpectedly, genetic ablation studies have shown that the effector functions of SHIP1-deficient NK and T cells are compromised in vivo...
October 10, 2017: Science Signaling
Yao Chen, Qiaofeng Yang, Sihong Sang, Zhaoyun Wei, Peng Wang
The plant hormone auxin controls many aspects of plant growth and development by promoting the degradation of Auxin/Indole-3-acetic acid (Aux/IAA) proteins. The domain II (DII) of Aux/IAA proteins is sufficient for eliciting the degradation by direct interacting with the auxin receptor F-box protein TIR1 to form a TIR1/AFBs-Aux/IAA complex in an auxin-dependent manner. However, the underlying mechanism of fine-tuning Aux/IAA degradation by auxin stimuli has remained to be elucidated. Here, we show that OsIPK2, a rice (Oryza sativa) inositol polyphosphate kinase, directly interacts with an Aux/IAA protein OsIAA11 to repress its degradation...
August 30, 2017: Plant & Cell Physiology
Curtis G Jones, Shannon M Pechauer, Brian R Curtis, Daniel W Bougie, Mehraboon S Irani, Binod Dhakal, Brenda Pierce, Richard H Aster, Anand Padmanabhan
Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin therapy. HIT diagnosis is established by recognizing thrombocytopenia and/or thrombosis in an affected patient and from the results of serological tests such as the platelet factor 4 (PF4)/heparin immunoassay (PF4 ELISA) and serotonin release assay (SRA). Recent studies suggest that HIT antibodies activate platelets by recognizing PF4 in a complex with platelet glycosaminoglycans (and/or polyphosphates) and that an assay based on this principle, the PF4-dependent P-selectin expression assay (PEA), may be even more accurate than the SRA for HIT diagnosis...
October 2017: Chest
Gregor Jereb, Borut Poljšak, Ivan Eržen
The cumulative phosphate intake in a typical daily diet is high and, according to several studies, already exceeds recommended values. The exposure of the general population to phosphorus via drinking water is generally not known. One of the hidden sources of phosphorus in a daily diet is sodium polyphosphate, commonly used as a drinking water softener. In Slovenia, softening of drinking water is carried out exclusively within the internal (household) drinking water supply systems to prevent the accumulation of limescale...
October 6, 2017: International Journal of Environmental Research and Public Health
Ji-Youn Sung, Kiyong Na, Hyun-Soo Kim
BACKGROUND/AIM: Aberrant expression of survival signaling pathways causes deregulation of cellular proliferation and resistance to apoptosis, and plays a crucial role in the development, progression and metastasis of cancer. Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and has a tumor-suppressive role in several human malignancies. MATERIALS AND METHODS: We analyzed the expression levels of INPP4B mRNA and protein in colorectal carcinoma (CRC) cell lines and tissue samples using western blot, quantitative real-time reverse-transcriptase polymerase chain reaction, and immunohistochemical staining...
October 2017: Anticancer Research
Cecilia Li, Sophie Lev, Desmarini Desmarini, Keren Kaufman-Francis, Adolfo Saiardi, Ana P G Silva, Joel P Mackay, Philip E Thompson, Tania C Sorrell, Julianne T Djordjevic
We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans. Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain. We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5...
October 4, 2017: Virulence
Jae-Eung Kim, Eui-Jin Kim, Hui Chen, Chang-Hao Wu, Michael W W Adams, Y-H Percival Zhang
Starch is a natural energy storage compound and is hypothesized to be a high-energy density chemical compound or solar fuel. In contrast to industrial hydrolysis of starch to glucose, an alternative ATP-free phosphorylation of starch was designed to generate cost-effective glucose 6-phosphate by using five thermophilic enzymes (i.e., isoamylase, alpha-glucan phosphorylase, 4-α-glucanotransferase, phosphoglucomutase, and polyphosphate glucokinase). This enzymatic phosphorolysis is energetically advantageous because the energy of α-1,4-glycosidic bonds among anhydroglucose units is conserved in the form of phosphorylated glucose...
September 30, 2017: Metabolic Engineering
Axel Schlagenhauf, Harald Haidl, Sina Pohl, Eva-Christine Weiss, Bettina Leschnik, Siegfried Gallistl, Wolfgang Muntean
Background: The neonatal hemostatic system exhibits a fragile balance featuring lower levels of clotting factors as well as inhibitors. Neonatal platelets show in-vitro hypoaggregability, but neonates exhibit well-functioning primary and secondary hemostasis despite this impairment. Recently, polyphosphate shed by activated platelets has been shown to induce a prothrombotic shift on the plasmatic coagulation system of adults. The impact of platelet derived polyphosphate might differ in neonates due to aforementioned peculiarities...
2017: Frontiers in Physiology
Catarina L Amorim, Marta Alves, Paula M L Castro, Isabel Henriques
Pharmaceuticals are micropollutants often present in wastewater treatment systems. In this study, the potential impact of such micropollutants on the bacterial population within aerobic granular sludge (AGS) bioreactor was investigated. The AGS bacterial community structure and composition were accessed combining DGGE fingerprinting and barcoded pyrosequencing analysis. Both revealed the existence of a dynamic bacterial community, independently of the pharmaceuticals presence. The AGS microbiome at both phylum and class levels varied over time and, after stopping pharmaceuticals feeding, the bacterial community did not return to its initial composition...
September 28, 2017: Ecotoxicology and Environmental Safety
Lysann Bender, Henri Weidmann, Stefan Rose-John, Thomas Renné, Andy T Long
Anaphylaxis is a life-threatening allergic reaction. It is triggered by the release of pro-inflammatory cytokines and mediators from mast cells and basophils in response to immunologic or non-immunologic mechanisms. Mediators that are released upon mast cell activation include the highly sulfated polysaccharide and inorganic polymer heparin and polyphosphate (polyP), respectively. Heparin and polyP supply a negative surface for factor XII (FXII) activation, a serine protease that drives contact system-mediated coagulation and inflammation...
2017: Frontiers in Immunology
Meik Neufurth, Xiaohong Wang, Shunfeng Wang, Renate Steffen, Maximilian Ackermann, Natalie D Haep, Heinz C Schröder, Werner E G Müller
Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca(2+) and the physiological inorganic polymer, polyphosphate (polyP). Those MP had been fortified by mixing with poly-ε-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100°C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 µm and a stacked architecture leaving ≈0...
September 28, 2017: Acta Biomaterialia
Adolfo Saiardi, Cristina Azevedo, Yann Desfougères, Paloma Portela-Torres, Miranda S C Wilson
Inositol polyphosphates are a diverse and multifaceted class of intracellular messengers omnipresent in eukaryotic cells. These water-soluble molecules regulate many aspects of fundamental cell physiology. Removing this metabolic pathway is deleterious: inositol phosphate kinase null mutations can result in lethality or substantial growth phenotypes. Inositol polyphosphate synthesis occurs through the actions of a set of kinases that phosphorylate phospholipase-generated IP3 to higher phosphorylated forms, such as the fully phosphorylated IP6 and the inositol pyrophosphates IP7 and IP8...
September 22, 2017: Advances in Biological Regulation
Antonio Gómez-Outes, Minerva García-Fuentes, Mª Luisa Suárez-Gea
In the last decade, several direct oral anticoagulants (DOAC) targeting thrombin (dabigatran) or activated factor X (FXa) (rivaroxaban, apixaban and edoxaban) have been marketed for a number of indications related to prophylaxis and treatment of thrombotic diseases. All these drugs are effective in preventing thrombosis, but are associated with an increased bleeding risk. Areas covered: This review includes a summary of new targets for anticoagulation (e.g.: FXIa, FXIIa, protein disulfide isomerase, polyphosphates, etc...
September 27, 2017: Expert Opinion on Drug Discovery
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
D V Abramochkin, K B Pustovit, V S Kuz'min
The modulatory influence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on the effect of intramural autonomic nerve stimulation in isolated rabbit sinoatrial node were examined. Electrical activity of the sinoatrial node was recorded intracellularly. Against the background of blockade of adrenergic effects with propranolol (3×10(-6) M) or in preparations isolated 2 h after injection of reserpine (2 mg/kg), nerve stimulation induced short-term membrane hyperpolarization and diminished the sinus node firing rate...
September 25, 2017: Bulletin of Experimental Biology and Medicine
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