Highly polymorphic BCR-ABL kinase domains have been reported to harbor more than a hundred mutations, and among these, 40-60% have been identified as influencers of imatinib mesylate (IM) resistance. The emergence of IM resistance poses a significant challenge in the management of Chronic Myeloid Leukemia (CML). M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance. During the study period from 2018 to 2022 (48 months), the blood samples from 219 Reverse transcriptase-PCR-confirmed CML patients following RNA extraction and cDNA preparation were subjected to M351T, E255K, and Y253H mutation analysis by PCR-RFLP. After agarose gel visualization, the samples were subjected to Sanger sequencing to confirm the nucleotide change at the polymorphic loci. The wild-type genotype of all three ABL1 SNPs under investigation exhibits a significant reduction in frequency among IM non-responders compared to the responder group. The CGT haplotype frequency exhibits a significant difference between IM responder (4.2%) and non-responder (11.8%) (p = 0.002 < 0.05). Further, CGC haplotype was observed solely among the imatinib non-responder patients with a frequency percentage of 3.3% (p = 0.004), whereas the said genotype was absent among the responder group. A reduced overall survival rate was observed with deviation from wild-type genotype (M351T loci (T > C) with 1.217 times, E255K (G > A) with 1.485 and Y253H (T > C) with 1.399 times increase in hazard ratio) thereby enhancing mortality risk due to disease progression. The significant increase in the frequency of M351T, E255K, and Y253H loci among the IM non-responder group indicated their probable association with the development of IM resistance among CML patients. A haplotype frequency distribution pattern analysis of ABL1 loci further identified the CGC haplotype as an independent predictor for IM resistance. As such the study highlights the importance of patient characteristics, genotype distribution, and haplotype frequency distribution in predicting the response to IM treatment and clinical outcomes of CML patients.

The incidence of copper-associated hepatitis in Labrador retriever in Japan has not been examined. This study examined the genotype frequencies of ATP7B:c.4358G>A, a mutation responsible for copper-associated hepatitis, and ATP7A:c.980C>T, a modifier of this disease, in Labrador retrievers of guide dog associations in Japan. Genetic material was collected by buccal swabs from 253 Labrador retrievers and genotyping was performed for the ATP7B and ATP7A mutations. The gene frequency was 0.107 for ATP7B:c.4358A. For ATP7A:c.980C, the gene frequencies were 0.703 in females and 0.368 in males. In this study, we established genotyping methods for the ATP7B:c.4358G>A and ATP7A:c.980C>T mutations. Based on the genotyping results, the risk of copper-associated hepatitis in the study population was 0.80% in males and 1.05% in females.

Milk protein comprises caseins (CNs) and whey proteins, each of which has different genetic variants. Several studies have reported the frequencies of these genetic variants and the effects of variants on milk physicochemical properties and functionality. For example, the C variant and the BC haplotype of αS1-casein (αS1-CN), β-casein (β-CN) B and A1 variants, and κ-casein (κ-CN) B variant, are favourable for rennet coagulation, as well as the B variant of β-lactoglobulin (β-lg). κ-CN is reported to be the only protein influencing acid gel formation, with the AA variant contributing to a firmer acid curd. For heat stability, κ-CN B variant improves the heat resistance of milk at natural pH, and the order of heat stability between phenotypes is BB > AB > AA. The A2 variant of β-CN is more efficient in emulsion formation, but the emulsion stability is lower than the A1 and B variants. Foaming properties of milk with β-lg variant B are better than A, but the differences between β-CN A1 and A2 variants are controversial. Genetic variants of milk proteins also influence milk yield, composition, quality and processability; thus, study of such relationships offers guidance for the selection of targeted genetic variants.

UNASSIGNED: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has been extensively studied in immune activation, roles for Arg are incompletely characterized. To investigate the role for Arg in experimental autoimmune encephalomyelitis, we studied disease development in Arg-/- mice.
UNASSIGNED: Arg-/- and Arg+/+ mice were generated from breeding of Arg+/- mice on the C57BL/6 background. Mice were immunized with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide and disease development recorded. Lymphocyte phenotypes of wild type Arg+/+ and Arg-/- mice were studied by in vitro stimulation assays and flow cytometry.
UNASSIGNED: The breeding of Arg+/+ and Arg-/- mice showed skewing in the frequency of born Arg-/- mice. Loss of Arg function did not affect development of experimental autoimmune encephalomyelitis, but reduced the number of splenic B-cells in Arg-/- mice following immunization with MOG peptide.
UNASSIGNED: Development of MOG-induced experimental autoimmune encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development.

(1) Background: Assignment of pathogens to the correct genus, species, and type is vital for controlling infectious epidemics. However, the role of different enteroviruses during hand, foot, and mouth disease (HFMD) epidemics and the major contributing factors remain unknown. (2) Methods: HFMD cases from 2016 to 2018 in Guangzhou, China were collected. The relationship between HFMD cases and genotype frequency, as well as the association between genotype frequency and climate factors, were studied using general linear models. We transformed the genotype frequency to the isometric log-ratio (ILR) components included in the model. Additionally, vaccination rates were adjusted in the climate-driven models. (3) Results: We observed seasonal trends in HFMD cases, genotype frequency, and climate factors. The model regressing case numbers on genotype frequency revealed negative associations with both the ILRs of CAV16 (RR = 0.725, p < 0.001) and EV71 (RR = 0.421, p < 0.001). The model regressing genotype frequency on driven factors showed that the trends for EV71 proportions were inversely related to vaccination rate (%, β = -0.152, p = 0.098) and temperature (°C, β = -0.065, p = 0.004). Additionally, the trends for CVA16 proportions were inversely related to vaccination rate (%, β = -0.461, p = 0.004) and temperature (°C, β = -0.068, p = 0.031). The overall trends for genotype frequency showed that EV71 decreased significantly, while the trends for CVA16 increased annually. (4) Conclusions: Our findings suggest a potential pathway for climate factors, genotype frequency, and HFMD cases. Our study is practical and useful for targeted prevention and control, and provides environmental-based evidence.

OBJECTIVE: : Insecticide applied at optimum dosage and coverage delays the development of resistance in disease vectors. The study was aimed to test the hypothesis whether decrease in exposure to insecticide leads to decrease in selection of insecticide resistance in mosquitoes. The mosquitoes were variably exposed to insecticide in the laboratory by simulating the variations in insecticide sprays applied in the field.
METHODS: : The study was carried out on DDT resistant adults of Anopheles stephensi. Mosquitoes were differentially exposed to impregnated papers of DDT (4%), that were differentially masked to 25, 50, and 75% area with an unimpregnated Whatman No.1 filter paper, and to a positive control without any masking, i.e. 100% exposure area. The study was conducted for five generations and at each generation mosquitoes were exposed to differentially masked impregnated papers, and percent mortality was calculated.
RESULTS: : The observed survival rate in differential exposures was more with the increase in heterozygous genotype resistance-susuceptible (RS) frequency. Resistant gene frequency with differential exposures (25 to 75%) was in the range of 0.38-0.54 for the F0 generation, which increased to 0.84-0.93 for the F4 generation. In 100% exposure it was 0.18 in F0 generation, which increased to 0.58 in the F4 generation. The resistant gene frequencies in the population showed increasing trend with decrease in exposure in contrast to complete exposure.
CONCLUSIONS: : Variable simulated exposures resulted in precipitation of increased resistance while complete exposure resulted in lower levels of resistance, signifying the importance of optimum dosage and coverage in the indoor residual spray in delaying/avoiding the development of insecticide resistance in the disease vectors.

Although only a few specific pigmentation types are allowed within the Hucul horse registry, accurate determination of particular coat colors can be uncertain due to the presence of variation in color shades and segregation of multiple dun dilution variants. Herein, we genotyped the previously identified polymorphisms within two coat color loci TBX3 (T-box 3) and ASIP (Agouti Signaling Protein) in 462 Hucul individuals and compared the genotype predicted phenotypes with observed pigmentation types provided in the Polish Horse Breeders Association database. We identified disagreement between the predicted and recorded coat color in 157 horses (34%). The most common error was misclassification of horses with the nd1/nd1 and nd1/nd2 genotypes, what may be related with the occurrence of some \'intermediate\' dilution phenotypes in such individuals. We have also proven that the frequency of the dominant dun dilution allele (D) (0.30) is higher than previously predicted by available studbooks. The D allele(s) is easily \'hidden\' in various phenotypic groups including dark bay and black, therefore we hypothesized that the dun dilution effect itself is not as strongly epistatic in the Hucul horse as described in other horse breeds. This may be the result of an additional genetic modifier suppressing D allele phenotypic effect.

Biological control agents usually suffer from a shortage of target prey or hosts in their post-release stage. Some predatory agents turn to attacking other prey organisms, which may induce physiological and evolutionary changes. In this study, we investigated life history traits, gene expression and genotype frequency in the predatory ladybird beetle Cryptolaemus montrouzieri during experimental prey shifts. C. montrouzieri were either continuously fed on aphids Megoura japonica as an alternative prey for four generations or were shifted back to the initial prey mealybugs Planococcus citri in each generation. In general, the utilization of aphids resulted in reduced performance and severe physiological adjustments, indicated by significant changes in development and fecundity traits and a large number of differentially expressed genes between the two offering setup prey treatments. Within the aphid-fed lines, performance regarding the developmental time, the adult weight and the survival rate recovered to some level in subsequent generations, possibly as a result of adaptive evolution. In particular, we found that a shift back to mealybugs caused a gradual increase in fecundity. Accordingly, a genotype of the fecundity-related gene vitellogenin, of which there were several minor alleles in the initial population, became the main genotype within four generations. The present study explored the short-term experimental evolution of a so-call specialist predator under prey shift conditions. This potential rapid adaptation of biological control agents to novel prey will increase environmental risks associated with non-target effects.

BACKGROUND: There is an accumulating body of evidence indicating a strong association between inflammation and the pathogenesis of atrial fibrillation (AF) in different ethnicities across the globe. AF increases the risk of stroke and heart failure. Despite various researches on IL-10 response, there is limited clinical evidence present, which demonstrate a role of these immunity regulators in AF. Therefore, this study was designed to decipher the role of IL-10(-592A/C) polymorphism in the development of postoperative AF (post-OP AF).
METHODS: The study was designed for north Indian patients. The study included 90 patients with AF and 126 controls in sinus rhythm undergoing surgery at Department of Cardiovascular and thoracic surgery, SGPGIMS, Lucknow, India. DNA samples were genotyped for common single nucleotide polymorphism (SNP) in gene IL-10(-592A/C). The PCR-based RFLP technique was used to assess the genotype frequencies. The multivariable logistic regression analysis was performed to study the association of other risk factors with AF.
RESULTS: The distribution of IL-10(-592A/C) genotypes (CC, AC, and AA) was found to be 48.41%, 47.61%, and 3.98% in controls and 41.11%, 45.55%, and 13.34% in cases, respectively (P = .0385). The frequency of allele A in cases was significantly higher than the control group (36.11% vs 27.77%, P = .0654). Compared with CC, AA genotype had increased risk of AF in both unadjusted and adjusted analyses.
CONCLUSIONS: This study suggests that IL-10(-592A/C) polymorphism may have significant association with post-OP AF development in north Indian patients.

Individuals with the human neutrophil antigen (HNA)-3b/3b type can produce HNA-3a antibodies, which have been reported to cause severe, sometimes fatal transfusion-related acute lung injury (TRALI). Our study aimed to determine the genotype frequency of HNA-3a/3b which will be helpful to estimate the potential risk for forming anti-HNA-3a, the clinically relevant antibody linked to TRALI in two different ethnic groups of southern China. Five hundred unrelated and healthy blood donors (284 male, 216 female; 300 Zhuangs, 200 Dongs) from the Guangxi Zhuang Autonomous Region were simultaneously typed for the HNA-3 allele using a polymerase chain reaction sequence-based typing (PCR-SBT) method. Genotype frequencies of HNA-3a/3a, HNA-3a/3b and HNA-3b/3b were 51.7%, 39.7% and 8.6% in the Zhuang population, and 44.0%, 49.0% and 7.0% in the Dong population, respectively. Homozygous HNA-3b/3b genotype frequency among the Zhuang population (8.6%) was significantly higher than previously reported in African Americans (0.4%), Brazilians (3.6%) and English Caucasians (2.9%) (p < .05). And the HNA-3b/3b genotype frequency among the Dong population was higher than African Americans (0.4%) (p < .05). This study showed Chinese Zhuang and Dong populations possessed a higher frequency of HNA-3b/3b genotype, suggesting that they may be at greater risk for developing anti-HNA-3a alloantibodies that may cause severe cases of TRALI. A molecular-based identification of the HNA-3b/3b genotype in all multiparous female blood donors was suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusions.