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1,159 results on '"Phosphorus-Oxygen Lyases"'

1. Reciprocal c-di-GMP signaling: Incomplete flagellum biogenesis triggers c-di-GMP signaling pathways that promote biofilm formation.

Author

Wu, Daniel, Zamorano-Sánchez, David, Pagliai, Fernando, Park, Jin, Floyd, Kyle, Lee, Calvin, Kitts, Giordan, Rose, Christopher, Bilotta, Eric, Wong, Gerard, and Yildiz, Fitnat

Subjects
Bacterial Proteins, Biofilms, Cyclic GMP, Escherichia coli Proteins, Fimbriae, Bacterial, Flagella, Gene Expression Regulation, Bacterial, Phosphorus-Oxygen Lyases, Second Messenger Systems, Signal Transduction, Vibrio cholerae
Abstract

The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also results in reduction of mannose-sensitive hemagglutinin (MSHA) pilus levels on the cell surface, suggesting interconnectivity of signal transduction pathways involved in biofilm formation. Strains lacking flagellar rotor components similarly launched an FDBR response, however this was independent of the status of assembly of the flagellar stator. We found that the FDBR response requires at least three specific diguanylate cyclases that contribute to increased c-di-GMP levels, and propose that activation of biofilm formation during this response relies on c-di-GMP-dependent activation of positive regulators of biofilm production. Together our results dissect how flagellum assembly activates c-di-GMP signaling circuits, and how V. cholerae utilizes these signals to transition from a motile to a sessile state.

Published
2020

2. Functional Specialization in Vibrio cholerae Diguanylate Cyclases: Distinct Modes of Motility Suppression and c-di-GMP Production.

Author

Zamorano-Sánchez, David, Xian, Wujing, Lee, Calvin, Salinas, Mauro, Thongsomboon, Wiriya, Cegelski, Lynette, Wong, Gerard, and Yildiz, Fitnat

Subjects
Vibrio cholerae, biofilm, c-di-GMP, motility, Biofilms, Cyclic GMP, Escherichia coli Proteins, Gene Deletion, Gene Expression Regulation, Bacterial, Locomotion, Phosphorus-Oxygen Lyases, Vibrio cholerae
Abstract

Vibrio cholerae biofilm formation and associated motility suppression are correlated with increased concentrations of cyclic diguanylate monophosphate (c-di-GMP), which are in turn driven by increased levels and/or activity of diguanylate cyclases (DGCs). To further our understanding of how c-di-GMP modulators in V. cholerae individually and collectively influence motility with cellular resolution, we determined how DGCs CdgD and CdgH impact intracellular c-di-GMP levels, motility, and biofilm formation. Our results indicated that CdgH strongly influences swim speed distributions; cells in which cdgH was deleted had higher average swim speeds than wild-type cells. Furthermore, our results suggest that CdgD, rather than CdgH, is the dominant DGC responsible for postattachment c-di-GMP production in biofilms. Lipopolysaccharide (LPS) biosynthesis genes were found to be extragenic bypass suppressors of the motility phenotypes of strains ΔcdgD and ΔcdgH We compared the motility regulation mechanism of the DGCs with that of Gmd, an LPS O-antigen biosynthesis protein, and discovered that comodulation of c-di-GMP levels by these motility effectors can be positively or negatively cooperative rather than simply additive. Taken together, these results suggest that different environmental and metabolic inputs orchestrate DGC responses of V. cholerae via c-di-GMP production and motility modulation.IMPORTANCE Cyclic diguanylate monophosphate (c-di-GMP) is a broadly conserved bacterial signaling molecule that affects motility, biofilm formation, and virulence. Although it has been known that high intracellular concentrations of c-di-GMP correlate with motility suppression and biofilm formation, how the 53 predicted c-di-GMP modulators in Vibrio cholerae collectively influence motility is not understood in detail. Here we used a combination of plate assays and single-cell tracking methods to correlate motility and biofilm formation outcomes with specific enzymes involved in c-di-GMP synthesis in Vibrio cholerae, the causative agent of the disease cholera.

Published
2019

3. High-throughput interaction screens illuminate the role of c-di-AMP in cyanobacterial nighttime survival.

Author

Rubin, Benjamin E, Huynh, TuAnh Ngoc, Welkie, David G, Diamond, Spencer, Simkovsky, Ryan, Pierce, Emily C, Taton, Arnaud, Lowe, Laura C, Lee, Jenny J, Rifkin, Scott A, Woodward, Joshua J, and Golden, Susan S

Subjects
Synechococcus, Phosphorus-Oxygen Lyases, Bacterial Proteins, Cyclic AMP, Proteomics, Signal Transduction, Oxidative Stress, Mutation, High-Throughput Screening Assays, Biotechnology, Genetics, Developmental Biology
Abstract

The broadly conserved signaling nucleotide cyclic di-adenosine monophosphate (c-di-AMP) is essential for viability in most bacteria where it has been studied. However, characterization of the cellular functions and metabolism of c-di-AMP has largely been confined to the class Bacilli, limiting our functional understanding of the molecule among diverse phyla. We identified the cyclase responsible for c-di-AMP synthesis and characterized the molecule's role in survival of darkness in the model photosynthetic cyanobacterium Synechococcus elongatus PCC 7942. In addition to the use of traditional genetic, biochemical, and proteomic approaches, we developed a high-throughput genetic interaction screen (IRB-Seq) to determine pathways where the signaling nucleotide is active. We found that in S. elongatus c-di-AMP is produced by an enzyme of the diadenylate cyclase family, CdaA, which was previously unexplored experimentally. A cdaA-null mutant experiences increased oxidative stress and death during the nighttime portion of day-night cycles, in which potassium transport is implicated. These findings suggest that c-di-AMP is biologically active in cyanobacteria and has non-canonical roles in the phylum including oxidative stress management and day-night survival. The pipeline and analysis tools for IRB-Seq developed for this study constitute a quantitative high-throughput approach for studying genetic interactions.

Published
2018

7. Researchers at Harbin Medical University Release New Data on Myocardial Ischemia (Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion).

Subjects
GUANYLATE cyclase, VASCULAR smooth muscle, MYOCARDIAL ischemia, MEDICAL sciences, HEART diseases
Abstract

Researchers at Harbin Medical University have conducted a study on the effectiveness of Buxu Tongyu (BXTY) Granule, a traditional Chinese medicine, in treating myocardial ischemia. The study found that BXTY alleviates the symptoms of myocardial ischemia by activating the soluble guanylate cyclase (sGC)-3',5'-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. The researchers concluded that BXTY improves the symptoms of acute myocardial ischemia in mice by inducing vasodilation through the activation of the sGC-cGMP-PKG pathway in VSMCs. [Extracted from the article]

Published
2024

8. Studies from Academy of Sciences of the Czech Republic in the Area of Whooping Cough Described (Camp Signaling of bordetella Adenylate Cyclase Toxin Blocks M-csf Triggered Upregulation of Iron Acquisition Receptors On Differentiating...).

Abstract

A report from the Academy of Sciences of the Czech Republic discusses the immune-subversive activities of the pertussis and adenylate cyclase toxins produced by the bacterium Bordetella pertussis, which causes whooping cough. The adenylate cyclase toxin disrupts host defense mechanisms by hijacking cellular signaling pathways and inhibiting the differentiation of inflammatory monocytes into bactericidal macrophages. This toxin also downregulates the expression of receptors involved in iron acquisition, allowing the bacterium to evade host immune responses and proliferate in the airway mucosa. The research suggests a new mechanism by which B. pertussis evades host phagocytes. [Extracted from the article]

Published
2024

9. c‐di‐AMP modulates Listeria monocytogenes central metabolism to regulate growth, antibiotic resistance and osmoregulation

Author

Whiteley, Aaron T, Garelis, Nicholas E, Peterson, Bret N, Choi, Philip H, Tong, Liang, Woodward, Joshua J, and Portnoy, Daniel A

Subjects
Microbiology, Biochemistry and Cell Biology, Biological Sciences, Infectious Diseases, Antimicrobial Resistance, Nutrition, Infection, Acetyl Coenzyme A, Bacterial Proteins, Cell Wall, Dinucleoside Phosphates, Drug Resistance, Microbial, Gene Expression Regulation, Bacterial, Listeria monocytogenes, Osmoregulation, Osmotic Pressure, Phosphorus-Oxygen Lyases, Pyruvate Carboxylase, Second Messenger Systems, Suppression, Genetic, Agricultural and Veterinary Sciences, Medical and Health Sciences, Biological sciences
Abstract

Cyclic diadenosine monophosphate (c-di-AMP) is a conserved nucleotide second messenger critical for bacterial growth and resistance to cell wall-active antibiotics. In Listeria monocytogenes, the sole diadenylate cyclase, DacA, is essential in rich, but not synthetic media and ΔdacA mutants are highly sensitive to the β-lactam antibiotic cefuroxime. In this study, loss of function mutations in the oligopeptide importer (oppABCDF) and glycine betaine importer (gbuABC) allowed ΔdacA mutants to grow in rich medium. Since oligopeptides were sufficient to inhibit growth of the ΔdacA mutant we hypothesized that oligopeptides act as osmolytes, similar to glycine betaine, to disrupt intracellular osmotic pressure. Supplementation with salt stabilized the ΔdacA mutant in rich medium and restored cefuroxime resistance. Additional suppressor mutations in the acetyl-CoA binding site of pyruvate carboxylase (PycA) rescued cefuroxime resistance and resulted in a 100-fold increase in virulence of the ΔdacA mutant. PycA is inhibited by c-di-AMP and these mutations prompted us to examine the role of TCA cycle enzymes. Inactivation of citrate synthase, but not down-stream enzymes suppressed ΔdacA phenotypes. These data suggested that c-di-AMP modulates central metabolism at the pyruvate node to moderate citrate production and indeed, the ΔdacA mutant accumulated six times the concentration of citrate present in wild-type bacteria.

Published
2017

10. Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)

Author

Hallberg, Zachary F, Wang, Xin C, Wright, Todd A, Nan, Beiyan, Ad, Omer, Yeo, Jongchan, and Hammond, Ming C

Subjects
Deltaproteobacteria, Escherichia coli Proteins, Nucleotides, Cyclic, Phosphorus-Oxygen Lyases, Protein Conformation, bacterial signaling, surface sensing, second messengers, cyclic dinucleotides, fluorescent biosensor
Abstract

Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial lifestyle transition from a motile to sessile biofilm-forming state. Since then, the ubiquity of genes encoding GGDEF proteins in bacterial genomes has established the dominance of cdiG signaling in bacteria. However, the observation that proteobacteria encode a large number of GGDEF proteins, nearing 1% of coding sequences in some cases, raises the question of why bacteria need so many GGDEF enzymes. In this study, we reveal that a subfamily of GGDEF enzymes synthesizes the asymmetric signaling molecule cyclic AMP-GMP (cAG or 3', 3'-cGAMP). This discovery is unexpected because GGDEF enzymes function as symmetric homodimers, with each monomer binding to one substrate NTP. Detailed analysis of the enzyme from Geobacter sulfurreducens showed it is a dinucleotide cyclase capable of switching the major cyclic dinucleotide (CDN) produced based on ATP-to-GTP ratios. We then establish through bioinformatics and activity assays that hybrid CDN-producing and promiscuous substrate-binding (Hypr) GGDEF enzymes are found in other deltaproteobacteria. Finally, we validated the predictive power of our analysis by showing that cAG is present in surface-grown Myxococcus xanthus. This study reveals that GGDEF enzymes make alternative cyclic dinucleotides to cdiG and expands the role of this widely distributed enzyme family to include regulation of cAG signaling.

Published
2016

11. A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Author

Skotnicka, Dorota, Smaldone, Gregory T, Petters, Tobias, Trampari, Eleftheria, Liang, Jennifer, Kaever, Volkhard, Malone, Jacob G, Singer, Mitchell, and Søgaard-Andersen, Lotte

Subjects
Genetics, Infectious Diseases, Bacterial Proteins, Cyclic GMP, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Myxococcus xanthus, Phosphorus-Oxygen Lyases, Spores, Bacterial, Starvation, Developmental Biology
Abstract

Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-di-GMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be-at least partially-functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus.

Published
2016

12. Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast

Author

Tang, Man-Cheng, Lin, Hsiao-Ching, Li, Dehai, Zou, Yi, Li, Jian, Xu, Wei, Cacho, Ralph A, Hillenmeyer, Maureen E, Garg, Neil K, and Tang, Yi

Subjects
Biosynthetic Pathways, Cyclization, Diterpenes, Genetic Engineering, Indoles, Molecular Conformation, Phosphorus-Oxygen Lyases, Saccharomyces cerevisiae, Chemical Sciences, General Chemistry
Abstract

The structural diversity and biological activities of fungal indole diterpenes (IDTs) are generated in large part by the IDT cyclases (IDTCs). Identifying different IDTCs from IDT biosynthetic pathways is therefore important toward understanding how these enzymes introduce chemical diversity from a common linear precursor. However, IDTCs involved in the cyclization of the well-known aflavinine subgroup of IDTs have not been discovered. Here, using Saccharomyces cerevisiae as a heterologous host and a phylogenetically guided enzyme mining approach, we combinatorially assembled IDT biosynthetic pathways using IDTCs homologues identified from different fungal hosts. We identified the genetically standalone IDTCs involved in the cyclization of aflavinine and anominine and produced new IDTs not previously isolated. The cyclization mechanisms of the new IDTCs were proposed based on the yeast reconstitution results. Our studies demonstrate heterologous pathway assembly is a useful tool in the reconstitution of unclustered biosynthetic pathways.

Published
2015

13. Local control: a hub-based model for the c-di-GMP network.

Author

Vasenina A, Fu Y, O'Toole GA, and Mucha PJ

Subjects
Protein Interaction Maps, Gene Expression Regulation, Bacterial, Phosphorus-Oxygen Lyases, Escherichia coli Proteins, Cyclic GMP analogs & derivatives, Cyclic GMP metabolism, Biofilms growth & development, Pseudomonas fluorescens genetics, Pseudomonas fluorescens metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism
Abstract

The genome of Pseudomonas fluorescens encodes >50 proteins predicted to play a role in bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP)-mediated biofilm formation. We built a network representation of protein-protein interactions and extracted key information via multidimensional scaling (i.e., principal component analysis) of node centrality measures, which measure features of proteins in a network. Proteins of different domain types (diguanylate cyclase, dual domain, phosphodiesterase, PilZ) exhibit unique network behavior and can be accurately classified by their network centrality values (i.e., roles in the network). The predictive power of protein-protein interactions in biofilm formation indicates the possibility of localized pools of c-di-GMP. A regression model showed a statistically significant impact of protein-protein interactions on the extent of biofilm formation in various environments. These results highlight the importance of a localized c-di-GMP signaling, extend our understanding of signaling by this second messenger beyond the current "Bow-tie Model," support a newly proposed "Hub Model," and suggest future avenues of investigation., Competing Interests: The authors declare no conflict of interest.

Published
2024
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14. Mitochondrial transcription factor A (TFAM) has 5'-deoxyribose phosphate lyase activity in vitro.

Author

Zhao W, Hussen AS, Freudenthal BD, Suo Z, and Zhao L

Subjects
Humans, DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism, Lysine, DNA Repair, DNA Polymerase gamma metabolism, DNA, Mitochondrial metabolism, DNA-Binding Proteins metabolism, Transcription Factors, Mitochondrial Proteins metabolism, Lyases metabolism, DNA Polymerase beta metabolism, Phosphorus-Oxygen Lyases
Abstract

Mitochondrial DNA (mtDNA) plays a key role in mitochondrial and cellular functions. mtDNA is maintained by active DNA turnover and base excision repair (BER). In BER, one of the toxic repair intermediates is 5'-deoxyribose phosphate (5'dRp). Human mitochondrial DNA polymerase γ has weak dRp lyase activities, and another known dRp lyase in the nucleus, human DNA polymerase β, can also localize to mitochondria in certain cell and tissue types. Nonetheless, whether additional proteins have the ability to remove 5'dRp in mitochondria remains unknown. Our prior work on the AP lyase activity of mitochondrial transcription factor A (TFAM) has prompted us to examine its ability to remove 5'dRp residues in vitro. TFAM is the primary DNA-packaging factor in human mitochondria and interacts with mitochondrial DNA extensively. Our data demonstrate that TFAM has the dRp lyase activity with different DNA substrates. Under single-turnover conditions, TFAM removes 5'dRp residues at a rate comparable to that of DNA polymerase (pol) β, albeit slower than that of pol λ. Among the three proteins examined, pol λ shows the highest single-turnover rates in dRp lyase reactions. The catalytic effect of TFAM is facilitated by lysine residues of TFAM via Schiff base chemistry, as evidenced by the observation of dRp-lysine adducts in mass spectrometry experiments. The catalytic effect of TFAM observed here is analogous to the AP lyase activity of TFAM reported previously. Together, these results suggest a potential role of TFAM in preventing the accumulation of toxic DNA repair intermediates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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15. RNA-Based Fluorescent Biosensors for Live Cell Imaging of Second Messenger Cyclic di-AMP

Author

Kellenberger, Colleen A, Chen, Chen, Whiteley, Aaron T, Portnoy, Daniel A, and Hammond, Ming C

Subjects
Engineering, Chemical Sciences, Infectious Diseases, Digestive Diseases, Prevention, Emerging Infectious Diseases, Vaccine Related, Biotechnology, Infection, Biosensing Techniques, Cell Survival, Clostridioides difficile, Dinucleoside Phosphates, Enzyme Activation, Fluorescence, Listeria monocytogenes, Methanocaldococcus, Phosphoric Diester Hydrolases, Phosphorus-Oxygen Lyases, RNA, Riboswitch, Second Messenger Systems, Clostridium difficile, General Chemistry, Chemical sciences
Abstract

Cyclic di-AMP (cdiA) is a second messenger predicted to be widespread in Gram-positive bacteria, some Gram-negative bacteria, and Archaea. In the human pathogen Listeria monocytogenes, cdiA is an essential molecule that regulates metabolic function and cell wall homeostasis, and decreased levels of cdiA result in increased antibiotic susceptibility. We have generated fluorescent biosensors for cdiA through fusion of the Spinach2 aptamer to ligand-binding domains of cdiA riboswitches. The biosensor was used to visualize intracellular cdiA levels in live L. monocytogenes strains and to determine the catalytic domain of the phosphodiesterase PdeA. Furthermore, a flow cytometry assay based on this biosensor was used to screen for diadenylate cyclase activity and confirmed the enzymatic activity of DisA-like proteins from Clostridium difficile and Methanocaldococcus jannaschii. Thus, we have expanded the development of RNA-based biosensors for in vivo metabolite imaging in Gram-positive bacteria and have validated the first dinucleotide cyclase from Archaea.

Published
2015

16. "Pertussis Vaccine" in Patent Application Approval Process (USPTO 20240181030).

Abstract

ModernaTX Inc. has filed a patent application for a ribonucleic acid (RNA) vaccine that targets whooping cough, diphtheria, and tetanus. The vaccine uses messenger RNA (mRNA) to instruct the body to produce specific proteins that can fight these diseases. The vaccine contains multiple mRNA polynucleotides that encode various antigenic polypeptides for Bordetella pertussis. It has the potential to treat and prevent infections caused by different strains and genotypes of these diseases. The patent application includes claims for different compositions of the vaccine, as well as specific amino acid and nucleotide sequences for the antigenic polypeptides. [Extracted from the article]

Published
2024

17. Patent Issued for Fused pyrazine derivatives as A2A / A2B inhibitors (USPTO 11999740).

Abstract

A patent has been issued for fused pyrazine derivatives as A2A/A2B inhibitors. Adenosine is a signaling molecule that can modulate immune responses, and it plays a vital role in various physiological functions. Adenosine receptors, specifically A2A and A2B, have different effects on immune and inflammatory cells. The invention aims to develop new adenosine receptor selective ligands for the treatment of diseases such as cancer, inflammatory diseases, cardiovascular diseases, and neurodegenerative diseases. The patent provides compounds of Formula (I) as potential inhibitors. [Extracted from the article]

Published
2024

18. Researchers at Fudan University Have Published New Study Findings on Guanylate Cyclase (Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized,...).

Subjects
GUANYLATE cyclase, PHARMACOKINETICS, RESEARCH personnel, PHARMACODYNAMICS, VOLUNTEERS, HEART failure
Abstract

A new report discusses research findings on guanylate cyclase, a potential treatment for heart failure. The study evaluated the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase stimulator, in healthy volunteers. The results showed that HEC95468 was safe and tolerable, with participants experiencing mild side effects such as headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal issues. The study concluded that these findings support further clinical trials of HEC95468 for the treatment of heart failure and pulmonary arterial hypertension. [Extracted from the article]

Published
2024

19. Cedars Sinai Medical Center Researcher Releases New Data on Cystic Fibrosis (Adenylate cyclase 6 targets in Mucociliary Clearance).

Subjects
ADENYLATE cyclase, CYSTIC fibrosis, MUCOCILIARY system, MEDICAL research personnel, MEDICAL centers
Abstract

A recent report from Cedars Sinai Medical Center discusses the impairment of mucociliary clearance (MCC) in cystic fibrosis (CF) and its impact on lung function. The researchers identified a key role for the enzyme Adenylate cyclase 6 (AC6) in MCC, specifically in regulating CFTR chloride channels and ciliary beat frequency. They developed specific activators of AC6 that improved MCC in CF explant tissues and cells. These findings have the potential to improve our understanding of epithelial biology and develop therapeutic agents for mucus clearance defects in CF and other respiratory diseases. [Extracted from the article]

Published
2024

20. Investigators at Chongqing Medical University Detail Findings in Adenylate Cyclase (Regulation of Cardiac Fibrosis In Mice With Tac/doca-induced Hfpef By resistin-like Molecule Gamma and adenylate Cyclase 1).

Subjects
ADENYLATE cyclase, HEART fibrosis, HEART failure, MOLECULES, SIGNAL peptides
Abstract

A research report from Chongqing Medical University in China discusses the findings on the regulation of cardiac fibrosis in mice with heart failure with preserved ejection fraction (HFpEF). The study explores fibrosis-related genes and pathways in the pathophysiological process of HFpEF and identifies resistin-like molecule gamma (Relmg) and adenylate cyclase 1 (Adcy1) as potential targets for HFpEF treatment. The research suggests that myocardial fibrosis is significantly upregulated in HFpEF mice compared to healthy controls, and the expression levels of Relmg and Adcy1 are significantly higher and lower, respectively, in the heart tissues of HFpEF mice. [Extracted from the article]

Published
2024

21. Reports Outline Heart Failure Research from Dokuz Eylul University (The efficacy and safety of soluble guanylate cyclase modulation in patients with heart failure: a comprehensive meta-analysis of randomized controlled trials).

Subjects
GUANYLATE cyclase, RANDOMIZED controlled trials, HEART failure, CARDIAC research, HEART failure patients
Abstract

A meta-analysis of randomized controlled trials conducted by researchers at Dokuz Eylul University examined the efficacy and safety of soluble guanylate cyclase (sGC) modulation in patients with heart failure. The analysis included 10 trials with a total of 7,526 heart failure patients. The results showed that the use of sGC modulators did not significantly affect the risk of all-cause mortality compared to placebo. However, there was a trend towards an increase in serious adverse events, hypotension, and anemia with sGC modulation. The study also found that sGC modulation had a neutral effect on NT-proBNP levels, 6MWD, and mortality, but it did improve quality of life in certain domains. [Extracted from the article]

Published
2024

22. A Structural Basis for the Regulation of an H‑NOX-Associated Cyclic-di-GMP Synthase/Phosphodiesterase Enzyme by Nitric Oxide-Bound H‑NOX

Author

Lahiri, Tanaya, Luan, Bowu, Raleigh, Daniel P, and Boon, Elizabeth M

Subjects
Biotechnology, Infectious Diseases, Emerging Infectious Diseases, Infection, Bacterial Proteins, Biofilms, Cyclic GMP, Escherichia coli Proteins, Heme, Models, Molecular, Molecular Structure, Mutagenesis, Site-Directed, Mutant Proteins, Nitric Oxide, Oxygen, Phosphoric Diester Hydrolases, Phosphorus-Oxygen Lyases, Shewanella, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology
Abstract

Biofilms are surface-attached communities of bacteria enclosed in a polysaccharide matrix. Bacteria in a biofilm are extremely resistant to antibiotics. Several recent reports have linked the signaling molecule nitric oxide (NO) with biofilm dispersal. We have previously reported that an H-NOX (heme-nitric oxide/oxygen binding) protein in the biofilm-dwelling bacterium Shewanella woodyi mediates NO-induced biofilm dispersal. In S. woodyi, H-NOX (SwH-NOX) is cocistronic with a gene encoding a dual-functioning diguanylate cyclase/phosphodiesterase enzyme, designated here as HaCE (H-NOX-associated cyclic-di-GMP processing enzyme). Enzymes such as these are responsible for regulating the intracellular concentrations of cyclic-di-GMP, a secondary signaling molecule essential to biofilm formation in bacteria. We have demonstrated that NO-bound SwH-NOX regulates both enzymatic activities of SwHaCE, resulting in decreased cellular cyclic-di-GMP levels and disruption of biofilm formation. Thus, H-NOX/HaCE represents a potential drug target for regulating biofilm formation. In this work, the SwH-NOX surface residues critical for the formation of a protein complex with SwHaCE are identified using nuclear magnetic resonance, fluorescence quenching, and cosedimentation. Enzyme assays confirm this protein-protein interface and its importance for H-NOX/HaCE function.

Published
2014

23. New Nerve Growth Factors Study Results from Boston University Described [Pituitary Adenylate Cyclase-activating Polypeptide (Pacap) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking In Mice].

Abstract

A recent study conducted by researchers at Boston University explores the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in heavy alcohol drinking in mice. The study found that chronic exposure to ethanol leads to increased levels of PACAP in the bed nucleus of the stria terminalis (BNST), a brain region associated with excessive drinking and anxiety-like behavior. Additionally, the inhibition of PACAP neuronal afferents to the BNST was found to reduce heavy ethanol drinking. These findings suggest that the PACAP system in the BNST may be a potential target for novel therapies for alcohol use disorder. [Extracted from the article]

Published
2024

24. Researcher at University of Florence Discusses Research in Guanylate Cyclase (Pharmacological Stimulation of Soluble Guanylate Cyclase Counteracts the Profibrotic Activation of Human Conjunctival Fibroblasts).

Abstract

A study conducted at the University of Florence in Italy explores the potential use of soluble guanylate cyclase (sGC) stimulation as a treatment for conjunctival fibrosis, a condition associated with various eye diseases. The researchers found that sGC stimulation suppressed the differentiation of conjunctival fibroblasts into myofibroblasts, which is a key factor in abnormal wound healing and scar formation. The study suggests that pharmacological sGC stimulation could be a promising approach to treating conjunctival fibrotic conditions. Further research is needed to explore the feasibility of sGC stimulators as therapeutic compounds. [Extracted from the article]

Published
2024

25. Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis in Drosophila.

Abstract

A recent preprint abstract discusses the characterization of the ion transport peptide (ITP) signaling system in Drosophila. The study reveals the expression of three different ITP isoforms in the nervous system and peripheral tissues. It also identifies Gyc76C, a membrane guanylate cyclase, as the receptor for ITPa, an anti-diuretic hormone. Knockdown of Gyc76C affects osmoregulation and metabolic homeostasis in Drosophila. The study provides insights into how a small set of neurons integrates diverse inputs to maintain systemic homeostasis in Drosophila. [Extracted from the article]

Published
2024

26. Patent Issued for Polynucleotides encoding monoclonal antibodies binding to human pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) and methods of making thereof (USPTO 11891435).

Subjects
PITUITARY adenylate cyclase activating polypeptide, INVENTORS, NUCLEIC acids, MONOCLONAL antibodies, DIAMINO amino acids, BLOOD proteins
Abstract

Amgen Inc. has been issued a patent for polynucleotides that encode monoclonal antibodies targeting the human pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1). These antibodies have been found to have enhanced inhibitory potency against human PAC1 and can be used to inhibit PACAP-induced activation of PAC1, reduce vasodilation, and treat symptoms of migraine and other vascular headaches. The patent provides detailed information on the specific sequences of the antibodies and antigen-binding fragments, as well as methods for producing them. This research has potential implications for the development of therapies for pain and migraine. [Extracted from the article]

Published
2024

27. Patent Issued for Pyrazolopyridines and triazolopyridines as A2A / A2B inhibitors (USPTO 11884665).

Abstract

Incyte Corporation has been issued a patent for pyrazolopyridines and triazolopyridines as A2A/A2B inhibitors. Adenosine is an extracellular signaling molecule that plays a role in immune responses and various physiological functions. The patent aims to develop adenosine receptor selective ligands for the treatment of diseases such as cancer, inflammatory diseases, cardiovascular diseases, and neurodegenerative diseases. The patent includes methods of inhibiting adenosine receptors and treating diseases associated with abnormal expression of these receptors, such as bladder cancer, lung cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, and head and neck cancer. [Extracted from the article]

Published
2024

28. Researchers from Sao Francisco University Medical School Publish Findings in Sickle Cell Anemia (Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease).

Subjects
GUANYLATE cyclase, SICKLE cell anemia, PRIAPISM, MEDICAL schools, RESEARCH personnel
Abstract

Researchers from Sao Francisco University Medical School in Brazil have published findings on the treatment of priapism associated with sickle cell disease (SCD). Priapism is a common complication in SCD, affecting up to 48% of male patients. The researchers highlight the need for preventative rather than reactive treatments for SCD-related priapism and suggest that compounds that stimulate and activate soluble guanylate cyclase (sGC) may be potential therapeutic candidates. They also discuss the impact of intravascular hemolysis and oxidative stress on priapism pathophysiology in SCD. This research provides new insights into the treatment of priapism in SCD and may have beneficial therapeutic effects. [Extracted from the article]

Published
2024

30. Researchers Submit Patent Application, "Agonists Of Guanylate Cyclase Useful For The Treatment Of Gastrointestinal Disorders, Inflammation, Cancer And Other Disorders", for Approval (USPTO 20240002440).

Abstract

A patent application has been submitted for the approval of "Agonists Of Guanylate Cyclase Useful For The Treatment Of Gastrointestinal Disorders, Inflammation, Cancer And Other Disorders." The application discusses the role of uroguanylin and guanylin peptides in regulating fluid and electrolyte transport in the gastrointestinal (GI) tract. It also highlights the importance of the balance between cell proliferation and apoptosis in maintaining the homeostasis of the GI mucosa. The application suggests that disruptions in this renewal process may lead to GI inflammation and cancer. Additionally, it mentions the differences between inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, and irritable bowel syndrome (IBS). The patent application discusses the development of agonists of guanylate cyclase receptor for the treatment of various conditions. The peptides described in the application can be used to increase intracellular levels of cGMP, which has therapeutic effects on gastrointestinal disorders, inflammatory disorders, lung disorders, cancer, cardiac disorders, eye disorders, oral disorders, blood disorders, liver disorders, skin disorders, prostate disorders, endocrine disorders, and obesity. The peptides may be administered in pharmaceutical compositions and can be used in combination with inhibitors of cGMP-specific phosphodiesterase. The application also mentions the use of anti-inflammatory agents in conjunction with the peptides. [Extracted from the article]

Published
2024

31. Researchers at University of Electronic Science and Technology of China Have Published New Study Findings on Guanylate Cyclase (Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive...).

Subjects
GUANYLATE cyclase, RESEARCH personnel, CARDIAC research, LYASES, SIGNAL peptides
Abstract

A new study conducted by researchers at the University of Electronic Science and Technology of China explores the targets of guanylate cyclase agonists in cardiovascular and digestive diseases. The study highlights the potential therapeutic benefits of these drugs and discusses recent research progress in this area. The researchers provide an overview of representative drugs and current findings, shedding light on the underlying signaling mechanisms. This information is valuable for individuals interested in cardiology and cardiovascular research. [Extracted from the article]

Published
2024

32. Characterisation of sequence–structure–function space in sensor–effector integrators of phytochrome-regulated diguanylate cyclases

Author

Cornelia Böhm, Geoffrey Gourinchas, Sophie Zweytick, Elvira Hujdur, Martina Reiter, Sara Trstenjak, Christoph Wilhelm Sensen, and Andreas Winkler

Subjects
Bacterial Proteins, Phytochrome, Phosphorus-Oxygen Lyases, Physical and Theoretical Chemistry, Phylogeny
Abstract

Understanding the relationship between protein sequence, structure and function is one of the fundamental challenges in biochemistry. A direct correlation, however, is often not trivial since protein dynamics also play an important functional role—especially in signal transduction processes. In a subfamily of bacterial light sensors, phytochrome-activated diguanylate cyclases (PadCs), a characteristic coiled-coil linker element connects photoreceptor and output module, playing an essential role in signal integration. Combining phylogenetic analyses with biochemical characterisations, we were able to show that length and composition of this linker determine sensor–effector function and as such are under considerable evolutionary pressure. The linker length, together with the upstream PHY-specific domain, influences the dynamic range of effector activation and can even cause light-induced enzyme inhibition. We demonstrate phylogenetic clustering according to linker length, and the development of new linker lengths as well as new protein function within linker families. The biochemical characterisation of PadC homologs revealed that the functional coupling of PHY dimer interface and linker element defines signal integration and regulation of output functionality. A small subfamily of PadCs, characterised by a linker length breaking the coiled-coil pattern, shows a markedly different behaviour from other homologs. The effect of the central helical spine on PadC function highlights its essential role in signal integration as well as direct regulation of diguanylate cyclase activity. Appreciation of sensor–effector linkers as integrator elements and their coevolution with sensory modules is a further step towards the use of functionally diverse homologs as building blocks for rationally designed optogenetic tools. Graphical abstract

Published
2022

33. Studies from University of Debrecen Provide New Data on Nerve Growth Factors [Impact Assessment of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Hemostatic Sponge on Vascular Anastomosis Regeneration in Rats].

Abstract

A study conducted by researchers at the University of Debrecen in Hungary has examined the impact of pituitary adenylate cyclase-activating polypeptide (PACAP) and a hemostatic sponge on the regeneration of vascular anastomosis in rats. The researchers found that PACAP can aid in healing by reducing inflammation, apoptosis, and oxidative stress. The study also found that the combined use of PACAP and the hemostatic sponge was beneficial for vascular regeneration, increasing elasticity and tensile strength. This research provides new data on nerve growth factors and their potential applications in microvascular surgery. [Extracted from the article]

Published
2023

34. Patent Issued for Ultra-pure agonists of guanylate cyclase C, method of making and using same (USPTO 11834521).

Abstract

A patent has been issued for ultra-pure agonists of guanylate cyclase C, which are peptides that have potential applications in the treatment of gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome. The patent describes the role of guanylate cyclase C in regulating fluid and electrolyte balance in the intestines and the potential therapeutic benefits of targeting this pathway. The inventors have developed methods for purifying these peptides, which can improve their effectiveness and reduce impurities. This patent provides valuable insights for researchers and pharmaceutical companies interested in developing new treatments for gastrointestinal conditions. [Extracted from the article]

Published
2023

35. "Imidazopyrimidines And Triazolopyrimidines As A2a / A2b Inhibitors" in Patent Application Approval Process (USPTO 20230357255).

Abstract

A patent application has been filed for the development of compounds that inhibit adenosine receptors A2A and A2B. Adenosine is a signaling molecule that plays a role in various physiological functions and can modulate immune responses. The A2A receptor has anti-inflammatory effects, while the A2B receptor is mainly expressed in the gastrointestinal tract, bladder, lung, and mast cells. Inhibiting these receptors has shown potential in suppressing tumor growth and increasing the presentation of tumor antigens. The safety profile of blocking these receptors has been studied in knockout mice, with A2A knockout mice showing no inflammation at baseline and A2B knockout mice exhibiting increased inflammation. The compounds developed in this patent application could be used for the treatment of diseases such as cancer, inflammatory diseases, cardiovascular diseases, and neurodegenerative diseases. [Extracted from the article]

Published
2023

36. Research on Sudden Infant Death Syndrome Reported by Researchers at University of Pecs School of Medicine [Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation].

Abstract

Researchers at the University of Pecs School of Medicine in Hungary have conducted a study on sudden infant death syndrome (SIDS). SIDS is a significant cause of post-neonatal mortality, but its underlying mechanisms are still unclear. The researchers propose that pituitary adenylate cyclase-activating polypeptide (PACAP) deficiency may be a promising avenue for studying SIDS. PACAP is a neuropeptide that plays a role in various physiological functions, and its absence has been linked to increased neonatal mortality. This mini-review provides a comprehensive synthesis of PACAP-related research in relation to SIDS. [Extracted from the article]

Published
2023

37. Patent Application Titled "Ultra-Pure Agonists Of Guanylate Cyclase C, Method Of Making And Using Same" Published Online (USPTO 20230340023).

Abstract

The patent application titled "Ultra-Pure Agonists Of Guanylate Cyclase C, Method Of Making And Using Same" discusses the purification process of a peptide called plecanatide, which is used to treat inflammatory conditions, particularly those affecting the gastrointestinal tract. The process involves adsorbing the peptide onto a polymeric adsorbent column and eluting it with an alcohol aqueous solution, resulting in a purified peptide that is free of contaminants and has specific characteristics such as low bulk density and low levels of impurities. The application also mentions the potential use of an oral formulation of the purified peptide in treating conditions like colon cancer, Crohn's disease, and ulcerative colitis. [Extracted from the article]

Published
2023

38. Findings from Nanjing Normal University Reveals New Findings on Fatty Liver Disease (Gamma-glutamylcysteine Alleviates Insulin Resistance and Hepatic Steatosis By Regulating Adenylate Cyclase and Igf-1r/irs1/pi3k/akt Signaling Pathways).

Abstract

Keywords: Jiangsu; People's Republic of China; Asia; Adenylate Cyclase; Diseases and Conditions; Endocrine System Diseases and Conditions; Enzymes and Coenzymes; Fatty Liver Disease; Glucose Metabolism Disorders; Health and Medicine; Hyperinsulinism; Insulin Resistance; Intracellular Signaling Peptides and Proteins; Liver Diseases and Conditions; Nutritional and Metabolic Diseases and Conditions; Peptide Hormones; Peptide Proteins; Phosphorus-Oxygen Lyases; Proinsulin; Steatosis EN Jiangsu People's Republic of China Asia Adenylate Cyclase Diseases and Conditions Endocrine System Diseases and Conditions Enzymes and Coenzymes Fatty Liver Disease Glucose Metabolism Disorders Health and Medicine Hyperinsulinism Insulin Resistance Intracellular Signaling Peptides and Proteins Liver Diseases and Conditions Nutritional and Metabolic Diseases and Conditions Peptide Hormones Peptide Proteins Phosphorus-Oxygen Lyases Proinsulin Steatosis 94 94 1 10/09/23 20231009 NES 231009 2023 OCT 9 (NewsRx) -- By a News Reporter-Staff News Editor at Diabetes Week -- Investigators publish new report on Liver Diseases and Conditions - Fatty Liver Disease. Keywords for this news article include: Jiangsu, People's Republic of China, Asia, Adenylate Cyclase, Diseases and Conditions, Endocrine System Diseases and Conditions, Enzymes and Coenzymes, Fatty Liver Disease, Glucose Metabolism Disorders, Health and Medicine, Hyperinsulinism, Insulin Resistance, Intracellular Signaling Peptides and Proteins, Liver Diseases and Conditions, Nutritional and Metabolic Diseases and Conditions, Peptide Hormones, Peptide Proteins, Phosphorus-Oxygen Lyases, Proinsulin, Steatosis, Nanjing Normal University. [Extracted from the article]

Published
2023

39. Genome-wide mapping of Vibrio cholerae VpsT binding identifies a mechanism for c-di-GMP homeostasis

Author

Thomas Guest, David C. Grainger, James R. J. Haycocks, and Gemma Z. L. Warren

Subjects
Operon, Diguanylate cyclase activity, AcademicSubjects/SCI00010, Regulatory Sequences, Nucleic Acid, medicine.disease_cause, chemistry.chemical_compound, Bacterial Proteins, Guanosine monophosphate, medicine, Genetics, Homeostasis, Binding site, Transcription factor, Cyclic GMP, Vibrio cholerae, Mutation, biology, Chemistry, Escherichia coli Proteins, Gene regulation, Chromatin and Epigenetics, Cell biology, biology.protein, Diguanylate cyclase, Phosphorus-Oxygen Lyases, Protein Binding, Transcription Factors
Abstract

Many bacteria use cyclic dimeric guanosine monophosphate (c-di-GMP) to control changes in lifestyle. The molecule, synthesised by proteins having diguanylate cyclase activity, is often a signal to transition from motile to sedentary behaviour. In Vibrio cholerae, c-di-GMP can exert its effects via the transcription factors VpsT and VpsR. Together, these proteins activate genes needed for V. cholerae to form biofilms. In this work, we have mapped the genome-wide distribution of VpsT in a search for further regulatory roles. We show that VpsT binds 23 loci and recognises a degenerate DNA palindrome having the consensus 5’-W-5R-4[CG]-3Y-2W-1W+1R+2[GC]+3Y+4W+5-3’. Most genes targeted by VpsT encode functions related to motility, biofilm formation, or c-di-GMP metabolism. Most notably, VpsT activates expression of the vpvABC operon that encodes a diguanylate cyclase. This creates a positive feedback loop needed to maintain intracellular levels of c-di-GMP. Mutation of the key VpsT binding site, upstream of vpvABC, severs the loop and c-di-GMP levels fall accordingly. Hence, as well as relaying the c-di-GMP signal, VpsT impacts c-di-GMP homeostasis.

Published
2021

40. Heme-Edge Residues Modulate Signal Transduction within a Bifunctional Homo-Dimeric Sensor Protein

Author

Dayna C Patterson, Emily E. Weinert, Yilin Liu, Neela H. Yennawar, James R. Kincaid, Sayan Das, and Jean Paul Armache

Subjects
Hemeproteins, Models, Molecular, Protein Conformation, alpha-Helical, Static Electricity, Population, Gene Expression, Heme, 010402 general chemistry, 01 natural sciences, Biochemistry, Substrate Specificity, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, Bacterial Proteins, Guanosine monophosphate, Escherichia coli, Protein Interaction Domains and Motifs, Phosphofructokinase 2, Amino Acid Sequence, DCPG, Enzyme kinetics, education, Cyclic GMP, 030304 developmental biology, 0303 health sciences, education.field_of_study, Binding Sites, Sequence Homology, Amino Acid, Phosphoric Diester Hydrolases, Escherichia coli Proteins, Recombinant Proteins, 0104 chemical sciences, Oxygen, Kinetics, Amino Acid Substitution, chemistry, Biophysics, Protein Conformation, beta-Strand, Phosphorus-Oxygen Lyases, Protein Multimerization, Signal transduction, Paenibacillus, Sequence Alignment, Protein Binding, Signal Transduction
Abstract

Bifunctional enzymes, which contain two domains with opposing enzymatic activities, are widely distributed in bacteria, but the regulatory mechanism(s) that prevent futile cycling are still poorly understood. The recently described bifunctional enzyme, DcpG, exhibits unusual heme properties and is surprisingly able to differentially regulate its two cyclic dimeric guanosine monophosphate (c-di-GMP) metabolic domains in response to heme gaseous ligands. Mutagenesis of heme-edge residues was used to probe the heme pocket and resulted in decreased O2 dissociation kinetics, identifying roles for these residues in modulating DcpG gas sensing. In addition, the resonance Raman spectra of the DcpG wild type and heme-edge mutants revealed that the mutations alter the heme electrostatic environment, vinyl group conformations, and spin state population. Using small-angle X-ray scattering and negative stain electron microscopy, the heme-edge mutations were demonstrated to cause changes to the protein conformation, which resulted in altered signaling transduction and enzyme kinetics. These findings provide insights into molecular interactions that regulate DcpG gas sensing as well as mechanisms that have evolved to control multidomain bacterial signaling proteins.

Published
2021

41. High-specificity local and global c-di-GMP signaling

Author

Regine Hengge

Subjects
Microbiology (medical), Flexibility (engineering), 0303 health sciences, 030306 microbiology, Effector, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Computational biology, Biology, GGDEF domain, Microbiology, Phenotype, 03 medical and health sciences, Signaling network, Infectious Diseases, Bacterial Proteins, Biofilms, Virology, Second messenger system, biology.protein, Diguanylate cyclase, Phosphorus-Oxygen Lyases, Signal transduction, Cyclic GMP, 030304 developmental biology
Abstract

The striking multiplicity, signal input diversity, and output specificity of c-di-GMP signaling proteins in many bacteria has brought second messenger signaling back onto the agenda of contemporary microbiology. How can several signaling pathways act in parallel in a specific manner if all of them use the same diffusible second messenger present at a certain global cellular concentration? Recent research has now shown that bacteria achieve this by flexibly combining modes of local and global c-di-GMP signaling in complex signaling networks. Three criteria have to be met to define local c-di-GMP signaling: specific knockout phenotypes, direct interactions between proteins involved, and actual cellular c-di-GMP levels remaining below the Kd of effectors. Adaptive changes in signaling network architecture can further enhance signaling flexibility.

Published
2021

42. Elongation factor P modulates

Author

Quan, Guo, Binbin, Cui, Mingfang, Wang, Xia, Li, Huihui, Tan, Shihao, Song, Jianuan, Zhou, Lian-Hui, Zhang, and Yinyue, Deng

Subjects
Acinetobacter baumannii, Bacterial Proteins, Virulence, Phosphoric Diester Hydrolases, Biofilms, Escherichia coli Proteins, Guanosine Monophosphate, Gene Expression Regulation, Bacterial, Phosphorus-Oxygen Lyases, Peptide Elongation Factors, Cyclic GMP
Abstract

Cyclic diguanosine monophosphate (c-di-GMP) is widely used by bacteria to control biological functions in response to diverse signals or cues. A previous study showed that potential c-di-GMP metabolic enzymes play a role in the regulation of biofilm formation and motility in

Published
2022

43. A psychometric evaluation of the National Stressful Events Survey for PTSD-Short Scale (NSESSS-PTSD) among Korean psychiatric outpatients

Author

Ilbin Kim, Daeho Kim, Nam Hee Kim, and Joo Eon Park

Subjects
Adult, Stress Disorders, Post-Traumatic, Psychometrics, Phenylketonurias, Outpatients, Republic of Korea, Humans, Reproducibility of Results, Phosphorus-Oxygen Lyases
Abstract

The National Stressful Events Survey for PTSD-Short Scale (NSESSS-PTSD) is a brief screening measure for DSM-5 PTSD that has not been evaluated for its psychometric properties in clinical population. We developed a Korean version of the original English scale through translation-back translation process and examined its reliability and validity among treatment-seeking adults at a psychiatric outpatient unit of a university-affiliated hospital in South Korea. The sample comprised adults diagnosed with PTSD (in/i = 100) and other psychiatric disorders (in/i = 134). The NSESSS-PTSD, the PTSD Checklist for DSM-5 (PCL-5), the Beck Depression Inventory-II (BDI-II), and the Beck Anxiety Inventory (BAI) were used to determine validity and reliability. The findings show modest test-retest reliability (ir/i = .43), good internal consistency (Cronbach'siα/i = .81), high convergent validity (ir/i = .78) with PCL-5 and good concurrent validity with the BDI (ir/i = .55) and BAI (ir/i = .50), respectively. A cut-off score of 16 best predicted PTSD from other psychiatric disorders with specificity of .90 and sensitivity of .87. This study reveals sound psychometric properties of the Korean version of the NSESSS-PTSD and supports its use in the clinical population.La Encuesta Nacional de Eventos Estresantes para PTSD- Escala Corta (NSESSS-PTSD por sus siglas en inglés) es una medida de tamizaje breve para el TEPT del DSM-5 cuyas propiedades psicométricas no se han evaluado en la población clínica. Desarrollamos una versión coreana de la escala original en inglés a través de un proceso de traducción-retrotraducción y examinamos su confiabilidad y validez entre adultos que buscaban tratamiento en una unidad de consulta ambulatoria psiquiátrica de un hospital afiliado a la universidad en Corea del Sur. La muestra incluía adultos diagnosticados con TEPT (in/i = 100) y otros trastornos psiquiátricos (in/i = 134). Se utilizaron la NSESSS-PTSD, la lista de Chequeo del TEPT según el DSM-5 (PCL-5), el Inventario de Depresión de Beck-II (BDI-II) y el Inventario de Ansiedad de Beck (BAI) para determinar su validez y confiabilidad. Los resultados muestran una modesta confiabilidad test-retest (r = .43), una buena consistencia interna (iα/ide Cronbach = .81), una alta validez convergente (ir/i = 78) con el PCL-5 y una buena validez concurrente con el BDI (ir/i = .55) y el BAI (ir/i = .50), respectivamente. Una puntuación de corte de 16 predijo mejor el TEPT de otros trastornos psiquiátricos con una especificidad de .90 y una sensibilidad de .87. Este estudio revela sólidas propiedades psicométricas de la versión coreana de la NSESSS-PTSD y apoya su uso en la población clínica.国家应激事件调查PTSD简短量表 (NSESSS-PTSD) 是一项针对 DSM-5 PTSD 的简短筛查测量，尚未对其在临床人群中的心理测量特性进行评估。我们通过翻译回译过程开发了原始英语量表的韩语版，并在韩国一家大学附属医院的精神病门诊部考查了它在寻求治疗的成年人中的信效度。样本包括被诊断患有 PTSD (in/i = 100) 和其他精神疾病 (in/i = 134) 的成年人。 使用NSESSS-PTSD、DSM-5 PTSD 检查表(PCL-5) 、贝克抑郁量表-II (BDI-II) 和贝克焦虑量表 (BAI) 确定有效性和可靠性。研究结果显示出中等的重测信度 (ir/i = .43)、良好的内部一致性 (Cronbach'siα/i = .81)、与PCL-5 的高收敛效度 (ir/i = .78) 和与BDI (ir/i = . 55) 以及和 BAI (ir/i = .50)的良好同时效度。从其他精神疾病最佳预测 PTSD 的临界分为 16，特异性为 0.90，敏感性为 0.87。本研究揭示了韩语版 NSESSS-PTSD 的良好心理测量特性，并支持其在临床人群中的应用.

Published
2022

44. Childhood trauma, attachment orientation and Complex PTSD (CPTSD) symptoms in a clinical sample: Implications for treatment

Author

Thanos Karatzias, Philip Hyland, Julian D. Ford, Marylene Cloitre, Claire Fyvie, Graeme Grandison, and Mark Shevlin

Subjects
Adult, 050103 clinical psychology, 05 social sciences, Life events, Complex ptsd, 030227 psychiatry, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Psychiatry and Mental health, Posttraumatic stress, 0302 clinical medicine, Adverse Childhood Experiences, Orientation (mental), Phenylketonurias, Developmental and Educational Psychology, Attachment theory, Humans, 0501 psychology and cognitive sciences, Self Report, Phosphorus-Oxygen Lyases, Psychology, Personality, Clinical psychology
Abstract

Although there has been significant work on the association between posttraumatic stress disorder (PTSD) and attachment orientation, this is less the case for complex PTSD (CPTSD). The primary aim of this paper was to assess the strength of the association between the four adult attachment styles (i.e., secure, dismissing, preoccupied, and fearful) and severity of CPTSD symptoms (i.e., symptoms of PTSD and disturbances in self-organization [DSO]). We hypothesized that attachment orientation would be more strongly associated with DSO symptoms compared to PTSD symptoms. A trauma exposed clinical sample (N = 331) completed self-report measures of traumatic life events, CPTSD symptoms, and attachment orientation. It was found that secure attachment and fearful attachment were significantly associated with DSO symptoms but not with PTSD symptoms. Dismissing attachment style was significantly associated with PTSD and DSO symptoms. Preoccupied attachment was not significantly associated with CPTSD symptoms. Treatment implications for CPTSD using an attachment framework are discussed.

Published
2022

45. Natural diversity provides a broad spectrum of cyanobacteriochrome-based diguanylate cyclases

Author

Nathan C. Rockwell, Matthew Blain-Hartung, and J. Clark Lagarias

Subjects
Physiology, Regulator, Biosensing Techniques, Plant Science, Computational biology, Biology, Cyanobacteria, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Genetics, Bilin, 030304 developmental biology, 0303 health sciences, Phytochrome, Escherichia coli Proteins, 030302 biochemistry & molecular biology, Biofilm, Focus Issue on Sensors and Controllers, Tetrapyrrole, chemistry, Second messenger system, biology.protein, Diguanylate cyclase, Cyanobacteriochrome, Phosphorus-Oxygen Lyases
Abstract

Cyanobacteriochromes (CBCRs) are spectrally diverse photosensors from cyanobacteria distantly related to phytochromes that exploit photoisomerization of linear tetrapyrrole (bilin) chromophores to regulate associated signaling output domains. Unlike phytochromes, a single CBCR domain is sufficient for photoperception. CBCR domains that regulate the production or degradation of cyclic nucleotide second messengers are becoming increasingly well characterized. Cyclic di-guanosine monophosphate (c-di-GMP) is a widespread small-molecule regulator of bacterial motility, developmental transitions, and biofilm formation whose biosynthesis is regulated by CBCRs coupled to GGDEF (diguanylate cyclase) output domains. In this study, we compare the properties of diverse CBCR-GGDEF proteins with those of synthetic CBCR-GGDEF chimeras. Our investigation shows that natural diversity generates promising candidates for robust, broad spectrum optogenetic applications in live cells. Since light quality is constantly changing during plant development as upper leaves begin to shade lower leaves—affecting elongation growth, initiation of flowering, and responses to pathogens, these studies presage application of CBCR-GGDEF sensors to regulate orthogonal, c-di-GMP-regulated circuits in agronomically important plants for robust mitigation of such deleterious responses under natural growing conditions in the field.

Published
2021

46. Study Findings from Boston University Provide New Insights into Gene Therapy [Stimulation of Lateral Parabrachial (Lpb) To Central Amygdala (Cea) Pituitary Adenylate Cyclase-activating Polypeptide (Pacap) Neurons Induces Anxiety-like Behavior...].

Abstract

Keywords: Boston; State:Massachusetts; United States; North and Central America; Adenylate Cyclase; Amygdala; Anxiety; Anxiety Disorders; Basal Ganglia; Bioengineering; Biotechnology; Brain Research; Central Nervous System; Drugs and Therapies; Enzymes and Coenzymes; Gene Therapy; Health and Medicine; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Limbic System; Mental Health Diseases and Conditions; Nerve Growth Factors; Neurologic Manifestations; Neuropeptides; Pain; Phosphorus-Oxygen Lyases; Pituitary Adenylate Cyclase-Activating Polypeptide; Prosencephalon; Proteins; Telencephalon EN Boston State:Massachusetts United States North and Central America Adenylate Cyclase Amygdala Anxiety Anxiety Disorders Basal Ganglia Bioengineering Biotechnology Brain Research Central Nervous System Drugs and Therapies Enzymes and Coenzymes Gene Therapy Health and Medicine Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins Limbic System Mental Health Diseases and Conditions Nerve Growth Factors Neurologic Manifestations Neuropeptides Pain Phosphorus-Oxygen Lyases Pituitary Adenylate Cyclase-Activating Polypeptide Prosencephalon Proteins Telencephalon 2171 2171 1 09/25/23 20230929 NES 230929 2023 SEP 29 (NewsRx) -- By a News Reporter-Staff News Editor at Gene Therapy Weekly -- A new study on Biotechnology - Gene Therapy is now available. [Extracted from the article]

Published
2023

47. Researchers from University of Gothenburg Detail Findings in Guanylate Cyclase (Soluble guanylate cyclase mediates the relaxation of healthy and inflamed bladder smooth muscle by aqueous nitric oxide).

Abstract

Keywords: Chemicals; Cyclase; Enzymes and Coenzymes; Guanylate Cyclase; Health and Medicine; Inflammation; Intracellular Signaling Peptides and Proteins; Methacholine; Nitric Oxide; Nitrogen Oxides; Pharmaceuticals; Phosphorus-Oxygen Lyases; Reactive Nitrogen Species EN Chemicals Cyclase Enzymes and Coenzymes Guanylate Cyclase Health and Medicine Inflammation Intracellular Signaling Peptides and Proteins Methacholine Nitric Oxide Nitrogen Oxides Pharmaceuticals Phosphorus-Oxygen Lyases Reactive Nitrogen Species 1981 1981 1 09/19/23 20230922 NES 230922 2023 SEP 22 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Researchers detail new data in guanylate cyclase. For more information on this research see: Soluble guanylate cyclase mediates the relaxation of healthy and inflamed bladder smooth muscle by aqueous nitric oxide. [Extracted from the article]

Published
2023

48. Research on Glaucoma Reported by a Researcher at University of Pecs (Protective Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on Retinal Vasculature and Molecular Responses in a Rat Model of Moderate Glaucoma).

Subjects
PITUITARY adenylate cyclase activating polypeptide, NERVE tissue proteins, ANIMAL disease models, GLAUCOMA, OCULAR hypertension, BLOOD vessels
Abstract

Keywords: Adenylate Cyclase; Enzymes and Coenzymes; Eye Diseases and Conditions; Glaucoma; Health and Medicine; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Nerve Growth Factors; Neuropeptides; Phosphorus-Oxygen Lyases; Pituitary Adenylate Cyclase-Activating Polypeptide; Proteins; Risk and Prevention EN Adenylate Cyclase Enzymes and Coenzymes Eye Diseases and Conditions Glaucoma Health and Medicine Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins Nerve Growth Factors Neuropeptides Phosphorus-Oxygen Lyases Pituitary Adenylate Cyclase-Activating Polypeptide Proteins Risk and Prevention 995 995 1 09/11/23 20230911 NES 230911 2023 SEP 11 (NewsRx) -- By a News Reporter-Staff News Editor at Cardiovascular Week -- Investigators publish new report on glaucoma. Adenylate Cyclase, Enzymes and Coenzymes, Eye Diseases and Conditions, Glaucoma, Health and Medicine, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Nerve Growth Factors, Neuropeptides, Phosphorus-Oxygen Lyases, Pituitary Adenylate Cyclase-Activating Polypeptide, Proteins, Risk and Prevention. [Extracted from the article]

Published
2023

49. Studies from Normandie University Reveal New Findings on Nerve Growth Factors (The Heterogeneity of Response of Pc12 Cells From Different Laboratories To Nerve Growth Factor and Pituitary Adenylate Cyclase-activating Polypeptide Questions the...).

Abstract

France, Europe, Adenylate Cyclase, Rouen, Cell Research, Enzymes and Coenzymes, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Nerve Tissue Proteins, Neuropeptides, Phosphorus-Oxygen Lyases, Nerve Growth Factors, Pituitary Adenylate Cyclase-Activating Polypeptide, Proteins, Tumor Cell Line Keywords: Rouen; France; Europe; Adenylate Cyclase; Cell Research; Enzymes and Coenzymes; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Nerve Growth Factors; Nerve Tissue Proteins; Neuropeptides; Phosphorus-Oxygen Lyases; Pituitary Adenylate Cyclase-Activating Polypeptide; Proteins; Tumor Cell Line EN Rouen France Europe Adenylate Cyclase Cell Research Enzymes and Coenzymes Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins Nerve Growth Factors Nerve Tissue Proteins Neuropeptides Phosphorus-Oxygen Lyases Pituitary Adenylate Cyclase-Activating Polypeptide Proteins Tumor Cell Line 1516 1516 1 07/31/23 20230731 NES 230731 2023 AUG 4 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Fresh data on Intercellular Signaling Peptides and Proteins - Nerve Growth Factors are presented in a new report. [Extracted from the article]

Published
2023

50. Baker Heart and Diabetes Institute Researchers Illuminate Research in Diabetic Nephropathy (Ameliorating diabetes-associated atherosclerosis and diabetic nephropathy through modulation of soluble guanylate cyclase).

Abstract

Keywords: Arterial Occlusive Diseases; Arteriosclerosis; Atherosclerosis; Cardiovascular Diseases and Conditions; Cyclase; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathy; Enzymes and Coenzymes; Guanylate Cyclase; Health and Medicine; Inflammation; Intracellular Signaling Peptides and Proteins; Kidney; Kidney Diseases and Conditions; Nephrology; Nephropathy; Nitric Oxide; Nitrogen Oxides; Nutritional and Metabolic Diseases and Conditions; Phosphorus-Oxygen Lyases; Risk and Prevention EN Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases and Conditions Cyclase Diabetes Complications Diabetes Mellitus Diabetic Nephropathy Enzymes and Coenzymes Guanylate Cyclase Health and Medicine Inflammation Intracellular Signaling Peptides and Proteins Kidney Kidney Diseases and Conditions Nephrology Nephropathy Nitric Oxide Nitrogen Oxides Nutritional and Metabolic Diseases and Conditions Phosphorus-Oxygen Lyases Risk and Prevention 93 93 1 07/24/23 20230724 NES 230724 2023 JUL 24 (NewsRx) -- By a News Reporter-Staff News Editor at Diabetes Week -- Research findings on diabetic nephropathy are discussed in a new report. For more information on this research see: Ameliorating diabetes-associated atherosclerosis and diabetic nephropathy through modulation of soluble guanylate cyclase. [Extracted from the article]

Published
2023

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