Experimental and molecular genetic analysis of the impact of pyrethroid and non-pyrethroid insecticide impregnated bednets for mosquito control in an area of pyrethroid resistance

2000 ◽  
Vol 90 (2) ◽  
pp. 125-132 ◽  
Author(s):  
J.H. Kolaczinski ◽  
C. Fanello ◽  
J.-P. Hervé ◽  
D.J. Conway ◽  
P. Carnevale ◽  
...  
Keyword(s):  
Mosquito Control ◽  
Pyrethroid Resistance ◽  
Molecular Genetic ◽  
Residual Activity ◽  
Molecular Genetic Analysis ◽  
Promising Alternative ◽  
Pirimiphos Methyl ◽  
Selection For ◽  
Mammalian Toxicity ◽  
The Impact

AbstractExperimental huts in Côte d’Ivoire were used to evaluate the pyrethroid alpha-cypermethrin, the non-ester pyrethroid etofenprox, the organophosphate pirimiphos-methyl and the carbamate carbosulfan on bednets against pyrethroid-resistant Anopheles gambiae Giles. To test for selection for the resistance gene by the treated nets, A. gambiae collected live or dead from the huts were kept and analysed for the presence of the kdr gene using a new polymerase chain reaction followed by sequence-specific oligonucleotide probing (PCR–SSOP) for kdr-genotyping. Deliberately holed bednets freshly treated with pirimiphos-methyl or carbosulfan caused over 90% kill of A. gambiae s.s. and Culex spp. However, the mortality with alpha-cypermethrin or etofenprox treated nets was similar to that with untreated nets. Bloodfeeding of A. gambiae s.s. on the sleepers under the nets was only significantly reduced by alpha-cypermethrin and carbosulfan. Tests of the residual activity of the bednets after seven months showed that pirimiphos-methyl had lost its efficacy while carbosulfan still performed well. Once again the pyrethroid treated nets gave similar results to the untreated nets. Selection for the kdr-allele by alpha-cypermethrin and etofenprox, but not by carbosulfan, was indicated by PCR–SSOP genotyping of mosquitoes. Thus carbamates such as carbosulfan, or organophosphates of longer persistence than pirimiphos-methyl and of low mammalian toxicity, would seem to be a promising alternative to be used on bednets, particularly in areas of pyrethroid resistance.

scholarly journals Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis

2020 ◽  
Author(s):  
Ruijie Sun ◽  
Shu-Yan Liu ◽  
Xiao-Mei Zhang ◽  
Jing-Jing Zhu ◽  
Dai Yuan ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Signaling Pathway ◽  
Molecular Genetic ◽  
Genomic Analysis ◽  
Akt Signaling ◽  
Molecular Genetic Analysis ◽  
Missense Mutations ◽  
Functional Connections ◽  
Molecular Features ◽  
The Impact

Abstract Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. In this research, we conducted an in-depth genomic analysis of a cohort of patients and elucidate molecular features associated with disease pathogenesis of ITP. High-molecular-weight genomic DNA was extracted from freshly frozen BMBMCs (bone marrow blood mononuclear cell) in 20 active ITP patients. After this, the samples were subjected to molecular genetic analysis by whole-exome sequencing technique (WES) then, confirmed by sanger sequencing method. The enriched signaling pathway analysis and cellular processes associated with the mutated genes was performed with gene mapping to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results of this study showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including PTEN, INSR and COCH were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B (PI3K/Akt) signaling pathways (signal transduction) and platelet activation (immune system). Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.

Correlation of baseline molecular and clinical variables with ALK inhibitor efficacy in ALTA-1L.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9517-9517 ◽  
Author(s):  
D. Ross Camidge ◽  
Huifeng Niu ◽  
Hye Ryun Kim ◽  
James Chih-Hsin Yang ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Molecular Genetic ◽  
Unmet Need ◽  
Molecular Genetic Analysis ◽  
Plasma Samples ◽  
Mutation Status ◽  
Clinical Variables ◽  
First Line Therapy ◽  
Intent To Treat ◽  
The Impact

9517 Background: Efficacy of ALK TKIs in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) varies. We evaluated the impact of EML4-ALK fusion variants and other baseline (BL) molecular and clinical variables on clinical efficacy of brigatinib (BRG) vs crizotinib (CRZ) as first ALK TKI therapy in pts with ALK+ NSCLC in the phase 3 ALTA-1L (NCT02737501) trial. Methods: Plasma samples were collected at screening for molecular genetic analysis of ALK and other genes implicated in NSCLC by next-generation sequencing. Exploratory analyses were performed to identify associations of clinical outcomes with oncogenic alterations including ALK fusion variants and TP53 status. Results: 124 BL samples were collected from 136 BRG-treated pts and 127 from 137 CRZ-treated pts. Pts with plasma samples were representative of the intent-to-treat population. BL ALK fusion detection rate was 52% (65/124) and 54% (68/127) in the BRG and CRZ arms, respectively, of which 83% (54/65) and 93% (63/68) were EML4-ALK fusions. In pts with detectable EML4-ALK fusions, the three predominant EML4-ALK fusion variants (V1, V2, V3) were equally distributed between arms; V1 and V3 were most prevalent (BRG/CRZ: V1, 42%/47%; V3, 42%/33%) but V1 was more frequent than V3 in pts without BL brain metastasis (47% vs 36%) or prior chemotherapy (45% vs 35%). Gender and age did not impact variant type. BRG showed higher ORR and improved mPFS vs CRZ in all variant subgroups; pts with V3 had poorer PFS compared with V1 and V2 regardless of treatment (Table). In pts with V3, BRG showed significantly improved PFS (HR=0.273, 95% CI 0.125, 0.597) and higher ORR (84% vs 67%) vs CRZ. TP53 mutation was detected in 30% (37/124) of pts in BRG arm and 26% (33/127) in CRZ arm. In pts with detectable ALK fusion, TP53 mutation showed poorer PFS in both arms than nonmutant/undetected cases (Table). BRG had better ORR and PFS vs CRZ in pts regardless of TP53 mutation status. Additional analyses of BL variables are ongoing. Conclusions: EML4-ALK fusion variant 3 and TP53 mutation were identified as poor prognosis biomarkers in ALK+ NSCLC. BRG demonstrated better efficacy than CRZ as first-line therapy in pts regardless of EML4-ALK fusion variant and TP53 mutation status. These findings may help define areas of greatest unmet need. Clinical trial information: NCT02737501 . [Table: see text]

ANALYSIS OF XENOBIOTIC DETOXIFICATION AND DNA-REPAIR GENES IN POPULATIONS LIVING IN PESTICIDE CONTAMINATED AREAS

Vestnik ◽  
2021 ◽  
pp. 202-210
Author(s):  
А. Анарбекова ◽  
Ж. Турсунова ◽  
Р. Мусабаев ◽  
И. Киселев ◽  
А. Гаршин ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chromosomal Aberrations ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Repair Gene ◽  
Xenobiotic Detoxification ◽  
Pesticide Pollution ◽  
Dna Repair Gene ◽  
Xrcc3 Thr241met ◽  
The Impact

Проведена оценка риска влияния многолетней пестицидной загрязненности окружающей среды на генетический статус населения, проживающего в 5 населенных пунктах Талгарского района (пп. Кызылкайрат, Бескайнар, Бельбулак, Амангельды, Енбекши) Алматинской области, где располагаются неутилизированные, запрещенные к использованию пестициды класса СОЗ. Результаты цитогенетического анализа населения, подверженного действию пестицидов, выявили высокую частоту хромосомных аберраций, превышающую контрольные показатели от 2,2 до 3,6 раз. Молекулярно-генетический анализ выявил повышенную частоту нефункциональных аллелей глутатион-S-трансфераз M1 и Т1 типов, что может оказывать влияние на снижение функций детоксикации ксенобиотиков у обследованного населения. Определена достоверная ассоциативная связь полиморфизма гена репарации ДНК XRCC3 Thr241Met, с повышенной частотой хромосомных аберраций у населения, проживающего вблизи очагов пестицидного загрязнения. The risk assessment of the impact of long-term pesticide pollution of the environment on the genetic status of the population living in 5 settlements of the Talgar district (Kyzylkairat, Beskaynar, Belbulak, Amangeldy, Enbekshi) of Almaty region, where unused, banned for use POPs pesticides are located, has been carried out. The results of cytogenetic analysis of the population exposed to pesticides revealed a high frequency of chromosomal aberrations, exceeding the control values from 2.2 to 3.6 times. Molecular genetic analysis revealed an increased frequency of non-functional alleles of glutathione-S-transferases of M1 and T1 types, which may affect a decrease in the functions of detoxification of xenobiotics in the surveyed population. A reliable associative relationship of the XRCC3 Thr241Met DNA repair gene polymorphism with an increased frequency of chromosomal aberrations in the population living near foci of pesticide contamination was determined.

scholarly journals Can anything be done to maintain the effectiveness of pyrethroid–impregnated bednets against malaria vectors?

1998 ◽  
Vol 353 (1376) ◽  
pp. 1769-1775 ◽  
Author(s):  
C. F. Curtis ◽  
J. E. Miller ◽  
M. H. Hodjati ◽  
J. H. Kolaczinski ◽  
I. Kasumba
Keyword(s):  
West Africa ◽  
Growth Regulator ◽  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Insect Growth Regulator ◽  
Malaria Vectors ◽  
Cross Resistance ◽  
Laboratory Studies ◽  
Selection For ◽  
The Impact

Pyrethroid–treated bednets are the most promising available method of controlling malaria in the tropical world. Every effort should be made to find methods of responding to, or preventing, the emergence of pyrethroid resistance in the Anopheles vectors. Some cases of such resistance are known, notably in An. gambiae in West Africa where the kdr type of resistance has been selected, probably because of the use of pyrethroids on cotton. Because pyrethroids are irritant to mosquitoes, laboratory studies on the impact of, and selection for, resistance need to be conducted with free–flying mosquitoes in conditions that are as realistic as possible. Such studies are beginning to suggest that, although there is cross–resistance to all pyrethroids, some treatments are less likely to select for resistance than others are. Organophosphate, carbamate and phenyl pyrazole insecticides have been tested as alternative treatments for nets or curtains. Attempts have been made to mix an insect growth regulator and a pyrethroid on netting to sterilize pyrethroid–resistant mosquitoes that are not killed after contact with the netting. There seems to be no easy solution to the problem of pyrethroid resistance management, but further research is urgently needed.

scholarly journals Molecular Genetic Analysis of the Virulence of Oral Bacterial Pathogens: An Historical Perspective

2003 ◽  
Vol 14 (5) ◽  
pp. 331-344 ◽  
Author(s):  
Howard K. Kuramitsu
Keyword(s):  
Genetic Analysis ◽  
Historical Perspective ◽  
Recombinant Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Nucleotide Sequencing ◽  
Whole Genome ◽  
Oral Diseases ◽  
Oral Pathogens ◽  
The Impact

This review will focus on the impact of molecular genetic approaches on elucidating the bacterial etiology of oral diseases from an historical perspective. Relevant results from the pre- and post-recombinant DNA periods will be highlighted, including the roles of gene cloning, mutagenesis, and nucleotide sequencing in this area of research. Finally, the impact of whole-genome sequencing on deciphering the virulence mechanisms of oral pathogens, along with new approaches to control these organisms, will be discussed.

scholarly journals Which indoor residual spraying insecticide best complements standard pyrethroid long-lasting insecticidal nets for improved control of pyrethroid resistant malaria vectors?

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245804
Author(s):  
Thomas Syme ◽  
Augustin Fongnikin ◽  
Damien Todjinou ◽  
Renaud Govoetchan ◽  
Martial Gbegbo ◽  
...  
Keyword(s):  
Vector Control ◽  
Mosquito Control ◽  
Indoor Residual Spraying ◽  
Residual Effect ◽  
Blood Feeding ◽  
Additive Effect ◽  
Malaria Vectors ◽  
Vector Population ◽  
Pirimiphos Methyl ◽  
The Impact

Background Where resources are available, non-pyrethroid IRS can be deployed to complement standard pyrethroid LLINs with the aim of achieving improved vector control and managing insecticide resistance. The impact of the combination may however depend on the type of IRS insecticide deployed. Studies comparing combinations of pyrethroid LLINs with different types of non-pyrethroid IRS products will be necessary for decision making. Methods The efficacy of combining a standard pyrethroid LLIN (DuraNet®) with IRS insecticides from three chemical classes (bendiocarb, chlorfenapyr and pirimiphos-methyl CS) was evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae s.l. in Cové, Benin. The combinations were also compared to each intervention alone. WHO cylinder and CDC bottle bioassays were performed to assess susceptibility of the local An. gambiae s.l. vector population at the Cové hut site to insecticides used in the combinations. Results Susceptibility bioassays revealed that the vector population at Cové, was resistant to pyrethroids (<20% mortality) but susceptible to carbamates, chlorfenapyr and organophosphates (≥98% mortality). Mortality of wild free-flying pyrethroid resistant An. gambiae s.l. entering the hut with the untreated net control (4%) did not differ significantly from DuraNet® alone (8%, p = 0.169). Pirimiphos-methyl CS IRS induced the highest mortality both on its own (85%) and in combination with DuraNet® (81%). Mortality with the DuraNet® + chlorfenapyr IRS combination was significantly higher than each intervention alone (46% vs. 33% and 8%, p<0.05) demonstrating an additive effect. The DuraNet® + bendiocarb IRS combination induced significantly lower mortality compared to the other combinations (32%, p<0.05). Blood-feeding inhibition was very low with the IRS treatments alone (3–5%) but increased significantly when they were combined with DuraNet® (61% - 71%, p<0.05). Blood-feeding rates in the combinations were similar to the net alone. Adding bendiocarb IRS to DuraNet® induced significantly lower levels of mosquito feeding compared to adding chlorfenapyr IRS (28% vs. 37%, p = 0.015). Conclusions Adding non-pyrethroid IRS to standard pyrethroid-only LLINs against a pyrethroid-resistant vector population which is susceptible to the IRS insecticide, can provide higher levels of vector mosquito control compared to the pyrethroid net alone or IRS alone. Adding pirimiphos-methyl CS IRS may provide substantial improvements in vector control while adding chlorfenapyr IRS can demonstrate an additive effect relative to both interventions alone. Adding bendiocarb IRS may show limited enhancements in vector control owing to its short residual effect.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

2013 ◽  
Vol 20 (1-2) ◽  
pp. 1-8
Author(s):  
MM Rahman ◽  
L Rahman ◽  
SN Begum ◽  
F Nur
Keyword(s):  
Genetic Distance ◽  
Gene Diversity ◽  
Random Amplified Polymorphic Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polymorphic Loci ◽  
Rice Genotypes ◽  
High Level ◽  
Genetic Diversity Study ◽  
Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Nei’s genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 – 8, 2009

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

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