scholarly journals Novel mutator mutants of E. coli nrdAB ribonucleotide reductase: Insight into allosteric regulation and control of mutation rates

DNA Repair ◽  
2012 ◽  
Vol 11 (5) ◽  
pp. 480-487 ◽  
Author(s):  
Deepti Ahluwalia ◽  
Rachelle J. Bienstock ◽  
Roel M. Schaaper
2020 ◽  
Vol 295 (46) ◽  
pp. 15576-15587
Author(s):  
Markel Martínez-Carranza ◽  
Venkateswara Rao Jonna ◽  
Daniel Lundin ◽  
Margareta Sahlin ◽  
Lars-Anders Carlson ◽  
...  

Ribonucleotide reductase (RNR) is a central enzyme for the synthesis of DNA building blocks. Most aerobic organisms, including nearly all eukaryotes, have class I RNRs consisting of R1 and R2 subunits. The catalytic R1 subunit contains an overall activity site that can allosterically turn the enzyme on or off by the binding of ATP or dATP, respectively. The mechanism behind the ability to turn the enzyme off via the R1 subunit involves the formation of different types of R1 oligomers in most studied species and R1–R2 octamers in Escherichia coli. To better understand the distribution of different oligomerization mechanisms, we characterized the enzyme from Clostridium botulinum, which belongs to a subclass of class I RNRs not studied before. The recombinantly expressed enzyme was analyzed by size-exclusion chromatography, gas-phase electrophoretic mobility macromolecular analysis, EM, X-ray crystallography, and enzyme assays. Interestingly, it shares the ability of the E. coli RNR to form inhibited R1–R2 octamers in the presence of dATP but, unlike the E. coli enzyme, cannot be turned off by combinations of ATP and dGTP/dTTP. A phylogenetic analysis of class I RNRs suggests that activity regulation is not ancestral but was gained after the first subclasses diverged and that RNR subclasses with inhibition mechanisms involving R1 oligomerization belong to a clade separated from the two subclasses forming R1–R2 octamers. These results give further insight into activity regulation in class I RNRs as an evolutionarily dynamic process.


Author(s):  
Tamara Green

Much of the literature, policies, programs, and investment has been made on mental health, case management, and suicide prevention of veterans. The Australian “veteran community is facing a suicide epidemic for the reasons that are extremely complex and beyond the scope of those currently dealing with them.” (Menz, D: 2019). Only limited work has considered the digital transformation of loosely and manual-based historical records and no enablement of Artificial Intelligence (A.I) and machine learning to suicide risk prediction and control for serving military members and veterans to date. This paper presents issues and challenges in suicide prevention and management of veterans, from the standing of policymakers to stakeholders, campaigners of veteran suicide prevention, science and big data, and an opportunity for the digital transformation of case management.


1997 ◽  
Vol 35 (11-12) ◽  
pp. 35-40 ◽  
Author(s):  
B. Genthe ◽  
N. Strauss ◽  
J. Seager ◽  
C. Vundule ◽  
F. Maforah ◽  
...  

Efforts to provide water to developing communities in South Africa have resulted in various types of water supplies being used. This study examined the relationship between the type of water supply and the quality of water used. Source (communal taps, private outdoor and indoor taps) and point-of-use water samples were examined for heterotrophic plate counts (HPC), total and faecal coliforms, E. coli, and coliphages. Ten percent of samples were also analysed for enteric viruses, Giardia and Cryptosporidium. Approximately 320 households were included in a case-control study. In addition, a cross-sectional study was conducted. Both studies examined the relationship between different types of water facilities and diarrhoea among pre-school children. The source water was of good microbial quality, but water quality was found to have deteriorated significantly after handling and storage in both case and control households, exceeding drinking water quality guideline values by 1-6 orders of magnitude. Coliphage counts were low for all water samples tested. Enteric viruses and Cryptosporidium oocysts were not detected. Giardia cysts were detected on one occasion in case and control in-house samples. Comparisons of whether in-house water, after handling and storage, complied with water quality guideline values demonstrated households using communal taps to have significantly poorer quality than households using private outdoor or indoor taps for HPC and E. coli (χ2 = 14.9, P = 0.001; χ2 = 6.6, P = 0.04 respectively). A similar trend (although not statistically significant) was observed for the other microbial indicators. The cross-sectional study demonstrated an apparent decrease in health risk associated with private outdoor taps in comparison to communal taps. This study suggests that a private outdoor tap is the minimum level of water supply in order to ensure the supply of safe water to developing communities.


Author(s):  
David D. Nolte

Galileo Unbound: A Path Across Life, The Universe and Everything traces the journey that brought us from Galileo’s law of free fall to today’s geneticists measuring evolutionary drift, entangled quantum particles moving among many worlds, and our lives as trajectories traversing a health space with thousands of dimensions. Remarkably, common themes persist that predict the evolution of species as readily as the orbits of planets or the collapse of stars into black holes. This book tells the history of spaces of expanding dimension and increasing abstraction and how they continue today to give new insight into the physics of complex systems. Galileo published the first modern law of motion, the Law of Fall, that was ideal and simple, laying the foundation upon which Newton built the first theory of dynamics. Early in the twentieth century, geometry became the cause of motion rather than the result when Einstein envisioned the fabric of space-time warped by mass and energy, forcing light rays to bend past the Sun. Possibly more radical was Feynman’s dilemma of quantum particles taking all paths at once—setting the stage for the modern fields of quantum field theory and quantum computing. Yet as concepts of motion have evolved, one thing has remained constant, the need to track ever more complex changes and to capture their essence, to find patterns in the chaos as we try to predict and control our world.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Chibuzor M. Nsofor ◽  
Mirabeau Y. Tattfeng ◽  
Chijioke A. Nsofor

Abstract Background This study was aimed to determine the prevalence of qnr genes among fluoroquinolone-resistant Escherichia coli (FREC) isolates from Nigeria. Antimicrobial susceptibility testing was performed by disc diffusion technique. Polymerase chain reaction was used to identify Escherichia coli (E. coli) and for the detection of qnr genes. Results A total of 206 non-duplicate E. coli were isolated from 300 clinical specimens analyzed. In all, 30 (14.6%) of these isolates were FREC; the resistance to fluoroquinolones among these 30 FREC showed 80% (24), 86.7% (26), 86.7% (26), 100% (30), 86.7% (26), 93.3% (28) and 86.7% (26) were resistant to pefloxacin, ciprofloxacin, sparfloxacin, levofloxacin, nalidixic acid, ofloxacin and moxifloxacin, respectively. The distribution of FREC among the various sample sources analyzed showed that 14%, 10%, 13.3%, 16.7% and 20% of the isolates came from urine, stool, high vaginal swab, endo cervical swab and wound swab specimens, respectively. More FREC were isolated from female samples 73.3% (22) compared to male samples 26.7% (8) and were more prevalent among the age group 26–35 years (40%). Twenty eight out of the 30 (93.3%) FREC isolates possessed at least one fluoroquinolone resistance gene in the form of qnrA 10 (33.3%) and qnrB 18 (60%), respectively; qnrS was not detected among the FREC isolates analyzed and 13.5% of the isolates possessed both the qnrA and qnrB genes. Phylogenetic analysis showed that these isolates were genetically diverse. Conclusions These findings suggest a possible resistance to fluoroquinolone is of high interest for better management of patients and control of antimicrobial resistance in Nigeria.


2009 ◽  
Vol 89 (2) ◽  
pp. 285-293 ◽  
Author(s):  
S J Bach ◽  
R P Johnson ◽  
K. Stanford ◽  
T A McAllister

Bacteriophage biocontrol has potential as a means of mitigating the prevalence of Escherichia coli O157:H7 in ruminants. The efficacy of oral administration of bacteriophages for reducing fecal shedding of E. coli O157:H7 by sheep was evaluated using 20 Canadian Arcott rams (50.0 ± 3.0) housed in four rooms (n = 5) in a contained facility. The rams had ad libitum access to drinking water and a pelleted barley-based total mixed ration, delivered once daily. Experimental treatments consisted of administration of E. coli O157:H7 (O157), E. coli O157:H7+bacteriophages (O157+phage), bacteriophages (phage), and control (CON). Oral inoculation of the rams with 109 CFU of a mixture of four nalidixic acid-resistant strains of E. coli O157:H7 was performed on day 0. A mixture of 1010 PFU of bacteriophages P5, P8 and P11 was administered on days -2, -1, 0, 6 and 7. Fecal samples collected on 14 occasions over 21 d were analyzed for E. coli O157:H7, total E. coli, total coliforms and bacteriophages. Sheep in treatment O157+phage shed fewer (P < 0.05) E. coli O157:H7 than did sheep in treatment O157. Populations of total coliforms and total E. coli were similar (P < 0.05) among treatments, implying that bacteriophage lysis of non-target E. coli and coliform bacteria in the gastrointestinal tract did not occur. Bacteriophage numbers declined rapidly over 21 d, which likely reduced the chance of collision between bacteria and bacteriophage. Oral administration of bacteriophages reduced shedding of E. coli O157:H7 by sheep, but a delivery system that would protect bacteriophages during passage through the intestine may increase the effectiveness of this strategy as well as allow phage to be administered in the feed.Key words: Escherichia coli O157:H7, bacteriophage, sheep, environment, coliforms


Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Shomeek Chowdhury ◽  
Stephen Hepper ◽  
Mudassir K. Lodi ◽  
Milton H. Saier ◽  
Peter Uetz

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.


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