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https://www.readbyqxmd.com/read/29923852/steroid-withdrawal-effects-following-long-term-topical-corticosteroid-use
#1
Belinda Sheary
BACKGROUND: Concerns about topical steroid withdrawal (TSW) are leading some patients to cease long-term topical corticosteroid (TCS) therapy. Diagnostic criteria for this condition do not exist. OBJECTIVE: The aim of this study was to examine the demographics and outcomes in adult patients who believe they are experiencing TSW following discontinuation of chronic TCS overuse. METHODS: This was a retrospective cohort study of patients in an Australian general practice presenting with this clinical scenario between January 2015 and February 2018...
June 19, 2018: Dermatitis
https://www.readbyqxmd.com/read/29887846/the-staphylococcus-aureus-two-component-system-agrac-displays-four-distinct-genomic-arrangements-that-delineate-genomic-virulence-factor-signatures
#2
Kumari S Choudhary, Nathan Mih, Jonathan Monk, Erol Kavvas, James T Yurkovich, George Sakoulas, Bernhard O Palsson
Two-component systems (TCSs) consist of a histidine kinase and a response regulator. Here, we evaluated the conservation of the AgrAC TCS among 149 completely sequenced Staphylococcus aureus strains. It is composed of four genes: agrBDCA . We found that: (i) AgrAC system ( agr ) was found in all but one of the 149 strains, (ii) the agr positive strains were further classified into four agr types based on AgrD protein sequences, (iii) the four agr types not only specified the chromosomal arrangement of the agr genes but also the sequence divergence of AgrC histidine kinase protein, which confers signal specificity, (iv) the sequence divergence was reflected in distinct structural properties especially in the transmembrane region and second extracellular binding domain, and (v) there was a strong correlation between the agr type and the virulence genomic profile of the organism...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29885211/the-role-of-two-component-systems-in-the-physiology-of-mycobacterium-tuberculosis
#3
REVIEW
Manikuntala Kundu
Tuberculosis is a global health problem, with a third of the world's population infected with the bacillus, Mycobacterium tuberculosis. The problem is exacerbated by the emergence of multidrug resistant and extensively drug resistant strains. The search for new drug targets is therefore a priority for researchers in the field. The two-component systems (TCSs) are central to the ability of the bacterium to sense and to respond appropriately to its environment. Here we summarize current knowledge on the paired TCSs of M...
June 9, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29880803/multiple-communication-mechanisms-between-sensor-kinases-are-crucial-for-virulence-in-pseudomonas-aeruginosa
#4
Vanessa I Francis, Elaine M Waters, Sutharsan E Finton-James, Andrea Gori, Aras Kadioglu, Alan R Brown, Steven L Porter
Bacteria and many non-metazoan Eukaryotes respond to stresses and threats using two-component systems (TCSs) comprising sensor kinases (SKs) and response regulators (RRs). Multikinase networks, where multiple SKs work together, detect and integrate different signals to control important lifestyle decisions such as sporulation and virulence. Here, we study interactions between two SKs from Pseudomonas aeruginosa, GacS and RetS, which control the switch between acute and chronic virulence. We demonstrate three mechanisms by which RetS attenuates GacS signalling: RetS takes phosphoryl groups from GacS-P; RetS has transmitter phosphatase activity against the receiver domain of GacS-P; and RetS inhibits GacS autophosphorylation...
June 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29865824/integral-elastic-vibrational-excitation-electronic-state-excitation-ionization-and-total-cross-sections-for-electron-scattering-from-para-benzoquinone
#5
D B Jones, R F da Costa, F Kossoski, M T do N Varella, M H F Bettega, G García, F Blanco, R D White, M A P Lima, M J Brunger
We report absolute experimental integral cross sections (ICSs) for the electron impact excitation of 6 bands (Bands 0-V) of unresolved electronic-states in para-benzoquinone, for incident electron energies between 20 and 40 eV. Absolute vibrational-excitation ICSs, for 3 composite vibrational bands (Bands I-III), are also reported in that same energy range. In addition, ICSs calculated within our independent atom model (IAM) with screening corrected additivity rule (SCAR) formalism, extended to account for interference (I) terms that arise due to the multi-centre nature of the scattering problem, are also reported...
May 28, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29789370/a-single-domain-response-regulator-functions-as-an-integrating-hub-to-coordinate-general-stress-response-and-development-in-alphaproteobacteria
#6
C Lori, A Kaczmarczyk, I de Jong, U Jenal
The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus , PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase...
May 22, 2018: MBio
https://www.readbyqxmd.com/read/29775128/long-term-serum-platinum-changes-and-their-association-with-cisplatin-related-late-effects-in-testicular-cancer-survivors
#7
Line V Hjelle, Per O M Gundersen, Ragnhild Hellesnes, Mette Sprauten, Marianne Brydøy, Torgrim Tandstad, Tom Wilsgaard, Sophie D Fosså, Jan Oldenburg, Roy M Bremnes, Hege S Haugnes
BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment...
May 18, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29769379/activation-of-bacterial-histidine-kinases-insights-into-the-kinetics-of-the-cis-autophosphorylation-mechanism
#8
Gaurav D Sankhe, Narendra M Dixit, Deepak K Saini
Two-component signaling systems (TCSs) are central to bacterial adaptation. However, the mechanisms underlying the reactions involving TCS proteins and their reaction rates are largely undetermined. Here, we employed a combined experimental and theoretical approach to elucidate the kinetics of autophosphorylation of three histidine kinases (HKs) of Mycobacterium tuberculosis , viz. , MtrB, PrrB, and PhoR, all known to play a role in regulating its virulence. Using wild-type and mutant proteins, we performed dimerization assays, thermophoretic-affinity measurements, and competition-based phosphorylation assays to establish that for HK, MtrB autophosphorylation occurs in cis , similar to what has been proposed for the PhoR and PrrB HKs...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29719540/a-novel-phop-phoq-regulation-pathway-modulates-the-survival-of-extraintestinal-pathogenic-escherichia-coli-in-macrophages
#9
Xiangkai Zhuge, Yu Sun, Feng Xue, Fang Tang, Jianluan Ren, Dezhi Li, Juanfang Wang, Min Jiang, Jianjun Dai
The extraintestinal pathogenic Escherichia coli (ExPEC) is a typical facultative intracellular bacterial pathogen. Sensing the environmental stimuli and undertaking adaptive change are crucial for ExPEC to successfully colonize in specific extraintestinal niches. The previous studies show that pathogens exploit two-component systems (TCSs) in response to the host environments during its infection. The PhoP/PhoQ is a typical TCS which is ubiquitous in Gram-negative bacteria. However, there is an incompletely understanding about critical regulatory roles of PhoP/PhoQ in ExPEC pathogenesis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29701037/-warming-acupuncture-combined-with-conventional-acupuncture-for-diabetic-peripheral-neuropathy-with-syndrome-of-yang-deficiency-and-cold-coagulation-obstruction-of-collaterals-and-blood-stasis
#10
Guoqing Ma, Ting Ye, Zhongren Sun
OBJECTIVE: To compare the clinical efficacy differences between warming acupuncture and conventional acupuncture for diabetic peripheral neuropathy (DPN) with syndrome of yang deficiency and cold coagulation, obstruction of collaterals and blood stasis. METHODS: A total of 64 patients were randomly divided into a warming acupuncture group and a conventional acupuncture group, 32 cases in each one. Based on basic treatment of blood glucose regulation, warming acupuncture was applied at Pishu (BL 20), Shenshu (BL 23), Guanyuanshu (BL 26), Zusanli (ST 36), Chongyang (ST 42), Quchi (LI 11) and Hegu (LI 4) in the warming acupuncture group, while acupuncture was applied at the identical acupoints in the conventional acupuncture group...
March 12, 2018: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29699476/an-improved-approach-to-infer-protein-protein-interaction-based-on-a-hierarchical-vector-space-model
#11
Jiongmin Zhang, Ke Jia, Jinmeng Jia, Ying Qian
BACKGROUND: Comparing and classifying functions of gene products are important in today's biomedical research. The semantic similarity derived from the Gene Ontology (GO) annotation has been regarded as one of the most widely used indicators for protein interaction. Among the various approaches proposed, those based on the vector space model are relatively simple, but their effectiveness is far from satisfying. RESULTS: We propose a Hierarchical Vector Space Model (HVSM) for computing semantic similarity between different genes or their products, which enhances the basic vector space model by introducing the relation between GO terms...
April 27, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29685990/the-two-component-signaling-system-vrasr-ss-is-critical-for-multidrug-resistance-and-full-virulence-in-streptococcus-suis-serotype-2
#12
Xiaojun Zhong, Yue Zhang, Yinchu Zhu, Wenyang Dong, Jiale Ma, Zihao Pan, Shipra Roy, Chengping Lu, Huochun Yao
Streptococcus suis has received increasing attention for its involvement in severe human infections worldwide, as well as in multidrug resistance. Two-component signaling systems (TCSSs) play important roles in bacterial adaptation to various environmental stimuli. In this study, we identified a novel TCSS encoded in S. suis serotype 2 (SS2), designated as VraSRSS , which is involved in bacterial pathogenicity and susceptibility to antimicrobials. Our data demonstrated that the yvqFSS gene located upstream of vraSRSS shared the same promoter with the TCSS genes, which was directly regulated by VraSRSS as showed in electrophoretic mobility shift assays...
April 23, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29662838/the-cpxa-cpxr-two-component-system-affects-biofilm-formation-and-virulence-in-actinobacillus-pleuropneumoniae
#13
Huan Li, Feng Liu, Wei Peng, Kang Yan, Haixu Zhao, Ting Liu, Hui Cheng, Peixi Chang, Fangyan Yuan, Huanchun Chen, Weicheng Bei
Gram-negative bacteria have evolved numerous two-component systems (TCSs) to cope with external environmental changes. The CpxA/CpxR TCS consisting of the kinase CpxA and the regulator CpxR, is known to be involved in the biofilm formation and virulence of Escherichia coli . However, the role of CpxA/CpxR remained unclear in Actinobacillus pleuropneumoniae , a bacterial pathogen that can cause porcine contagious pleuropneumonia (PCP). In this report, we show that CpxA/CpxR contributes to the biofilm formation ability of A...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29650958/phosphatase-activity-tunes-two-component-system-sensor-detection-threshold
#14
Brian P Landry, Rohan Palanki, Nikola Dyulgyarov, Lucas A Hartsough, Jeffrey J Tabor
Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways in biology, and a major source of sensors for biotechnology. However, the input concentrations to which biosensors respond are often mismatched with application requirements. Here, we utilize a mathematical model to show that TCS detection thresholds increase with the phosphatase activity of the sensor histidine kinase. We experimentally validate this result in engineered Bacillus subtilis nitrate and E. coli aspartate TCS sensors by tuning their detection threshold up to two orders of magnitude...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29563900/a-systematic-evaluation-of-the-two-component-systems-network-reveals-that-arlrs-is-a-key-regulator-of-catheter-colonization-by-staphylococcus-aureus
#15
Saioa Burgui, Carmen Gil, Cristina Solano, Iñigo Lasa, Jaione Valle
Two-component systems (TCS) are modular signal transduction pathways that allow cells to adapt to prevailing environmental conditions by modifying cellular physiology. Staphylococcus aureus has 16 TCSs to adapt to the diverse microenvironments encountered during its life cycle, including host tissues and implanted medical devices. S. aureus is particularly prone to cause infections associated to medical devices, whose surfaces coated by serum proteins constitute a particular environment. Identification of the TCSs involved in the adaptation of S...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29559812/a-cohort-study-on-the-risk-of-lymphoma-and-skin-cancer-in-users-of-topical-tacrolimus-pimecrolimus-and-corticosteroids-joint-european-longitudinal-lymphoma-and-skin-cancer-evaluation-joelle-study
#16
Jordi Castellsague, Josephina G Kuiper, Anton Pottegård, Ingegärd Anveden Berglind, Daniel Dedman, Lia Gutierrez, Brian Calingaert, Myrthe Pp van Herk-Sukel, Jesper Hallas, Anders Sundström, Arlene M Gallagher, James A Kaye, Carolina Pardo, Kenneth J Rothman, Susana Perez-Gutthann
Background: There is a concern that topical tacrolimus and pimecrolimus, indicated for second-line treatment of atopic dermatitis, may increase the risk of lymphoma and skin cancer, particularly in children. Objective: The aim of this study was to compare incidence rates (IRs) of lymphoma and skin cancer between new users of topical tacrolimus or pimecrolimus and users of moderate- to high-potency topical corticosteroids (TCSs) and untreated subjects. Methods: This is a multicenter cohort study with frequency matching by strata of propensity scores in population databases in the Netherlands, Denmark, Sweden, and the UK...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29543889/spdc-a-novel-virulence-factor-controls-histidine-kinase-activity-in-staphylococcus-aureus
#17
Olivier Poupel, Caroline Proux, Bernd Jagla, Tarek Msadek, Sarah Dubrac
The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt to a wide spectrum of environmental conditions. Two-component systems (TCSs) play a crucial role in this process. Here, we describe a novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved in signal sensing and/or transduction. We have uncovered a functional link between the WalKR essential TCS and the SpdC Abi membrane protein. Expression of spdC is positively regulated by the WalKR system and, in turn, SpdC negatively controls WalKR regulon genes, effectively constituting a negative feedback loop...
March 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29534941/predicting-cardiovascular-disease-among-testicular-cancer-survivors-after-modern-cisplatin-based-chemotherapy-application-of-the-framingham-risk-score
#18
Darren R Feldman, Shirin Ardeshir-Rouhani-Fard, Patrick Monahan, Howard D Sesso, Chunkit Fung, Annalynn M Williams, Robert J Hamilton, David J Vaughn, Clair J Beard, Ryan Cook, Mohammad Abu Zaid, Steven E Lipshultz, Lawrence H Einhorn, Kevin C Oeffinger, Lois B Travis, Sophie D Fossa
BACKGROUND: Testicular cancer survivors (TCSs) are at increased risk of cardiovascular disease (CVD) after cisplatin-based chemotherapy (CBCT). Identifying at-risk survivors would allow early intervention, but risk prediction tools such as the Framingham Risk Score (FRS) have not been applied to TCSs given modern chemotherapy. METHODS: TCSs > 1 year post-CBCT were evaluated. Associations between FRS and clinical, socioeconomic, and lifestyle measures and treatment regimen (4 cycles, etoposide and cisplatin [EP × 4]); 3 or 4 cycles, bleomycin plus EP (BEP × 3, BEP × 4) were analyzed with general linear multivariable models...
February 5, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29515973/cohort-profile-the-danish-testicular-cancer-late-treatment-effects-cohort-dateca-late
#19
Michael Kreiberg, Mikkel Bandak, Jakob Lauritsen, Julie Wang Skøtt, Nanna Borup Johansen, Mads Agerbaek, Niels Vilstrup Holm, Christoffer Johansen, Gedske Daugaard
The cohort was set up in order to analyze late effects in long-term testicular cancer survivors (TCS) and to contribute to the design of future follow-up programs addressing and potentially preventing late effects. Data for this cross-sectional study were collected between January 1, 2014, and December 31, 2016, among living Danish TCS and 60% agreed to participate in the cohort ( N  = 2,572). Mean time since testicular cancer (TC) diagnosis was 18 years (range 7-33) and mean age of participants was 53 years (range 25-95)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29487854/re-sensitizing-multidrug-resistant-bacteria-to-antibiotics-by-targeting-bacterial-response-regulators-characterization-and-comparison-of-interactions-between-2-aminoimidazoles-and-the-response-regulators-bfmr-from-acinetobacter-baumannii-and-qseb-from-francisella
#20
Morgan E Milton, Bradley M Minrovic, Danni L Harris, Brian Kang, David Jung, Caleb P Lewis, Richele J Thompson, Roberta J Melander, Daina Zeng, Christian Melander, John Cavanagh
2-aminoimidazole (2-AI) compounds inhibit the formation of bacterial biofilms, disperse preformed biofilms, and re-sensitize multidrug resistant bacteria to antibiotics. 2-AIs have previously been shown to interact with bacterial response regulators, but the mechanism of interaction is still unknown. Response regulators are one part of two-component systems (TCS). TCSs allow cells to respond to changes in their environment, and are used to trigger quorum sensing, virulence factors, and antibiotic resistance...
2018: Frontiers in Molecular Biosciences
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