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 Olive flounder (Paralichthys olivaceus), a popular aquaculture species, is plagued by the disease scuticociliatosis caused by Miamiensis avidus, which has a high mortality rate and is typically treated with chemicals such as formalin and hydrogen peroxide. However, Carpesii fructus extract has shown potential as a natural therapeutic agent by reducing the motility of M. avidus. However, despite its potential importance, the effect of the extract on fish metabolism remains unknown. In this study, the effect of Carpesii fructus extract and formalin on fish metabolism was analysed by whole transcriptome analysis in the liver of P. olivaceus. A total of 37,796 transcripts were generated and differential expression genes (DEGs) were identified in the liver of P. olivaceus treated with Carpesii fructus extract or formalin. In addition, functional analysis of DEGs between treatment groups was presented using Gene Ontology. These results will be crucial for the study of scuticociliatosis in various fish species, including P. olivaceus, and for the development of therapeutic agents for other diseases. Paralichthys , olivaceus) species avidus peroxide However M importance unknown P 37796 37 796 37,79 (DEGs addition Ontology diseases 3779 3 79 37,7 377 7 37,

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 Integrative network analysis (INA) is important for identifying gene modules or epigenetically regulated molecular pathways in diseases. This study evaluated the effect of excessive gestational weight gain (EGWG) on INA of differentially methylated regions, maternal metabolism and offspring growth. Brazilian women from “The Araraquara Cohort Study” with adequate pre-pregnancy body mass index were divided into EGWG (n=30) versus adequate gestational weight gain (AGWG, n=45) groups. The methylome analysis was performed on maternal blood using the Illumina MethylationEPIC BeadChip. Fetal-neonatal growth was assessed by ultrasound and anthropometry, respectively. Maternal lipid and glycemic profiles were investigated. Maternal triglycerides-TG (p=0.030) and total cholesterol (p=0.014); fetus occipito-frontal diameter (p=0.005); neonate head circumference-HC (p=0.016) and thoracic perimeter (p=0.020) were greater in the EGWG compared to the AGWG group. Multiple linear regression analysis showed that maternal DNA methylation was associated with maternal TG and fasting insulin, fetal abdominal circumference, and fetal and neonate HC. The DMRs studied were enriched in 142 biological processes, 21 molecular functions,and 17 cellular components with terms directed for the fatty acids metabolism. Three DMGMs were identified:COL3A1, ITGA4 and KLRK1. INA targeted chronic diseases and maternal metabolism contributing to an epigenetic understanding of the involvement of GWG in maternal metabolism and fetal-neonatal growth. (INA (EGWG regions Study prepregnancy pre pregnancy n=30 n30 n 30 (n=30 AGWG, (AGWG n=45 n45 45 groups BeadChip Fetalneonatal Fetal neonatal anthropometry respectively investigated triglyceridesTG triglycerides p=0.030 p0030 p 0 030 (p=0.030 p=0.014 p0014 014 (p=0.014) occipitofrontal occipito frontal p=0.005 p0005 005 (p=0.005) circumferenceHC circumference HC p=0.016 p0016 016 (p=0.016 p=0.020 p0020 020 (p=0.020 group insulin 14 processes 2 functionsand functions 1 identifiedCOL3A1, identifiedCOL3A1 identifiedCOLA identified COL3A1, COL3A1 COL A identified:COL3A1 ITGA KLRK1 KLRK fetalneonatal n=3 n3 3 (n=3 n=4 n4 4 p=0.03 p003 03 (p=0.03 p=0.01 p001 01 (p=0.014 p=0.00 p000 00 (p=0.005 (p=0.01 p=0.02 p002 02 (p=0.02 identifiedCOL identifiedCOL3A COLA COL3A identified:COL3A n= (n= p=0.0 p00 (p=0.0 (p=0.00 (n p=0. p0 (p=0. p=0 (p=0 p= (p= (p

Abstract People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes. pwCF (pwCF Fdel F del phenotypes A455E AE A E L206W LW L W (CF Nutritional cohort Twohundred Two hundred included subgroups F508delF508del FdelFdel n=149 n149 n 149 (n=149) F508del6211GT FdelGT 621 1G T G n=17 n17 17 (n=17) F508del7111GT 711 n=11 n11 11 (n=11) F508delA455E FdelAE n=12 n12 12 (n=12) F508delL206W FdelLW n=14. n14 n=14 . 14 (n=14) p<0.0001, p00001 p p<0.0001 , 0 0001 (p<0.0001) AUC (AUC p=0.027. p0027 p=0.027 027 (p=0.027) p<0.001. p0001 p<0.001 001 (p<0.001) FEV1 FEV (FEV1 p<0.0001. 737 7 37 7.3 years groups sufficiency status CFrelated related Diabetes delF (n=149 GT 62 n=1 n1 1 (n=17 71 (n=11 delA (n=12 delL (n=14 p0000 p<0.000 000 (p<0.0001 p002 p=0.02 02 (p=0.027 p000 p<0.00 00 (p<0.001 (FEV 73 3 7. 6 n= (n=1 (p<0.000 p00 p=0.0 (p=0.02 p<0.0 (p<0.00 (n= p0 p=0. (p=0.0 p<0. (p<0.0 (n p=0 (p=0. p<0 (p<0. p= (p=0 p< (p<0 (p= (p< (p

Abstract Centromochlinae is a widely diverse subfamily with more than 50 species and several taxonomic conflicts due to morphological similarity between Tatia and Centromochlus species. However, cytogenetic studies on this group have been limited to only four species so far. Therefore, here we present the karyotype of Centromochlus schultzi from the Xingu River in Brazil using classic cytogenetic techniques, physical mapping of the 5S and 18S rDNAs, and telomeric sequences (TTAGGG)n. The species had 58 chromosomes, simple NORs and 18S rDNA sites. Heterochromatic regions were detected on the terminal position of most chromosomes, including pericentromeric and centromeric blocks that correspond to interstitial telomeric sites. The 5S rDNA had multiple sites, including a synteny with the 18S rDNA in the pair 24st, which is an ancestral feature for Doradidae, sister group of Auchenipteridae, but appears to be a homoplastic trait in this species. So far, C. schultzi is only the second species within Centromochlus to be karyotyped, but it has already presented characteristics with great potential to assist in future discussions on taxonomic issues in the subfamily Centromochlinae, including the first synteny between rDNAs in Auchenipteridae and also the presence of heterochromatic ITSs that could represent remnants of ancient chromosomal fusions. 5 However far Therefore techniques S TTAGGGn. TTAGGGn TTAGGG n. n (TTAGGG)n chromosomes sites 24st st Doradidae C karyotyped fusions

Abstract We announce the mitochondrial genomes of seven species of the genus Sporophila (S. bouvreuil, S. iberaensis, S. melanogaster, S. minuta, S. nigrorufa, S. pileata, and S. ruficollis) which were validated by comparative genomic and phylogenetic analysis with related species. The mitochondrial genomes of seven passerines of the genus Sporophila were assembled (three complete and four nearly complete genomes) and were validated by reconstructing phylogenetic relations within Thraupidae. The complete mitogenomes ranged from 16,781 bp in S. ruficollis to 16,791 bp in S. minuta. We identified a conserved genome composition within all mitogenomes with 13 protein-coding genes, 22 tRNAs and two rRNAs. We observed a bias in the nucleotide composition and six mutational hotspots in Sporophila mitogenomes. Our mitogenome-based phylogenetic tree has S. minuta, S. maximiliani and S. nigricollis as sister species of the remaining species in the genus. We present new mitogenome sequences for seven Sporophila species, providing new genomic resources that may be useful for research on the evolution, comparative genetics, and conservation of this threatened group. S (S bouvreuil iberaensis melanogaster minuta nigrorufa pileata three Thraupidae 16781 16 781 16,78 16791 791 16,79 1 proteincoding protein coding genes 2 rRNAs mitogenomebased based evolution genetics group 1678 78 16,7 1679 79 167 7 16,

Abstract Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor β-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2’s impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients. (GC treatment βbinding β binding LTBP (LTBP2 understood LTBP2s LTBPs s lines assays Lentivirusmediated Lentivirus mediated HGC27 HGC 27 HGC-2 NFκB2/Bcl3/cyclin NFκB2Bcl3cyclin NFκBBclcyclin NF κB2/Bcl 3/cyclin κB2 Bcl 3 cyclin κB D Additionally NFκB LTBP2silenced LTBPsilenced silenced HGC27/DDPR HGC27DDPR HGCDDPR 27/DDPR DDPR p52/Bcl3/cyclin p52Bcl3cyclin pBclcyclin p52/Bcl p52 p conclusion patients (LTBP HGC2 2 HGC- Bcl3 κB2Bcl κBBcl 3cyclin 27DDPR p52Bcl pBcl p5

Abstract Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA. (LatAm welldocumented well documented disorders However Here genedisease gene disease . (NGDA) genomics patients people scientists LatAms s (NGDA

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines. alphaNacetylglucosaminidase, alphaNacetylglucosaminidase alpha N acetylglucosaminidase, acetylglucosaminidase alpha-N-acetylglucosaminidase sulphate features 1 Brazil 72 7 2 7. identified 23 3 2- aggressiveness four decade walk Furthermore progresses 50 organomegaly problems systems guidelines 5

Abstract Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients’ health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs. drug cells However lowdose low dose unclear subtherapeutic sub (ERα MCF7 MCF 7 MCF- RTqPCR, RTqPCR RT qPCR, qPCR RT-qPCR blot woundhealing wound healing immunoprecipitation 01 0 1 (0. 02 2 0. ESR1 ESR TFF1 TFF genes levels Moreover estrogenindependent independent pS NCoR patients health receptorpositive positive tumors Subtherapeutic Sub processes butyratemediated mediated activation drugs (0 (

Abstract Group I introns are small RNAs (250-500 nt) capable of catalyzing their own splicing from the precursor RNA. They are widely distributed across the tree of life and have intricate relationships with their host genomes. In this work, we review its basic structure, self-splicing and its mechanisms of gene mobility. As they are widely found in unicellular eukaryotes, especially fungi, we gathered information regarding their possible impact on the physiology of fungal cells and the possible application of these introns in medical mycology. 250500 250 500 (250-50 nt RNA genomes work structure selfsplicing self mobility eukaryotes fungi mycology 25050 25 50 (250-5 2505 2 5 (250- (250 (25 (2 (

Abstract Genomic effect variants associated with survival and protection against complex diseases vary between populations due to microevolutionary processes. The aim of this study was to analyse diversity and distribution of effect variants in a context of potential positive selection. In total, 475 individuals of Lithuanian origin were genotyped using high-throughput scanning and/or sequencing technologies. Allele frequency analysis for the pre-selected effect variants was performed using the catalogue of single nucleotide polymorphisms. Comparison of the pre-selected effect variants with variants in primate species was carried out to ascertain which allele was derived and potentially of protective nature. Recent positive selection analysis was performed to verify this protective effect. Four variants having significantly different frequencies compared to European populations were identified while two other variants reached borderline significance. Effect variant in SLC30A8 gene may potentially protect against type 2 diabetes. The existing paradox of high rates of type 2 diabetes in the Lithuanian population and the relatively high frequencies of potentially protective genome variants against it indicate a lack of knowledge about the interactions between environmental factors, regulatory regions, and other genome variation. Identification of effect variants is a step towards better understanding of the microevolutionary processes, etiopathogenetic mechanisms, and personalised medicine. processes total 47 highthroughput throughput andor or technologies preselected pre selected polymorphisms nature significance SLCA SLC A SLC30A factors regions variation mechanisms medicine 4

Abstract Pathogenic DNA alterations in GJB2 are present in nearly half of non-syndromic hearing loss cases with autosomal recessive inheritance. The most frequent variant in GJB2 causing non-syndromic hearing loss is the frameshifting c.35del. GJB2 encodes Cx26, a protein of the connexin family that assembles hemichannels and gap junctions. The expression of paralogous proteins is believed to compensate for the loss of function of specific connexins. As Cx26 has been involved in cell differentiation in distinct tissues, we employed stem cells derived from human exfoliated deciduous teeth (SHEDs), homozygous for the c.35del variant, to assess GJB2 roles in stem cell differentiation and the relationship between its loss of function and the expression of paralogous genes. Primary SHED cultures from patients and control individuals were compared. SHEDs from patients had significantly less GJB2 mRNA and increased amount of GJA1 (Cx43), but not GJB6 (Cx30) or GJB3 (Cx31) mRNA. In addition, they presented higher induced differentiation to adipocytes and osteocytes but lower chondrocyte differentiation. Our results suggest that GJA1 increased expression may be involved in functional compensation for GJB2 loss of function in human stem cells, and it may explain changes in differentiation properties observed in SHEDs with and without the c.35del variant. GJB nonsyndromic non syndromic inheritance c35del cdel c 35del del Cx junctions connexins Cx2 tissues SHEDs, , (SHEDs) genes compared GJA Cx43, Cx43 (Cx43) Cx30 (Cx30 Cx31 (Cx31 addition (SHEDs Cx4 (Cx43 Cx3 (Cx3 (Cx4 (Cx

Abstract High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology. However unclear LDSC (LDSC ρHESS ρ HESS (ρ-HESS correlations MiXeR (MiXeR overlap Then stratifiedLDSC stratified SLDSC S (S-LDSC Meanwhile SNP (SNP 13 5 rg=0.21. rg021 rg rg=0.21 . 0 21 (rg=0.21) 04 4 0. 28 2 8 2. variants mammary uterus tissues Moreover 7 death comorbidity. comorbidity co morbidity. morbidity co-morbidity Ultimately etiology 1 rg02 rg=0.2 (rg=0.21 rg0 rg=0. (rg=0.2 rg=0 (rg=0. rg= (rg=0 (rg= (rg