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Carolin Schneider, James H W LaFortune, Rebecca L Melen, Douglas W Stephan
The compounds EtOC([double bond, length as m-dash]O)CHNNPR3 (R = Ph 1, Cy 2, tBu 3) were prepared via the reactions of the diazomethane and a phosphine. In subsequent reactions with B(C6F5)3, the compounds 2 and 3 are shown to exhibit Lewis basicity at the carbonyl oxygen affording EtOC([double bond, length as m-dash]O(B(C6F5)3))CHNNPR3 (R = Cy 5, tBu 6). Reactions of 5 and 6 with water or phenol illustrated the Brønsted basicity at the nitrogen atom adjacent phosphorus, affording the compounds, [EtOC([double bond, length as m-dash]O)CHNNHPR3][HOB(C6F5)3] (R = Cy 7, tBu 8) and [EtOC([double bond, length as m-dash]O)CHNNHPR3][PhOB(C6F5)3] (R = Cy 9, tBu 10), respectively...
September 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Sabrina Ehnert, Caren Linnemann, Romina H Aspera-Werz, Daria Bykova, Sara Biermann, Leonie Fecht, Peter M De Zwart, Andreas K Nussler, Fabian Stuby
The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 ( NOX4 ) and focal adhesion kinase (FAK) as possible regulators...
July 31, 2018: International Journal of Molecular Sciences
Phob Ganokroj, Pisit Lertwanich
A groin mass is an unusual presentation of hip-related problems. Paralabral cysts are common radiographic findings that are often associated with intraarticular pathology. The authors describe a 57-year-old woman who presented with a left groin mass for 6 months. Magnetic resonance imaging showed an acetabular paralabral cyst at the anterior aspect of the hip joint. Arthroscopic paralabral cyst decompression was performed. An associated degenerative anterosuperior labrum and partial tear of the ligamentum teres were also identified and treated with arthroscopic debridement...
September 1, 2018: Orthopedics
Issam Hamdallah, Nadia Torok, Katarina M Bischof, Nadim Majdalani, Sriya Chadalavada, Nonto Mdluli, Kaitlin E Creamer, Michelle Clark, Chase Holdener, Preston J Basting, Susan Gottesman, Joan L Slonczewski
Experimental evolution of Escherichia coli K-12 W3110 by serial dilutions for 2,200 generations at high pH extended the range of sustained growth from pH 9.0 to pH 9.3. pH 9.3-adapted isolates showed mutations in DNA-binding regulators and envelope proteins. One population showed an IS 1 knockout of phoB (encoding the positive regulator of the phosphate regulon). A phoB :: kanR knockout increased growth at high pH. phoB mutants are known to increase production of fermentation acids, which could enhance fitness at high pH...
August 1, 2018: Applied and Environmental Microbiology
Julie L Stoudenmire, Tara Essock-Burns, Erena N Weathers, Sina Solaimanpour, Jan Mrázek, Eric V Stabb
Transcriptional reporters are common tools for analyzing either the transcription of a gene of interest or the activity of a specific transcriptional regulator. Unfortunately, the latter application has the shortcoming that native promoters did not evolve as optimal readouts for the activity of a particular regulator. We sought to synthesize an optimized transcriptional reporter for assessing PhoB activity, aiming for maximal "on" expression when PhoB is active, minimal background in the "off" state, and no control elements for other regulators...
May 11, 2018: Applied and Environmental Microbiology
Xinhui Kou, Yixiang Liu, Conggang Li, Maili Liu, Ling Jiang
PhoB is a response regulator of PhoR/PhoB two-component system from Escherichia coli that is involved in the environmental phosphate regulation. It has been reported that the N-terminal receiver domain (PhoBN ) forms a dimer using the α1-α5 face in the apo state and a dimer using the α4-β5-α5 face in the active state investigated by X-ray crystallography. However, it is not clear whether the conformational switch of the dimer is dependent on phosphorylation. Here, we report the NMR studies of PhoBN in solution in its apo form...
June 7, 2018: Journal of Physical Chemistry. B
Sajjad Ahmad, Saad Raza, Reaz Uddin, Syed Sikander Azam
Multidrug-resistant Acinetobacter baumannii is indeed to be the most successful nosocomial pathogen responsible for myriad infections in modern health care system. Computational methodologies based on genomics and proteomics proved to be powerful tools for providing substantial information about different aspects of A. baumannii biology that made it possible to design new approaches for treating multi, extensive and total drug resistant isolates of A. baumannii. In this current approach, 35 completely annotated proteomes of A...
June 2018: Journal of Molecular Graphics & Modelling
Jiezhang Jiang, Kaiwen Yu, Linlu Qi, Yanhua Liu, Sen Cheng, Mei Wu, Zhen Wang, Jiaqi Fu, Xiaoyun Liu
Salmonella enterica serovar Typhimurium ( S. Typhimurium), an important foodborne pathogen, often encounters phosphate (Pi ) shortage both in the environment and inside host cells. To gain a global view on its physiological responses to Pi starvation, we performed proteomic profiling of S. Typhimurium upon the shift from Pi -rich to Pi -low conditions. In addition to the Pho regulon, many metabolic processes were up-regulated, such as glycolysis, pentose phosphate pathway, pyrimidine degradation, glycogen, and trehalose metabolism, allowing us to chart an overview of S...
April 25, 2018: Proteomes
Yue Hu, Jian Jiao, Li Xue Liu, Yan Wei Sun, Wen Feng Chen, Xin Hua Sui, Wen Xin Chen, Chang Fu Tian
Phosphate homeostasis is tightly modulated in all organisms, including bacteria, which harbor both high- and low-affinity transporters acting under conditions of fluctuating phosphate levels. It was thought that nitrogen-fixing rhizobia, named bacteroids, inhabiting root nodules of legumes are not phosphate limited. Here, we show that the high-affinity phosphate transporter PstSCAB, rather than the low-affinity phosphate transporter Pit, is essential for effective nitrogen fixation of Sinorhizobium fredii in soybean nodules...
October 2018: Molecular Plant-microbe Interactions: MPMI
G Logan Draughn, Morgan E Milton, Erik A Feldmann, Benjamin G Bobay, Braden M Roth, Andrew L Olson, Richele J Thompson, Luis A Actis, Christopher Davies, John Cavanagh
The rise of drug-resistant bacterial infections coupled with decreasing antibiotic efficacy poses a significant challenge to global health care. Acinetobacter baumannii is an insidious, emerging bacterial pathogen responsible for severe nosocomial infections aided by its ability to form biofilms. The response regulator BfmR, from the BfmR/S two-component system, is the master regulator of biofilm initiation in A. baumannii and is a tractable therapeutic target. Here we present the structure of A. baumannii BfmR using a hybrid approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy, chemical crosslinking mass spectrometry, and molecular modeling...
March 16, 2018: Journal of Molecular Biology
F Failamani, R Podloucky, J Bursik, G Rogl, H Michor, H Müller, E Bauer, G Giester, P Rogl
The crystal structures of two novel borides in the Ni-Zn-B system, τ5 -Ni3 Zn2 B and τ6 -Ni2 ZnB, were determined by single crystal X-ray diffraction (XRSC) in combination with selected area electron diffraction in a transmission electron microscope (SAED-TEM) and electron probe microanalysis (EPMA). Both compounds crystallize in unique structure types (space group C2/m, a = 1.68942(8) nm, b = 0.26332(1) nm, c = 0.61904(3) nm, β = 111.164(2)°, RF = 0.0219 for Ni3 Zn2 B, and space group C2/m, a = 0.95296(7) nm, b = 0...
March 6, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Ramesh K Vuppada, Colby R Hansen, Kirsta A P Strickland, Keilen M Kelly, William R McCleary
BACKGROUND: Phosphate is an essential compound for life. Escherichia coli employs a signal transduction pathway that controls the expression of genes that are required for the high-affinity acquisition of phosphate and the utilization of alternate sources of phosphorous. These genes are only expressed when environmental phosphate is limiting. The seven genes for this signaling pathway encode the two-component regulatory proteins PhoB and PhoR, as well as the high-affinity phosphate transporter PstSCAB and an auxiliary protein called PhoU...
January 19, 2018: BMC Microbiology
Xinhui Kou, Xinghong Liu, Yixiang Liu, Conggang Li, Maili Liu, Ling Jiang
PhoB is a response regulator of the PhoR/PhoB two-component signal transduction system that is involved in the regulation of the phosphate (Pho) regulon of Escherichia coli. PhoB has two domains, receiver domain and effector domain. The receiver domain can be phosphorylated by its cognate histidine kinase PhoR and the phosphorylation induces conformational changes of the full length protein of PhoB that promote the DNA binding and transcription. Three-dimensional crystal structures of PhoB receiver domain (PhoBN ) have been solved under apo or BeF3 - (a phosphoryl analog) binding forms and it has been found that PhoBN is dimerized in both situations...
April 2018: Biomolecular NMR Assignments
Yumi Iwadate, Jun-Ichi Kato
The Escherichia coli PhoB-PhoR two-component system responds to phosphate starvation and induces the expression of many genes. Previous studies suggested that phosphate starvation induces oxidative stress, but the involvement of the PhoB regulon in oxidative stress tolerance has not been clarified. Here, we showed that ytfK, one of the PhoB regulon genes, is involved in cell tolerance to a redox-cycling drug, menadione, and H2O2 in stationary-phase cells. A ytfK deletion mutant was sensitive to H2O2 when the cells were grown anaerobically or micro-aerobically in the presence of nitrate...
December 2017: Microbiology
Jie Tan, Georgia Doing, Kimberley A Lewis, Courtney E Price, Kathleen M Chen, Kyle C Cady, Barret Perchuk, Michael T Laub, Deborah A Hogan, Casey S Greene
Cross-experiment comparisons in public data compendia are challenged by unmatched conditions and technical noise. The ADAGE method, which performs unsupervised integration with denoising autoencoder neural networks, can identify biological patterns, but because ADAGE models, like many neural networks, are over-parameterized, different ADAGE models perform equally well. To enhance model robustness and better build signatures consistent with biological pathways, we developed an ensemble ADAGE (eADAGE) that integrated stable signatures across models...
July 26, 2017: Cell Systems
Sarah B Namugenyi, Alisha M Aagesen, Sarah R Elliott, Anna D Tischler
The Mycobacterium tuberculosis phosphate-specific transport (Pst) system controls gene expression in response to phosphate availability by inhibiting the activation of the SenX3-RegX3 two-component system under phosphate-rich conditions, but the mechanism of communication between these systems is unknown. In Escherichia coli , inhibition of the two-component system PhoR-PhoB under phosphate-rich conditions requires both the Pst system and PhoU, a putative adaptor protein. E. coli PhoU is also involved in the formation of persisters, a subpopulation of phenotypically antibiotic-tolerant bacteria...
July 11, 2017: MBio
Rong Gao, Katherine A Godfrey, Mahir A Sufian, Ann M Stock
Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis...
September 15, 2017: Journal of Bacteriology
Rong Gao, Ann M Stock
Cells rely on accurate control of signaling systems to adapt to environmental perturbations. System deactivation upon stimulus removal is as important as activation of signaling pathways. The two-component system (TCS) is one of the major bacterial signaling schemes. In many TCSs, phosphatase activity of the histidine kinase (HK) is believed to play an essential role in shutting off the pathway and resetting the system to the prestimulus state. Two basic challenges are to understand the dynamic behavior of system deactivation and to quantitatively evaluate the role of phosphatase activity under natural cellular conditions...
May 16, 2017: MBio
George C diCenzo, Harsh Sharthiya, Anish Nanda, Maryam Zamani, Turlough M Finan
Maintenance of cellular phosphate homeostasis is essential for cellular life. The PhoU protein has emerged as a key regulator of this process in bacteria, and it is suggested to modulate phosphate import by PstSCAB and control activation of the phosphate limitation response by the PhoR-PhoB two-component system. However, a proper understanding of PhoU has remained elusive due to numerous complications of mutating phoU , including loss of viability and the genetic instability of the mutants. Here, we developed two sets of strains of Sinorhizobium meliloti that overcame these limitations and allowed a more detailed and comprehensive analysis of the biological and molecular activities of PhoU...
September 15, 2017: Journal of Bacteriology
Nicola Horstmann, Pranoti Sahasrabhojane, Hui Yao, Xiaoping Su, Samuel A Shelburne
Control of the virulence regulator/sensor kinase (CovRS) two-component system (TCS) serves as a model for investigating the impact of signaling pathways on the pathogenesis of Gram-positive bacteria. However, the molecular mechanisms by which CovR, an OmpR/PhoB family response regulator, controls virulence gene expression are poorly defined, partly due to the labile nature of its aspartate phosphorylation site. To better understand the regulatory effect of phosphorylated CovR, we generated the phosphorylation site mutant strain 10870-CovR-D53E, which we predicted to have a constitutive CovR phosphorylation phenotype...
September 15, 2017: Journal of Bacteriology
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