Abstract Comprehensive protein-protein interaction (PPI) maps are critical for understanding the functional organization of the proteome, but challenging to produce experimentally. Here, we developed a computational method for predicting PPIs based on protein docking. Evaluation of performance on benchmark sets demonstrated the ability of the docking-based method to accurately identify PPIs using predicted protein structures. By employing the docking-based method, we constructed a structurally resolved PPI network consisting of 24,653 interactions between 2,131 proteins, which greatly extends the current knowledge on the rice protein-protein interactome. Moreover, we mapped the trait-associated single nucleotide polymorphisms (SNPs) to the structural interactome, and computationally identified 14 SNPs that had significant consequences on PPI network. The protein structural interactome map provided a resource to facilitate functional investigation of PPI-perturbing alleles associated with agronomically important traits in rice. proteinprotein (PPI proteome experimentally Here docking dockingbased structures 24653 24 653 24,65 2131 2 131 2,13 proteins Moreover traitassociated trait (SNPs 1 PPIperturbing perturbing 2465 65 24,6 213 13 2,1 246 6 24, 21 2,

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 In phytophagous insects, adaptation to a new host is a dynamic process, in which early and later steps may be underpinned by different features of the insect genome. Here, we tested the hypothesis that early steps of this process are underpinned by a shift in gene expression patterns. We set up a short-term artificial selection experiment (10 generations) for the use of an alternative host (Cicer arietinum) on populations of the bean beetle Zabrotes subfasciatus. Using Illumina sequencing on young adult females, we show the selected populations differ in the expression of genes associated to stimuli, signalling, and developmental processes. Particularly, the “C. arietinum” population shows upregulation of histone methylation genes, which may constitute a strategy for fine-tuning the insect global gene expression network. Using qPCR on body regions, we demonstrated that the “Phaseolus vulgaris” population upregulates the genes polygalacturonase and egalitarian and that the expression of an odorant receptor transcript variant changes over generations. Moreover, in this population we detected the existence of vitellogenin (Vg) variants in both males and females, possibly harbouring canonical reproductive function in females and extracellular unknown functions in males. This study provides the basis for future genomic investigations seeking to shed light on the nature of the proximate mechanisms involved in promoting differential gene expression associated to insect development and adaptation to new hosts. insects genome Here patterns shortterm short term 10 (1 generations Cicer arietinum subfasciatus stimuli signalling processes Particularly C. C “C finetuning fine tuning network regions Phaseolus vulgaris Moreover Vg (Vg hosts 1 (

Abstract Delimiting species is challenging in recently diverged species, and adaptive radiation is fundamental to understanding the evolutionary processes because it requires multiple ecological opportunities associated with adaptation to biotic and abiotic environments. The young Petunia genus (Solanaceae) is an excellent opportunity to study speciation because of its association with pollinators and unique microenvironments. This study evaluated the phylogenetic relationships among a Petunia clade species with different floral syndromes that inhabit several environments. We based our work on multiple individuals per lineage and employed nuclear and plastid phylogenetic markers and nuclear microsatellites. The phylogenetic tree revealed two main groups regarding the elevation of the distribution range, whereas microsatellites showed high polymorphism-sharing splitting lineages into three clusters. Isolation by distance, migration followed by new environment colonization, and shifts in floral syndrome were the motors for lineage differentiation, including infraspecific structuring, which suggests the need for taxonomic revision in the genus. environments Solanaceae (Solanaceae microenvironments range polymorphismsharing polymorphism sharing clusters distance colonization differentiation structuring

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 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 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 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 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 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 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 To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment. Peg Peg1 LPSinduced LPS induced T RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR HMGB (HMGB1 interleukin6 interleukin 6 interleukin- IL6 IL (IL-6 ELISA 4 3 downregulation down regulation mice Moreover IL- suppression context subjects Creactive C reactive CRP, CRP , (CRP) ESR (ESR treatment (HMGB (IL- (CRP (IL

Abstract Senescence is a cellular state in which the cell loses its proliferative capacity, often irreversibly. Physiologically, it occurs due to a limited capacity of cell division associated with telomere shortening, the so-called replicative senescence. It can also be induced early due to DNA damage, oncogenic activation, oxidative stress, or damage to other cellular components (collectively named induced senescence). Tumor cells acquire the ability to bypass replicative senescence, thus ensuring the replicative immortality, a hallmark of cancer. Many anti-cancer therapies, however, can lead tumor cells to induced senescence. Initially, this response leads to a slowdown in tumor growth. However, the longstanding accumulation of senescent cells (SnCs) in tumors can promote neoplastic progression due to the enrichment of numerous molecules and extracellular vesicles that constitutes the senescence-associated secretory phenotype (SASP). Among other effects, SASP can potentiate or unlock the tumor plasticity and phenotypic transitions, another hallmark of cancer. This review discusses how SnCs can fuel mechanisms that underlie cancer plasticity, like cell differentiation, stemness, reprogramming, and epithelial-mesenchymal transition. We also discuss the main molecular mechanisms that make SnCs resistant to cell death, and potential strategies to target SnCs. At the end, we raise open questions and clinically relevant perspectives in the field. irreversibly Physiologically shortening socalled so called senescence activation stress collectively . senescence) immortality anticancer anti therapies however Initially growth However (SnCs senescenceassociated SASP. (SASP) effects transitions differentiation stemness reprogramming epithelialmesenchymal epithelial mesenchymal transition death end field (SASP