scholarly journals Somatic mosaic truncating mutations of PPM1D in blood can result from expansion of a mutant clone under selective pressure of chemotherapy

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0217521 ◽  
Author(s):  
Borahm Kim ◽  
Dongju Won ◽  
Seung-Tae Lee ◽  
Jong Rak Choi
Keyword(s):  
Selective Pressure ◽  
Mutant Clone

scholarly journals Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarah A. Carratt ◽  
Diana Brewer ◽  
Julia E. Maxson ◽  
Brian J. Druker ◽  
Theodore P. Braun
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Complex Disease ◽  
Selective Pressure ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Hematologic Toxicity ◽  
Mutant Clone

Abstract Background Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling. Case presentation Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient’s clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient. Conclusions This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.

Study of Alnus incana L. Moench fruit extract biologically active substances influence on resistance development in mls-resistant staphylococci skin isolates

2018 ◽  
Vol 22 (2) ◽  
pp. 263-266
Author(s):  
R.V. Kutsyk ◽  
O.I. Yurchyshyn
Keyword(s):  
Selective Pressure ◽  
Biological Response ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Alnus Incana ◽  
Fruit Extract ◽  
Antimicrobial Drugs ◽  
Resistance Development ◽  
Subinhibitory Concentrations ◽  
Active Substances

The emergence of microorganisms resistant strains is a natural biological response to the use of antimicrobial drugs that creates selective pressure, contributing to pathogens selection, survival and reproduction. The purpose of the investigation was to study the resistance development of staphylococci skin isolates to erythromycin and influence on it Alnus incana L. fruit extract subinhibitory concentrations. Development of resistance to erythromycin and influence on it Alnus incana L. fruit extract (extraction by 90% ethanol) subinhibitory concentrations were conducted with S epidermidis strains: sensitive and resistant to 14 and 15-membered macrolides. The study was carried out within 30 days by multiple consecutive passages of staphylococci test strains (concentration 1×107 CFU/ml) into test tubes containing broth and erythromycin ranging from 3 doubling dilutions above to doubling dilutions below the minimum inhibitory concentration. Statistical analysis of the results was carried out by one-and two-factor analysis of variance (ANOVA) and Microsoft Office Excel 2011. Rapid increase of resistance from 32 to 1024 μg/ml (F=34.2804; F> Fstand. max = 5.9874; p=0.0011) for S.epidermidis with a low level of resistance to 14 and 15-membered macrolides resistance to the erythromycine was observed. In the presence of Alnus incana L. fruit extract subinhibitory concentrations (¼ MIC), the initial MIC of erythromycin was decreased by 32 times to 1 μg/ml (F = 9.7497; F> Fstand. max = 5.9874; p = 0.0205). The sensitive strain after 30 passages did not develop resistance to erythromycin. Under the influence of erythromycin selective pressure, S.epidermidis strain with low initial level of MLS-resistance rapidly reaches a high-level resistance. Biologically active substances of the Alnus incana L. fruit extract significantly inhibit the resistance development in S. epidermidis to macrolides and eliminate it phenotypic features.

Evolution, natural history, and conservation of black-footed ferrets

2018 ◽  
Author(s):  
Dean E. Biggins ◽  
David A. Eads
Keyword(s):  
Natural History ◽  
Captive Breeding ◽  
Alpine Meadow ◽  
Selective Pressure ◽  
Canine Distemper ◽  
Prairie Dog ◽  
Management Tools ◽  
Diverse Area ◽  
Close Relatives ◽  
Remnant Population

Black-footed ferrets were reduced to a remnant population of 10 in 1985 due to diseases (plague, canine distemper), but successful captive breeding and releases have improved the prospects for ferret recovery. Comparisons between black-footed ferrets and Siberian polecats, close relatives that can interbreed and produce fertile offspring, allow the following evolutionary speculation. Predation on ferrets and polecats tends to narrow their niches and promote specialization due to requirements for escape habitats. In Asia, that influence is countered by the larger and more diverse area of steppe and alpine meadow habitats for polecats, and by plague which causes large variation in prey abundance. In North America, the selective pressure favoring specialization in ferrets on prairie dog prey and burrows had no strong counter-force before plague invaded. Plague is an immense challenge to black-footed ferret recovery, and several management tools including vaccines and vector control may be necessary to conserve the species.

scholarly journals HLA and Infectious Diseases

2009 ◽  
Vol 22 (2) ◽  
pp. 370-385 ◽  
Author(s):  
Jenefer M. Blackwell ◽  
Sarra E. Jamieson ◽  
David Burgner
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Human Leukocyte Antigen ◽  
Molecular Basis ◽  
Selective Pressure ◽  
Human Leukocyte ◽  
Acquired Immunity ◽  
Leukocyte Antigen ◽  
Extreme Variability ◽  
Classical Human Leukocyte Antigen

SUMMARY Following their discovery in the early 1970s, classical human leukocyte antigen (HLA) loci have been the prototypical candidates for genetic susceptibility to infectious disease. Indeed, the original hypothesis for the extreme variability observed at HLA loci (H-2 in mice) was the major selective pressure from infectious diseases. Now that both the human genome and the molecular basis of innate and acquired immunity are understood in greater detail, do the classical HLA loci still stand out as major genes that determine susceptibility to infectious disease? This review looks afresh at the evidence supporting a role for classical HLA loci in susceptibility to infectious disease, examines the limitations of data reported to date, and discusses current advances in methodology and technology that will potentially lead to greater understanding of their role in infectious diseases in the future.

scholarly journals Selective Pressure of Antibiotic Pollution on Bacteria of Importance to Public Health

2012 ◽  
Vol 120 (8) ◽  
pp. 1100-1106 ◽  
Author(s):  
Alfredo Tello ◽  
Brian Austin ◽  
Trevor C Telfer
Keyword(s):  
Public Health ◽  
Selective Pressure

scholarly journals Specific phenotypic, genomic, and fitness evolutionary trajectories toward streptomycin resistance induced by pesticide co-stressors in Escherichia coli

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Yue Xing ◽  
Xiaoxi Kang ◽  
Siwei Zhang ◽  
Yujie Men
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Selective Pressure ◽  
Fold Increase ◽  
Streptomycin Resistance ◽  
Evolutionary Stage ◽  
Fitness Costs ◽  
Evolutionary Trajectories ◽  
K 12 ◽  
Late Stages

AbstractTo explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolutionary trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5–6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.

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