Mutations in the autoregulatory domain of β‐tubulin 4a cause hereditary dystonia

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

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Expression of ERCC1, p53, and Class III β-Tubulin Do Not Reveal Chemoresistance in Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e318218f28b ◽

2011 ◽

Vol 21 (6) ◽

pp. 1071-1077 ◽

Cited By ~ 8

Author(s):

Ingrid Vandenput ◽

An Capoen ◽

Lieve Coenegrachts ◽

Godelieve Verbist ◽

Philippe Moerman ◽

...

Keyword(s):

Endometrial Cancer ◽

Class Iii ◽

Β Tubulin

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Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

Scientific Reports ◽

10.1038/s41598-021-83513-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Malabika Chakrabarti ◽

Nishant Joshi ◽

Geeta Kumari ◽

Preeti Singh ◽

Rumaisha Shoaib ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Life Cycle ◽

Specific Protein ◽

Parasite Growth ◽

Growth And Survival ◽

Apicomplexan Parasites ◽

Parasite Replication ◽

Main Components ◽

Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

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Susceptible trichostrongyloid species mask presence of benzimidazole-resistant Haemonchus contortus in cattle

Parasites & Vectors ◽

10.1186/s13071-021-04593-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Khalid M. Mohammedsalih ◽

Jürgen Krücken ◽

Ahmed Bashar ◽

Fathel-Rahman Juma ◽

Abdalhakaim A. H. Abdalmalaik ◽

...

Keyword(s):

Haemonchus Contortus ◽

Epidemiological Data ◽

Nematode Species ◽

Parasitic Nematodes ◽

Molecular Approaches ◽

Tubulin Genes ◽

Faecal Egg Count ◽

Third Stage ◽

Before And After ◽

Β Tubulin

Abstract Background Benzimidazole (BZ) anthelmintics are widely used to control infections with parasitic nematodes, but BZ resistance is an emerging threat among several nematode species infecting humans and animals. In Sudan, BZ-resistant Haemonchus contortus populations were recently reported in goats in South Darfur State. The objective of this study was to collect data regarding the situation of BZ resistance in cattle parasitic nematodes in South Darfur using phenotypic and molecular approaches, besides providing some epidemiological data on nematodes in cattle. Methods The faecal egg count reduction test and the egg hatch test (EHT) were used to evaluate benzimidazole efficacy in cattle nematodes in five South Darfur study areas: Beleil, Kass, Nyala, Rehed Al-Birdi and Tulus. Genomic DNA was extracted from pools of third-stage larvae (L3) (n = 40) during trials, before and after treatment, and pools of adult male Haemonchus spp. (n = 18) from abattoirs. The polymorphisms F167Y, E198A and F200Y in isotype 1 β-tubulin genes of H. contortus and H. placei were analysed using Sanger and pyrosequencing. Results Prevalence of gastro-intestinal helminths in cattle was 71% (313/443). Reduced albendazole faecal egg count reduction efficacy was detected in three study areas: Nyala (93.7%), Rehed Al-Birdi (89.7%) and Tulus (88.2%). In the EHT, EC50 values of these study areas ranged between 0.032 and 0.037 µg/ml thiabendazole. Genus-specific PCRs detected the genera Haemonchus, Trichostrongylus and Cooperia in L3 samples collected after albendazole treatment. Sanger sequencing followed by pyrosequencing assays did not detect elevated frequencies of known BZ resistance-associated alleles in codon F167Y, E198A and F200Y in isotype 1 β-tubulin gene of H. placei (≤ 11.38%). However, polymorphisms were detected in H. contortus and in samples with mixed infections with H. contortus and H. placei at codon 198, including E198L (16/58), E198V (2/58) and potentially E198Stop (1/58). All pooled L3 samples post-albendazole treatment (n = 13) were identified as H. contortus with an E198L substitution at codon 198. Conclusions To the knowledge of the authors, this is the first report of reduced albendazole efficacy in cattle in Sudan and is the first study describing an E198L substitution in phenotypically BZ-resistant nematodes collected from cattle.

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A loop-mediated isothermal amplification (LAMP) assay to identify isotype 1 β-tubulin locus SNPs in synthetic double-stranded Haemonchus contortus DNA

Journal of Parasitic Diseases ◽

10.1007/s12639-021-01414-w ◽

2021 ◽

Author(s):

Livio M. Costa-Junior ◽

Umer N. Chaudhry ◽

Philip J. Skuce ◽

Seamus Stack ◽

Neil D. Sargison

Keyword(s):

Genetic Susceptibility ◽

Management Practices ◽

Anthelmintic Resistance ◽

Lamp Assay ◽

Gastrointestinal Nematode ◽

Isothermal Amplification ◽

Loop Mediated Isothermal Amplification ◽

Snp Typing ◽

Field Samples ◽

Β Tubulin

AbstractDevelopment of sustainable gastrointestinal nematode (GIN) control strategies depends on the ability to identify the frequencies of drug-susceptible and resistant genotypes in GIN populations arising from management practices undertaken on individual farms. Resistance to BZ drugs in GINs has been shown to be conferred by the presence of defined SNPs in the isotype 1 β-tubulin locus. Loop-mediated isothermal amplification (LAMP) assays are amenable to use on a range of DNA templates and are potentially adaptable to use in practical, cost-effective, pen-side diagnostic platforms that are needed to detect anthelmintic resistance in the field. In this study, we designed primers and examined LAMP assays to detect each of the three major isotype 1 β-tubulin SNPs conferring genetic susceptibility to BZ drugs. We used artificial pools of synthetic DNA, containing different proportions of susceptible and resistant SNPs to determine reproducibility of the assays. We demonstrated the detection of each of the isotype 1 β-tubulin SNPs conferring susceptibility to BZ drugs using the optimal LAMP assay. Isotype 1 β-tubulin SNP typing was effective in detecting BZ susceptibility, but the accuracy was reduced in samples with less than 60 % susceptible DNA. Our results show the potential for LAMP SNP typing to detect genetic susceptibility or resistance to anthelmintic drugs in livestock GINs, and some of the limitations in our approach that will need to be overcome in order to evaluate this assay using field samples.

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