Abstract Methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine and folic acid metabolism. Tumour suppressor protein TP53 gene maintains cellular and genetic integrity. To date, no studies associated the MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 with CRP levels and methotrexate (a folic acid antagonist) treatment outcomes in psoriatic arthritis (PsA) patients. The present study aimed to investigate whether the MTHFR rs1801133 and TP53 rs1042522 gene variants influences CRP levels and methotrexate treatment outcomes in South African Indian and Caucasian PsA patients. PsA patients (n=114) and healthy controls (n=100) were genotyped for the rs1801133 and rs1042522 using RFLP-PCR. (i) Results for rs1801133 genotyping: Caucasian patients had a higher frequency of the variant T-allele versus healthy Caucasian controls (40% versus 22%; OR=2.31, 95% CI=1.10-4.88, p=0.0379). Patients with the variant CT+TT genotypes had higher median CRP levels at baseline versus wildtype CC genotypes (11.70 (5.3-28.80) mg/mL versus 7.40 (5.00-15.05) mg/mL, p=0.0355). After 6 months of methotrexate treatment median CRP levels between genotypes reduced and remained similar. (ii) Results for rs1042522 genotyping: Indian patients had a higher frequency of the variant Arg-allele versus healthy Indian controls (42% versus 29%; OR=1.75, 95% CI=1.07-2.86, p=0.0275). In conclusion, patients with the MTHFR rs1801133 variant T-allele have elevated CRP levels, which can be ameliorated with methotrexate. (MTHFR metabolism TP TP5 integrity date CT C T rs rs180113 ProArg Pro Arg rs104252 antagonist (PsA n=114 n114 n 114 (n=114 n=100 n100 100 (n=100 RFLPPCR. RFLPPCR RFLP PCR. PCR RFLP-PCR i (i genotyping Tallele allele 40% 40 (40 22% 22 OR231 OR 2 31 OR=2.31 95 CI=1.104.88, CI110488 CI CI=1.10 4.88, 1 10 4 88 CI=1.10-4.88 p=0.0379. p00379 p p=0.0379 . 0 0379 p=0.0379) CTTT TT 11.70 1170 11 70 (11.7 5.328.80 532880 5.3 28.80 5 3 28 80 (5.3-28.80 mgmL mg mL 740 7 7.4 5.0015.05 5001505 5.00 15.05 00 15 05 (5.00-15.05 p=0.0355. p00355 p=0.0355 0355 p=0.0355) similar ii (ii Argallele 42% 42 (42 29% 29 OR175 75 OR=1.75 CI=1.072.86, CI107286 CI=1.07 2.86, 07 86 CI=1.07-2.86 p=0.0275. p00275 p=0.0275 0275 p=0.0275) conclusion rs18011 rs10425 n=11 n11 (n=11 n=10 n10 (n=10 (4 OR23 OR=2.3 9 104 CI=1.104.88 CI11048 CI110 CI=1.1 488 4.88 8 CI=1.10-4.8 p0037 p=0.037 037 11.7 117 (11. 328 5.328.8 53288 53 5. 2880 28.8 (5.3-28.8 74 7. 0015 5.0015.0 500150 500 5.0 1505 15.0 (5.00-15.0 p0035 p=0.035 035 OR17 OR=1.7 072 CI=1.072.86 CI10728 CI107 CI=1.0 286 2.86 CI=1.07-2.8 p0027 p=0.027 027 rs1801 rs1042 n=1 n1 (n=1 ( OR2 OR=2. CI=1.104.8 CI1104 CI11 CI=1. 48 4.8 CI=1.10-4. p003 p=0.03 03 11. (11 32 5.328. 5328 288 28. (5.3-28. 001 5.0015. 50015 50 150 15. (5.00-15. OR1 OR=1. CI=1.072.8 CI1072 CI10 2.8 CI=1.07-2. p002 p=0.02 02 rs180 rs104 n= (n= OR=2 CI=1.104. CI1 CI=1 4. CI=1.10-4 p00 p=0.0 (1 5.328 532 (5.3-28 5.0015 5001 (5.00-15 OR=1 CI=1.072. 2. CI=1.07-2 rs18 rs10 (n OR= CI=1.104 CI= CI=1.10- p0 p=0. 5.32 (5.3-2 5.001 (5.00-1 CI=1.072 CI=1.07- rs1 p=0 (5.3- (5.00- p= (5.3 (5.00 (5. (5.0 (5

Abstract The progressive fragmentation and loss of habitats represent the main threats for endangered species, causing genetic consequences that may have potential implications for a population’s long-term persistence. Large mammals are the most affected species among vertebrates. The giant armadillo Priodontes maximus is a large South American mammal threatened species, showing nocturnal, solitary and fossorial behavior, occurring at low population densities, and its population dynamics are still poorly known. In this study, we carried out the first assessment of genetic variability and population genetic structure of the species, using a panel of 15 polymorphic microsatellites developed by high-throughput genome sequencing. The spatial Bayesian clustering, Fst and Dest results indicated the presence of two genetic clusters (K = 2) in the study area. These results suggest a reduction in gene flow between individuals inhabiting the Brazilian savanna (Cerrado) and the Pantanal wetlands, with the increased human-driven habitat modifications possibly contributing for this scenario. A bottleneck signal was detected in both populations, and a subpopulation structuring in the Cerrado may also be reflecting consequences of the extensive habitat modifications. Findings from this study provide important and useful information for the future maintenance of genetic diversity and long-term conservation of this flagship species. populations s longterm long term persistence vertebrates nocturnal behavior densities known 1 highthroughput high throughput sequencing clustering K 2 area (Cerrado wetlands humandriven human driven scenario

Abstract Drosophila melanogaster is undoubtedly one of the most useful model organisms in biology. Initially used in solidifying the principles of heredity, and establishing the basic concepts of population genetics and of the synthetic theory of evolution, it can currently offer scientists much more: the possibility of investigating a plethora of cellular and biological mechanisms, from development and function of the immune system to animal neurogenesis, tumorigenesis and beyond. Extensive resources are available for the community of Drosophila researchers worldwide, including an ever-growing number of mutant, transgenic and genomically-edited lines currently carried by stock centers in North America, Europe and Asia. Here, we provide evidence for the importance of stock centers in sustaining the substantial increase in the output of Drosophila research worldwide in recent decades. We also discuss the challenges that Brazilian Drosophila scientists face to keep their research projects internationally competitive, and argue that difficulties in importing fly lines from international stock centers have significantly stalled the progression of all Drosophila research areas in the country. Establishing a local stock center might be the first step towards building a strong local Drosophila community that will likely contribute to all areas of life sciences research. biology heredity evolution more mechanisms neurogenesis beyond evergrowing ever growing mutant genomicallyedited genomically edited America Asia Here decades competitive country

Abstract Bougainvillea is a popular ornamental plant. Although Bougainvillea is abundant in germplasm resources, cultivars and flower colors, there is no rare blue colour varieties, due to the absence of delphinidin-based anthocyanins. This study analyzed the Bougainvillea leaf and bract transcriptome to select hosts of genetic transformation that would be suitable for the accumulation of delphinidin. A total of 36 gigabyte (GB) of raw data was obtained by transcriptome sequencing, with 4,058 significantly differentially expressed genes, including 1,854 upregulated and 2,204 downregulated genes. Annotation of these genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Through annotation, two CHS genes, one F3H gene, one DFR gene, and one F3'H gene involved in the delphinidin biosynthesis pathway were identified. The expression levels of these genes and total flavonoid content in the bracts of six Bougainvillea varieties were examined through quantitative real-time PCR and spectrophotometry, respectively. Through the comprehensive evaluation based on membership function method, the suitable host order for a blue-hued Bougainvillea transgene is Singapore White>Elizabeth Angus>Ratana Yellow>China Beauty>Orange King>Brilliant Variegata. Thus, Singapore White variety was the most appropriate transgene host for blue-hued Bougainvillea. The results of this study provide a reference for the directed breeding of blue-hued Bougainvillea. plant resources colors delphinidinbased anthocyanins 3 GB (GB sequencing 4058 4 058 4,05 1854 1 854 1,85 2204 2 204 2,20 databases annotation FH F H F3 identified realtime real time spectrophotometry respectively method bluehued hued WhiteElizabeth Elizabeth AngusRatana Angus Ratana YellowChina Yellow China BeautyOrange Beauty Orange KingBrilliant King Brilliant Variegata Thus 405 05 4,0 185 85 1,8 220 20 2,2 40 0 4, 18 8 1, 22 2,

Abstract ABT737 is used as a specific BCL2 inhibitor, which can treat papillary thyroid carcinoma (PTC). However, the effect of ABT737 on PTC cell apoptosis is limited. Moreover, BCL2 inhibition causes the activation of Beclin1-dependent autophagy. Our study aimed to explore the effects of autophagy and Beclin1 on ABT737 efficacy in PTC. The experimental data showed that ABT737 synchronously enhanced autophagic activity and apoptosis level in PTC cells. ABT737 also promoted the dissociation of BCL2-Beclin1 and BCL2-Bax complexes. Autophagy inhibitors, Bafilomycin A1 and 3-MA, enhanced the inhibitory effect of ABT737 on the survival and function in PTC cells. Consistently, autophagy inhibition with Beclin1 pharmacological inhibitor (spautin-1) also enhanced the efficacy of ABT737. Additionally, ABT737 at low-dose promoted LC3 conversion in PTC cells, and did not affect PTC cell apoptosis and survival. However, The efficacy of low-dose of ABT737 in PTC cell apoptosis and survival was displayed with the addition of Bafilomycin A1, 3-MA or spautin-1. In conclusion, the limited role of ABT737 in PTC cell apoptosis is attributed to its promoting effect on Beclin1-dependent autophagy. Therefore, autophagy inhibition based on Beclin1 downregulation can enhance the sensitivity of PTC cells to ABT737-induced death. ABT ABT73 BCL . (PTC) However Moreover Beclin1dependent Beclindependent dependent Beclin BCL2Beclin1 BCLBeclin BCL2-Beclin BCL2Bax BCLBax Bax complexes inhibitors A 3MA, 3MA MA 3 MA, Consistently spautin1 spautin 1 (spautin-1 Additionally lowdose low dose LC spautin1. 1. spautin-1 conclusion Therefore ABT737induced ABTinduced induced death ABT7 (PTC BCL2Beclin (spautin- spautin- (spautin

Abstract Leguminous plants can establish endosymbiotic relationships with nitrogen-fixing soil rhizobacteria. Bacterial infection and nodule organogenesis are two independent but highly coordinated genetic programs that are active during this interaction. These genetic programs can be regulated along all the stages of gene expression. Most of the studies, for both eukaryotes and prokaryotes, focused on the transcriptional regulation level determining the abundance of mRNAs. However, it has been demonstrated that mRNA levels only sometimes correlate with the abundance or activity of the coded proteins. For this reason, in the past two decades, interest in the role of translational control of gene expression has increased, since the subset of mRNA being actively translated outperforms the information gained only by the transcriptome. In the case of legume-rhizobia interactions, the study of the translatome still needs to be explored further. Therefore, this review aims to discuss the methodologies for analyzing polysome-associated mRNAs at the genome-scale and their contribution to studying translational control to understand the complexity of this symbiotic interaction. Moreover, the Dual RNA-seq approach is discussed for its relevance in the context of a symbiotic nodule, where intricate multi-species gene expression networks occur. nitrogenfixing nitrogen fixing rhizobacteria interaction studies prokaryotes However proteins reason decades increased transcriptome legumerhizobia legume rhizobia interactions further Therefore polysomeassociated polysome associated genomescale genome scale Moreover RNAseq RNA seq multispecies multi species occur

Abstract Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor β (TGFβ) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research. GDF (GDF11 MSTN/GDF8 MSTNGDF8 MSTNGDF GDF8 (MSTN/GDF8 TGFβ (TGFβ superfamily homology tissue sequencing replicates CC C C2C1 cultures highthroughput high throughput GDF1 respectively addition established concentrationdependent concentration dependent 3 Notably GADD45 GADD SMAD7 SMAD EGR1, EGR1 EGR 1, EGR-1 HOXA overrepresentation over representation analysis pathways GOterms GO terms processes biosynthesis phosphorylation (GDF1 MSTN/GDF (MSTN/GDF C2C GADD4 EGR- (GDF

Abstract Major histocompatibility complex (MHC) allelic polymorphism is critically important for mediating antigen presentation in vertebrates. Presently, there are insufficient studies of MHC genetic diversity in domestic Anseriform birds. In this study, we analyzed the expression profile of MHC I genes and screened for MHC I exon 2 polymorphism in one domestic goose population from China using Illumina MiSeq sequencing. The results showed that four MHC I alleles (Ancy-IE2*09/*11/*13/*21) in one goose were identified based on cDNA cloning and sequencing using four primer combinations, and the varying number of cDNA clones implied that these four classical sequences showed differential expression patterns. Through next-generation sequencing, 27 alleles were obtained from 68 geese with 3-10 putative alleles per individual, indicating at least the existence of 5 MHC I loci in the goose. The marked excess of the non-synonymous over the synonymous substitution in the peptide-binding region (PBR) along 27 alleles and five positively selected sites (PSSs) detected around the PBR indicated that balancing selection might be the major force in shaping high MHC variation in the goose. Additionally, IA alleles displaying lower polymorphism were subject to less positive selection pressure than non-IA alleles with a higher level of polymorphism. (MHC vertebrates Presently birds study AncyIE2*09/*11/*13/*21 AncyIE209111321 AncyIE Ancy IE2*09/*11/*13/*21 IE2 09 11 13 21 IE (Ancy-IE2*09/*11/*13/*21 combinations patterns nextgeneration next generation 6 310 3 10 3-1 individual nonsynonymous non peptidebinding peptide binding (PBR PSSs (PSSs Additionally nonIA AncyIE2 AncyIE2*09/*11/*13/*2 AncyIE20911132 IE209111321 IE2*09/*11/*13/*2 0 1 (Ancy-IE2*09/*11/*13/*2 31 3- AncyIE2*09/*11/*13/* AncyIE2091113 IE20911132 IE2*09/*11/*13/* (Ancy-IE2*09/*11/*13/* AncyIE2*09/*11/*13/ AncyIE209111 IE2091113 IE2*09/*11/*13/ (Ancy-IE2*09/*11/*13/ AncyIE2*09/*11/*13 AncyIE20911 IE209111 IE2*09/*11/*13 (Ancy-IE2*09/*11/*13 AncyIE2*09/*11/*1 AncyIE2091 IE20911 IE2*09/*11/*1 (Ancy-IE2*09/*11/*1 AncyIE2*09/*11/* AncyIE209 IE2091 IE2*09/*11/* (Ancy-IE2*09/*11/* AncyIE2*09/*11/ AncyIE20 IE209 IE2*09/*11/ (Ancy-IE2*09/*11/ AncyIE2*09/*11 IE20 IE2*09/*11 (Ancy-IE2*09/*11 AncyIE2*09/*1 IE2*09/*1 (Ancy-IE2*09/*1 AncyIE2*09/* IE2*09/* (Ancy-IE2*09/* AncyIE2*09/ IE2*09/ (Ancy-IE2*09/ AncyIE2*09 IE2*09 (Ancy-IE2*09 AncyIE2*0 IE2*0 (Ancy-IE2*0 AncyIE2* IE2* (Ancy-IE2* (Ancy-IE2 (Ancy-IE

Abstract Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models. prevalence misunderstood antidepressants some conditions heterogeneity genetics etiology decades (iPSC humanderived variance pharmaceuticals patientderived nonresponders non responders publications models

Abstract The sacred ayahuasca brew, utilized by indigenous communities in the Amazon and syncretic religious groups in Brazil, primarily consists of a decoction of two plants: (i) the Amazonian liana known as Mariri or Jagube (Banisteriopsis caapi), and (ii) the shrub referred as Chacrona or Rainha (Psychotria viridis). While Chacrona leaves are rich in N,N-Dimethyltryptamine (DMT), a potent psychedelic, the macerated vine of Mariri provides beta-carboline alkaloids acting as monoamine oxidase inhibitors, preventing DMT’s degradation. This study sequenced, assembled, and analyzed the complete genome of B. caapi’s mitochondrion, yielding a circular structure spanning 503,502 bp. Although the mtDNA encompasses most plant mitochondrial genes, it lacks some ribosomal genes, presents some atypical genes, and contains plastid pseudogenes, suggesting gene transfer between organelles. The presence of a 7-Kb repetitive segment containing copies of the rrnL and trnfM genes suggests mitogenome isomerization, supporting the hypothesis of dynamic mitogenome maintenance in plants. Phylogenetics and phylogenomics across 24 Malpighiales confirms the sample’s placement in the “Tucunacá” ethnovariety, aligning with morphological identification. This study spearheads efforts to decode the genome of this esteemed Malpighiaceae. brew Brazil plants i (i Banisteriopsis caapi, caapi , caapi) ii (ii Psychotria viridis. viridis . viridis) N,NDimethyltryptamine NNDimethyltryptamine N,N Dimethyltryptamine N DMT, DMT (DMT) psychedelic betacarboline beta carboline inhibitors DMTs s degradation sequenced assembled B caapis mitochondrion 503502 503 502 503,50 bp pseudogenes organelles 7Kb Kb 7 isomerization 2 samples sample Tucunacá “Tucunacá ethnovariety identification Malpighiaceae NDimethyltryptamine NN (DMT 50350 50 503,5 5035 5 503,

Abstract Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway. (CS RCC. RCC . (RCC) (RCSCs previously (SHH selfrenewal, selfrenewal self renewal, renewal self-renewal growth resistance metastasis CSCs. CSCs (CSCs) cancerrelated related ΔNpα ΔNp α tumors studies nonsmokers. nonsmokers non smokers. non-smokers assay Besides sphereforming forming Moreover CSinduced (RCC (CSCs

Abstract To explore the diversity of scenarios in nature, animals have evolved tools to interact with different environmental conditions. Chemoreceptors are an important interface component and among them, olfactory receptors (ORs) and gustatory receptors (GRs) can be used to find food and detect healthy resources. Drosophila is a model organism in many scientific fields, in part due to the diversity of species and niches they occupy. The contrast between generalists and specialists Drosophila species provides an important model for studying the evolution of chemoreception. Here, we compare the repertoire of chemoreceptors of different species of Drosophila with that of D. incompta, a highly specialized species whose ecology is restricted to Cestrum flowers, after reporting the preferences of D. incompta to the odor of Cestrum flowers in olfactory tests. We found evidence that the chemoreceptor repertoire in D. incompta is smaller than that presented by species in the Sophophora subgenus. Similar patterns were found in other non-Sophophora species, suggesting the presence of underlying phylogenetic trends. Nevertheless, we also found autapomorphic gene losses and detected some genes that appear to be under positive selection in D. incompta, suggesting that the specific lifestyle of these flies may have shaped the evolution of individual genes in each of these gene families. nature conditions them ORs (ORs GRs (GRs resources fields occupy chemoreception Here D tests subgenus nonSophophora non trends Nevertheless families

Abstract Dicliptera tinctoria is a member of Acanthaceae, which has a wide distribution and contains potentially medicinal species, and exhibited pharmaceutical potentials. This study sequenced and characterized the complete chloroplast genome of Dicliptera tinctoria. The newly sequenced cpDNA of D. tinctoria was 150,733 bp in length and had a typical quadripartite structure consisting of a large single copy (LSC, 82,895 bp), a small single copy (SSC, 17,249 bp), and two inverted repeat (IRs, 25,295 bp each) regions. This genome also contained 80 protein-coding genes, 30 transfer RNAs, and four ribosomal RNAs, which is identical to other chloroplast genomes in Acanthaceae family. Nucleotides diversity analysis among chloroplast genomes of Acanthaceae species revealed eight hypervariable regions, including trnK_UUU-matK, trnC_GCA-petN, accD, rps12-clpP, rps3-rps19, ycf1-ndhF, ccsA-ndhD, and ycf1. Phylogenetic analysis revealed the paraphyly of Dicliptera species and monophyly in four Acanthaceae subfamilies. These results provide an overview of genomic variations in Acanthaceae chloroplast genome, which is helpful for further genomic studies. potentials D 150733 150 733 150,73 LSC, LSC (LSC 82895 82 895 82,89 bp, , bp) SSC, SSC (SSC 17249 17 249 17,24 IRs, IRs (IRs 25295 25 295 25,29 each regions 8 proteincoding protein coding genes 3 RNAs family trnK_UUUmatK, trnKUUUmatK trnK_UUU matK, trnK UUU matK trnK_UUU-matK trnC_GCApetN, trnCGCApetN trnC_GCA petN, trnC GCA petN trnC_GCA-petN accD rps12clpP, rps12clpP rpsclpP rps12 clpP, clpP rps rps12-clpP rps3rps19, rps3rps19 rpsrps rps3 rps19, rps19 rps3-rps19 ycf1ndhF, ycf1ndhF ycfndhF ycf1 ndhF, ndhF ycf ycf1-ndhF ccsAndhD, ccsAndhD ccsA ndhD, ndhD ccsA-ndhD subfamilies studies 15073 15 73 150,7 8289 89 82,8 1724 1 24 17,2 2529 2 29 25,2 UUUmatK trnK_UUUmatK trnKUUU GCApetN trnC_GCApetN trnCGCA rps1 rps3rps1 rps3-rps1 1507 7 150, 828 82, 172 17, 252 25, rps3rps rps3-rps

Abstract Transplantation of stem cells derived from donors with CCR5Δ32 homozygous genotype is a potential strategy to achieve both the control of malignant hematological disease as well as sustained remission of the HIV infection, and researchers in different countries are looking for CCR5Δ32 homozygous donors to replicate such a ‘double-target’ strategy. We determined the frequency of the CCR5Δ32 variant in a sample of 1,398 bone marrow donors from Rio Grande do Sul State, Brazil. This study also evaluated whether HLA-A, HLA-B and HLA-DRB1 genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers in a population characterized by a significant genetic admixture. The CCR5Δ32 allele frequency was 7.4% (CI0.95 6.4-8.4%), and the frequency of the Δ32/Δ32 homozygous genotype was 0.72% (CI0.95 0.34-1.31%). In general, HLA genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers. Considering the large number of bone marrow donors in Brazil and the high CCR5Δ32 allele frequency observed in our study, our results clearly indicate the existence of a considerable amount of potential CCR5Δ32 homozygous bone marrow donors in southern Brazil, suggesting that an active search for these donors is not only feasible but an attractive and promising strategy towards effective HIV infection control and treatment. CCRΔ CCR Δ CCR5Δ3 ‘doubletarget doubletarget ‘double target double ‘double-target 1398 1 398 1,39 State HLAA, HLAA A, A HLA-A HLAB B HLADRB1 HLADRB DRB1 DRB HLA-DRB noncarriers non admixture 74 7 4 7.4 CI0.95 CI095 CI CI0 95 (CI0.9 6.48.4%, 6484 6.4 8.4% , 6 8 6.4-8.4%) Δ32Δ32 ΔΔ Δ32 Δ32/Δ3 072 0 72 0.72 0.341.31%. 034131 0.34 1.31% . 34 31 0.34-1.31%) general noncarriers. carriers. treatment CCR5Δ 139 39 1,3 7. CI0.9 CI09 9 (CI0. 48 6.48.4% 648 64 6. 84 8.4 6.4-8.4% Δ32Δ3 Δ3 Δ32/Δ 07 0.7 341 0.341.31% 03413 034 0.3 131 1.31 3 0.34-1.31% 13 1, CI0. (CI0 6.48.4 8. 6.4-8.4 Δ32Δ 0. 0.341.31 0341 03 1.3 0.34-1.31 (CI 6.48. 6.4-8. 0.341.3 1. 0.34-1.3 6.48 6.4-8 0.341. 0.34-1. 6.4- 0.341 0.34-1 0.34-

Abstract Chemotherapy stands out as the main systemic treatment strategy against cancer and still faces problems related to multidrug resistance and severe side effects. Copper-based drugs have been widely explored in medicinal chemistry, since copper is an essential metal for physiological activities with antineoplastic effects. In this context, the present study aimed to evaluate the recombinogenic/mutagenic and anticarcinogenic potential of the complex CBP-01 - [Cu(bta)(1,10-phen)ClO4] (Hbta = 4,4,4-trifluoro-1-phenyl-1,3-butanedione and 1,10-phen =1,10-phenanthroline) - through the Somatic and Recombination test (SMART) and the Epithelial Tumor Test (ETT) in Drosophila melanogaster, compared with carboplatin (CARB) and cisplatin (CIS) effects. According to our results, CARB and CIS induced a high frequency of mutant spots, which was not verified at higher concentrations of CBP-01. In addition, CBP-01 exhibited mutagenic/recombinogenic potential only at the lowest concentration and after biometabolization. Subsequently, in the ETT test, CBP-01 did not demonstrate carcinogenic effect. Lastly, epithelial tumors were identified in flies treated with CARB and CIS, which were modulated by the CBP-01 complex. Therefore, CBP-01 modulates genotoxicity of other compounds and is a promising metal-based drug for the development of a new anticancer agent or for optimization of therapeutic regimens. effects Copperbased Copper based chemistry context recombinogenicmutagenic recombinogenic mutagenic CBP01 CBP 01 CBP-0 Cubta1,10phenClO4 Cubta110phenClO4 CubtaphenClO Cu bta 1,10 phen ClO4 1 10 ClO [Cu(bta)(1,10-phen)ClO4 Hbta 4,4,4trifluoro1phenyl1,3butanedione 444trifluoro1phenyl13butanedione trifluorophenylbutanedione 4,4,4 trifluoro phenyl 1,3 butanedione 4 3 1,10phen 110phen =1,10phenanthroline 110phenanthroline phenanthroline =1,10 =1,10-phenanthroline SMART (SMART (ETT melanogaster (CARB (CIS results spots CBP01. 01. addition mutagenicrecombinogenic biometabolization Subsequently effect Lastly Therefore metalbased regimens CBP0 0 CBP- Cubta1 10phenClO4 Cubta phenClO Cubta1,10phenClO Cubta110phenClO 110 1,1 [Cu(bta)(1,10-phen)ClO 4trifluoro1phenyl1 3butanedione 444 4,4, 13 1, 10phen 10phenanthroline =1,1 10phenClO 11 trifluorophenyl 4trifluoro1phenyl 44 4,4 =1, 4, =1