Level of mutation of the VKORC1 resistance gene to anticoagulants in house mice and norway rats in Moscow and Moscow region

2021 ◽  
pp. 55-62
Author(s):  
Aleksey Nikolaevich Maltsev ◽  
◽  
Elena Vladimirovna Kotenkova ◽  
Sergey Vasilevich Ryabov ◽  
Tatyana Viktorovna Gololobova ◽  
...  
Keyword(s):  
First Generation ◽  
Genetic Resistance ◽  
Resistance Mutation ◽  
Moscow Region ◽  
House Mice ◽  
Heterozygous State ◽  
2Nd Generation ◽  
Exon 1 ◽  
Norway Rats ◽  
Vkorc1 Gene

The resistance of house mice (M. musuclus linnaeus, 1758) and norway rats (R. norvegicus berkenhout, 1769) to anticoagulants of the 1st and 2nd generation in the VKORC1 gene in Moscow and the Moscow region was studied. House mice had two previously unknown mutations in exon 1: Lys175Arg и Ser94Trp. We assume that these mutations can increase the resistance of rodents to second-generation anticoagulants. the percentage of individuals with mutations in exon 1 in Moscow is 87.5 %, in Noginsk and Podolsk – 100 %. Of the 18 norway rats studied in Moscow, only three individuals in a heterozygous state were found to have one of the mutations (Tyr139Ser), usually associated with genetic resistance of rodents to the first generation anticoagulant warfarin. the percentage of resistant individuals in Moscow was 15.7 %. the rats in which the resistance mutation was found were captured in three districts of moscow: southwestern, northern and eastern.

scholarly journals Non-Small-Cell Lung Cancer-Sensitive Detection of the p.Thr790Met EGFR Alteration by Preamplification before PNA-Mediated PCR Clamping and Pyrosequencing

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 527
Author(s):  
Amandine Billaud ◽  
Veronique Verriele ◽  
Jonathan Dauvé ◽  
Louise-Marie Chevalier ◽  
Alain Morel
Keyword(s):  
First Generation ◽  
Kinase Inhibitors ◽  
Resistance Mutation ◽  
Small Cell ◽  
Therapeutic Management ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Ffpe Samples ◽  
Egfr Tyrosine Kinase Inhibitors

Targeted therapies and, more precisely, EGFR tyrosine kinase inhibitors (TKIs) have been a major improvement in the therapeutic management of EGFR-mutated non-small-cell lung cancers (NSCLCs). Earlier administration of these TKIs throughout tumor progression is imperative to improve patient outcomes. Consequently, studies have focused on refining the characterization of biomarkers, especially concerning the resistance mutation p.Thr790Met of EGFR. Herein, we developed peptide nucleic acid (PNA)-mediated PCR clamping followed by pyrosequencing, favoring enrichment of the mutated fraction. A preamplification step was first added to increase the amplifiable DNA fraction. Throughout the application of our method on DNA extracted from FFPE samples of 46 patients with NSCLC who had relapsed under first-generation EGFR TKI, we evaluated a sensitivity of 93.3% and a specificity of 100%. All 19 patients who were positive for the p.Thr790Met mutation with NGS were also found to be positive with our protocol. The only discordant case was a sample with no mutation detected with NGS, but which was positive with PNA. This protocol allows for the detection of the p.Thr790Met mutation with a sensitivity of 0.5% which will permit earlier detection and an improvement of therapeutic management.

Factors determining the distribution of introduced mammals in nature reserves of the southern province, New Caledonia

2003 ◽  
Vol 30 (2) ◽  
pp. 187 ◽  
Author(s):  
Sophie Rouys ◽  
Jörn Theuerkauf
Keyword(s):  
Rattus Norvegicus ◽  
New Caledonia ◽  
Canis Familiaris ◽  
Rattus Rattus ◽  
Nature Reserves ◽  
House Mice ◽  
Mus Musculus Domesticus ◽  
Southern Province ◽  
Feral Populations ◽  
Norway Rats

We studied the distribution of introduced mammals in six nature reserves of New Caledonia's southern province. Polynesian rats (Rattus exulans) were common in both rainforest and shrubland but their abundance decreased with increasing altitude. Ship rats (Rattus rattus) were abundant in rainforest but less numerous in shrubland and their abundance did not increase with altitude. We found no Norway rats (Rattus norvegicus) or house mice (Mus musculus domesticus) in reserves. Feral pigs (Sus scrofa) used mainly rainforest but also shrubland and preferred foraging in valleys with alluvial soils. Rusa deer (Cervus timorensis) selected shrubland over rainforest. Feral cats (Felis catus) were widely distributed in the reserves, whereas dogs (Canis familiaris) strayed into reserves but did not form feral populations.

scholarly journals Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3736
Author(s):  
Franciele H. Knebel ◽  
Louise J. Barber ◽  
Alice Newey ◽  
Dimitrios Kleftogiannis ◽  
Andrew Woolston ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Large Fraction ◽  
Single Agent ◽  
Acquired Resistance ◽  
Genetic Resistance ◽  
Resistance Mutation ◽  
Resistance Mechanisms ◽  
Wild Type ◽  
Primary Resistance ◽  
Clinical Resistance

Epidermal growth factor receptor antibodies (EGFR-Abs) confer a survival benefit in patients with RAS wild-type metastatic colorectal cancer (mCRC), but resistance invariably occurs. Previous data showed that only a minority of cancer cells harboured known genetic resistance drivers when clinical resistance to single-agent EGFR-Abs had evolved, supporting the activity of non-genetic resistance mechanisms. Here, we used error-corrected ctDNA-sequencing (ctDNA-Seq) of 40 cancer genes to identify drivers of resistance and whether a genetic resistance-gap (a lack of detectable genetic resistance mechanisms in a large fraction of the cancer cell population) also occurs in RAS wild-type mCRCs treated with a combination of EGFR-Abs and chemotherapy. We detected one MAP2K1/MEK1 mutation and one ERBB2 amplification in 2/3 patients with primary resistance and KRAS, NRAS, MAP2K1/MEK1 mutations and ERBB2 aberrations in 6/7 patients with acquired resistance. In vitro testing identified MAP2K1/MEK1 P124S as a novel driver of EGFR-Ab resistance. Mutation subclonality analyses confirmed a genetic resistance-gap in mCRCs treated with EGFR-Abs and chemotherapy, with only 13.42% of cancer cells harboring identifiable resistance drivers. Our results support the utility of ctDNA-Seq to guide treatment allocation for patients with resistance and the importance of investigating further non-canonical EGFR-Ab resistance mechanisms, such as microenvironmentally-mediated resistance. The detection of MAP2K1 mutations could inform trials of MEK-inhibitors in these tumours.

scholarly journals Patients Harboring Uncommon EGFR Exon 19 Deletion-insertion Mutations Respond Well to First-generation EGFR Inhibitors and Osimeritinib Upon Acquisition of T790M

2021 ◽  
Author(s):  
Yurong Wang ◽  
Ruipan Zheng ◽  
Peizhu Hu ◽  
Ziheng Zhang ◽  
Shujing Shen ◽  
...  
Keyword(s):  
First Generation ◽  
Resistance Mutation ◽  
Resistance Mechanisms ◽  
First Line ◽  
T790m Mutation ◽  
Similar Treatment ◽  
Significant Difference ◽  
Exon 19 Deletion ◽  
Egfr Tkis ◽  
Exon 19

Abstract Background: This study is to investigate the effects and resistance mechanisms of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients carrying rare EGFR exon 19 deletion-insertion (19delins) mutations. Methods: The next generation sequencing (NGS) data of 1783 patients diagnosed as advanced NSCLC from November 2017 to September 2020 were successively and retrospectively reviewed. 41 patients with EGFR 19delins and 41 patients with EGFR exon 19 deletion (19del) were enrolled in this study, who were given first generation EGFR TKIs as first-line therapy. Results: 17 mutation types of EGFR 19delins were identified in this study, L747_P753delinsS (10/41) and L747_A750delinsP (9/41) were the most frequent mutation types, followed by L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, median progression-free survival (mPFS) was similar in patients with EGFR 19delins to those with EGFR 19del (10.4 months vs. 13.1 months, p=0.1076). Interestingly, patients with L747_T751delinsP had a better mPFS than those with other variants (18.7 months vs. 13.1 months, p=0.035). No significant difference in mPFS was found among the three groups of gefitinib, icotinib, and erlotinb with 14.7 months, 10.9 months, and 13.1 months (p>0.05). After progression from first-line EGFR TKIs, both EGFR 19delins and EGFR 19del had similar rates of developing resistance mechanisms including EGFR T790M mutation (45.8% vs. 57.8%). Patients acquiring T790M mutation received osimeritinib as second-line treatment, and the mPFS was similar between the groups of EGFR 19delins (n=8) and EGFR 19del (n=10): 12.0 months vs. 12.2 months (p=0.97). Conclusion: Our results indicate that patients with uncommon EGFR 19delins can also benefit from first-generation EGFR TKIs treatment, having similar treatment responses and survival outcomes to those with EGFR 19del, even similar clinical outcomes from osimeritinib upon acquiring T790M resistance mutation.

scholarly journals Commensal Rodents in 19th Century Australasia: Diversity, Invasion Routes and the China Connection

2021 ◽  
Author(s):  
Andrew James Veale ◽  
Carolyn King ◽  
Wayne Johnson ◽  
Lara Shepherd
Keyword(s):  
Genetic Diversity ◽  
New Zealand ◽  
Dna Sequences ◽  
Archaeological Site ◽  
House Mice ◽  
Mus Musculus Domesticus ◽  
The South ◽  
The North ◽  
Founding Population ◽  
Norway Rats

Abstract The present genetic diversity of commensal rodent populations is often used to inform the invasion histories of these species, and as a proxy for historical events relating to the movement of people and goods. These studies assume that modern genetic diversity generally reflects early colonising events. We investigate this idea by sequencing the mitochondrial DNA of rodent bones found in a 19th-century archaeological site in The Rocks area of Sydney, Australia, the location of the first historical European port. We identified 19th-century bones from two species, Rattus norvegicus and Mus musculus domesticus. We found six genetic haplotypes in the 39 Norway rats, showing either multiple early introductions or a diverse initial founding population. One of them was identical with Norhap01 common in the North Island of New Zealand, but none was like the haplotype Norhap02 found throughout the South Island. We found three haplotypes in seven house mice, all belonging to the dominant subspecies established in Australia, M.m. domesticus. There was no evidence for M. m. castaneus or M. m. musculus having established there. We had few modern R. norvegicus and M. musculus DNA sequences from Sydney, but those we had did tentatively support the hypotheses that (1) modern samples can represent at least a preliminary estimate of historical diversities and origins, and (2) Asian haplotypes of both Norway rats and of house mice reached the South Island of New Zealand early in colonial times direct from China rather than through Port Jackson.

scholarly journals Influence of vitamin K-rich plant foods on anticoagulant baiting efficacy in wild House Mice, wild Norway Rats, and wild Black Rats

2009 ◽  
Vol 15 (2) ◽  
pp. 87 ◽  
Author(s):  
G. W. Witmer ◽  
P. W. Burke
Keyword(s):  
Vitamin K ◽  
Plant Material ◽  
Small Sample Size ◽  
Small Sample ◽  
House Mice ◽  
Plant Materials ◽  
Brussels Sprouts ◽  
Anticoagulant Rodenticides ◽  
Norway Rats ◽  
Black Rats

Rodents introduced to islands have caused the extinction of many species of animals. Anticoagulant rodenticides are relied on to eradicate rodents from these islands, but if the rodents are eating plant materials that contain high amounts of vitamin K (the antidote to anticoagulants) anticoagulant rodenticides may not be effective. In a laboratory trial, individually caged Norway Rats Rattus norvegicus, Black Rats R. rattus and House Mice Mus musculus were fed fresh plant material high in vitamin K (Collards [0.62 mg vitamin K per 100 g] and Brussels Sprouts [0.19 mg vitamin K per 100 g]) for a period of 7 days. When presented later with anticoagulant rodenticides (0.0025% brodifacoum pellets or 0.005% diphacinone pellets) along with the diet of plant material, 94% of the rodents died. We conclude from this study that the presence of green feed rich in vitamin K does not reduce the effectiveness of anticoagulant rodenticides. However, we add a word of caution on one of the findings of our study. While we think the low efficacy (75%) we found in the case of brodifacoum and Black Rats was probably an artifact of small sample size in that treatment group, the result warrants further investigation.

scholarly journals Evolution of PTH assays

2006 ◽  
Vol 50 (4) ◽  
pp. 621-627 ◽  
Author(s):  
José Gilberto H. Vieira ◽  
Ilda Kunii ◽  
Sônia Nishida
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
First Generation ◽  
Recent Observation ◽  
Cost Benefit ◽  
Molecular Forms ◽  
Specific Antibodies ◽  
Amino Terminal ◽  
2Nd Generation ◽  
Carboxyl Terminal

PTH metabolism is complex and the circulating forms include the intact 1-84 molecule as well as several carboxyl-terminal fragments. The first generation of PTH assays included several types of competitive assays, with specificities that spanned carboxyl, mid-region and amino-terminal portions of the molecule. The limitations of these assays and the methodological evolution led to the description of 2nd generation non-competitive immunometric assays for PTH in the late 80's, based on the recognition of the PTH molecule by two different antibodies, one directed against de amino-terminal and other against the carboxyl-terminal segments. The observation that in some circumstances "long" carboxyl-terminal segments were also measured by 2nd generation assays led to the development of 3rd generation assays based on amino-terminal specific antibodies that are specific for the first amino acids, measuring only the molecular forms that activate PTH1R. The practical and cost-benefit advantages of these assays are still debatable. The recent observation that carboxyl-terminal fragments of PTH have biological activity via a distinct receptor than PTH1R, points to the future need of more than one assay in order to evaluate parathyroid hormone function.

scholarly journals THE IMPACT OF NON-LOCAL ACTIVATION AND ASSOCIATED WATER PHASE PARA-STATE ON AN AQUATIC ORGANISMS DAPHNIA MAGNA LIFETIME

2019 ◽  
Vol 98 (11) ◽  
pp. 1251-1256
Author(s):  
T. I. Iksanova ◽  
D. B. Kamenetskya ◽  
A. A. Stekhin ◽  
G. V. Yakovleva ◽  
M. G. Kochetkova
Keyword(s):  
Life Expectancy ◽  
Daphnia Magna ◽  
First Generation ◽  
Second Generation ◽  
Water Phase ◽  
2Nd Generation ◽  
Water Activation ◽  
Non Local ◽  
Quantum Coupling ◽  
Local Water

Introduction. The work is devoted to the study of associated water phase magnetic state influence, represented by amorphous ice with a modified ratio of isomers in the increasing of para-water proportion, and non-local water activation based on the technology of non-local quantum water conjugation with the production activating process, on the vital hydrobionts Daphnia magna signs. Material and methods. The studies were carried out using non-locally activated drinking water “Si” and a para-water concentrate prepared in hypomagnetic conditions at a residual magnetic flux density not more than 20ntl according to the manufacturer’s technology. The para-water concentrate was introduced into the hydrobionts medium in the ratio of 9 ml per 1 liter of water under study. To obtain offspring, individuals were used, derived on the settled tap water (1st generation) and individuals, derived on the water “Si” - 2nd generation. One-day individuals of Daphnia magna were placed in the amount of 20pcs/l of the studied water and the entire life cycle were kept in optimal conditions: climatostat P-2 (temperature - 20±1°C, illumination - 1200-2500lux, photoperiod - 12/12) hour. Feeding of Daphnia was carried out by Chlorella microalgae grown on the medium “Tamiya”-50% with a density D=0.65-0.72. Results. The life expectancy of Daphnia magna hydrobionts in the non-locally activated environment (water “Si”) increases by an average of 38 days in the first generation and 50 days in the second generation, and in an environment with a potentiating additive para-water associates for 58 days (first generation) and 41 days (second generation).The life expectancy of aquatic animals is related by negative correlation with the change in values of the oxidation-reductant potential (Eh) of the environment of hydrobionts development (Corr.=-0.993 (1st generation). Both non-local water activation and spin-modification of its associated phase by para-isomers demonstrate an increase in the hydrobionts productivity: - in non-locally activated water - 1.20 (1st generation) and 2.68 (2nd generation); - in non-locally activated water with the addition of para-water - 1.39 (1st generation) and 1.97 (2nd generation) times. Conclusion. From the results it follows that the determining factor in the hydrobionts medium is its quantum coupling with electron sources in the external environment. This determines the importance of water quantum coupling with natural ecosystems, affecting cellular metabolism. Spin para modification of the associated water phase leads to an additional increase in the hydrobionts life expectancy in the first generation. In the second generation, the influence of para-water is accompanied by some decrease in both the life hydrobionts expectancy and their productivity.

A natural food aversion in Norway rats and in house mice

1981 ◽  
Vol 31 (3) ◽  
pp. 314-323 ◽  
Author(s):  
W.J. Carr ◽  
Deborah Schwartz ◽  
Edna Chism ◽  
Barbara Thomas
Keyword(s):  
House Mice ◽  
Natural Food ◽  
Food Aversion ◽  
Norway Rats

Genetic resistance of different genotypes of sheep to natural infections with gastro-intestinal nematodes

1997 ◽  
Vol 64 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Endang Romjali ◽  
V. S. Pandey ◽  
R. M. Gatenby ◽  
M. Doloksaribu ◽  
H. Sakul ◽  
...  
Keyword(s):  
First Generation ◽  
Genetic Resistance ◽  
The Body ◽  
Birth Season ◽  
Weaning Weight ◽  
Intestinal Nematode ◽  
Faecal Samples ◽  
Breeding Programmes ◽  
Nematode Eggs ◽  
Mcmaster Method

AbstractDuring a 3-year period, from April 1991 to December 1993, in a flock with four lambing periods annually, faecal samples from lambs at weaning at the age of 3 months (no. = 1756), were examined for gastro-intestinal nematode eggs by the McMaster method. Faecal samples were also examined at the age of 9 (no. = 170), 12 (no. = 157), 15 (no. = 253) and 18 (no. = 85) months from the females only. From June to December 1993 packed cell volume (PCV) was also examined from lambs at weaning. Seven genotypes were used in this study.The faecal egg counts were affected by genotype, birth season, type of birth and rearing, sex and age. First generation cross of Sumatra × Barbados Blackbelly had lowest eggs per g of faeces (EPG) followed by Sumatra, St Croix, Sumatra × St Croix Fl and F2 and Sumatra × Java Fat tail. Lambs born in February-March when rainfall was low had lower EPG (V < 0·05) than those born in May-June or August-September. The EPG of lambs born and reared singly were significantly lower (P < 0·001) than those born twin, triplet or quadruplet. Female lambs had lower EPG than male lambs (P < 0·001). The EPG of lambs at 3 months were higher than at 9, 12, 15 or 18 months (P < 0·001).PCV was affected by genotype, sex, type of birth and rearing and season of birth. There was a positive correlation between PCV and weaning weight of lambs and a negative correlation between EPG and weaning weight. These results show that the crosses of St Croix and Barbados Blackbelly with local Sumatra sheep are at least as resistant or more resistant to gastro-intestinal nematodes than pure Sumatra breed and therefore these breeds can be used in cross breeding programmes to improve the body size of local Sumatra sheep.

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