Cytoplasmic Gene Research Articles

Prognostic Impact of Blood MN1 Copy Numbers Before Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia.

High expression of the leukemia-associated gene meningioma-1 (MN1) is frequently found at diagnosis of acute myeloid leukemia (AML) and associates with adverse outcomes. The presence of measurable residual disease (MRD) in complete remission (CR) indicates high risk of relapse and worse outcome in AML patients. However, the prognostic impact of MN1 expression levels as MRD marker has not been evaluated. Digital droplet polymerase chain reaction (ddPCR) is a novel technique allowing sensitive and specific absolute gene expression quantification. We retrospectively analyzed 124 AML patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in CR or CR with incomplete peripheral recovery. Absolute MN1 copy numbers in peripheral blood were assessed prior to HSCT (median 7; range 0-29 days) using ddPCR. High pre-HSCT MN1/Abelson murine leukemia viral oncogene homolog 1 gene (ABL1) copy numbers associated with a higher cumulative incidence of relapse after HSCT and-in relapsing patients-shorter time to relapse. In multivariable analysis, high pre-HSCT MN1/ABL1 copy numbers remained an independent prognosticator for relapse after HSCT. Patients with the highest pre-HSCT MN1/ABL1 copy numbers also had the highest risk of relapse. MN1 copy number assessment also added prognostic information to nucleophosmin 1 gene (NPM1) mutation- and brain and acute leukemia, cytoplasmic (BAALC) and Wilm's tumor gene 1 (WT1) expression-based MRD evaluation. Our study demonstrates the feasibility of the novel ddPCR technique for MN1/ABL1 copy number assessment as a marker for MRD. Evaluation of MN1/ABL1 copy numbers allows the identification of patients at high risk of relapse, independently of other diagnostic risk factors and MRD markers.

Eucalyptus grandis THIOREDOXINS, DIVERSITY AND GENE EXPRESSION

ABSTRACT Tree genomes have been sequenced in recent years providing a source of basic information on multigenic family characterization. Comparative genomics based on those complete genome sequences available in public database is an important tool providing useful information to progress on functional gene characterization. In this work, we focus on gene encoding for Thioredoxins (Trxs) in Eucalyptus grandis genome, which are oxidoreductase enzymes, involved in significant biochemical processes, above all the maintenance of cellular homeostasis. Here we investigate the diversity, structure and expression of these genes in eucalyptus. For this purpose, bioinformatics tools were employed, using public platforms data, to identify coding sequences and validate gene expression. Specific softwares were employed to characterize gene structure and expression. RT-PCR assays were carried out to specifically verify the expression of 4 cytoplasmic thioredoxin genes, observed in silico from leaf, phloem, xylem and apical meristem tissues. Twenty-two Trxs with characteristic and canonic active sites were identified, confirming the presence of all types of the three main groups already defined as plastidial (m, f, x, y, z) cytoplasmatic (h) and mitochondrial (o). However, differences in the number of genes per group were observed when compared with other tree genomes. The expression of these thioredoxin genes compared to some homologous genes presented divergent expression patterns compared to Arabidopis thaliana suggesting a functional specificity in eucalyptus, such as in the case of Eucgr.F01604 gene encoding an h1 cytoplasmic Trx, which presents a strong expression in conductor tissues.

View from an mRNP: The Roles of SR Proteins in Assembly, Maturation and Turnover.

Serine- and arginine-rich proteins (SR proteins) are a family of multitasking RNA-binding proteins (RBPs) that are key determinants of messenger ribonucleoprotein (mRNP) formation, identity and fate. Apart from their essential functions in pre-mRNA splicing, SR proteins display additional pre- and post-splicing activities and connect nuclear and cytoplasmic gene expression machineries. Through changes in their post-translational modifications (PTMs) and their subcellular localization, they provide functional specificity and adjustability to mRNPs. Transcriptome-wide UV crosslinking and immunoprecipitation (CLIP-Seq) studies revealed that individual SR proteins are present in distinct mRNPs and act in specific pairs to regulate different gene expression programmes. Adopting an mRNP-centric viewpoint, we discuss the roles of SR proteins in the assembly, maturation, quality control and turnover of mRNPs and describe the mechanisms by which they integrate external signals, coordinate their multiple tasks and couple subsequent mRNA processing steps.

Inheritance pattern of fire blight resistance in pear

Fire blight caused by Erwinia amylovora is a serious disease that directly affects pear agriculture and production around the world. The most effective way to struggle with disease is develop new varieties and rootstocks. In this study, for a better understanding of the genetic base of fire blight such as heritability of disease resistance, breeding values of parents and maternal effect were investigated on F1 hybrid pear population. According to results, disease resistance shows polygenic inheritance and multiple factors were effective in heredity. Resistance to disease is transmitted to next generations by both parents. However, the influence of the female parent on inheritance is much greater than pollinator. ‘Magness’ and ‘Mustafa Bey’ varieties were found more effective for the transmission of disease resistance as female parents to next progenies. Similar results were obtained from ‘Kiefer’ and ‘Limon’ as pollinator. In addition to the importance of the parents exclusively in disease resistance, gene interactions between the parents also had a significant effect on this matter. Heritability of fire blight that was calculated from the non-additive genes was 23%, likewise 32% was calculated from additive genes. Broad-sense heritability of fire blight, representing the sum of this two situations was 55%. Maternal gene effects were greater than the pollinator and maternal effect had a 7% effect on the disease resistance, indicating that the cytoplasmic gene effects had important roles in the resistance. Obtained results will form basis for the development of new varieties that become resistant to fire blight by hybridization.

Antioxidant hesperetin improves the quality of porcine oocytes during aging in vitro.

The citrus flavonoid hesperetin has a variety of pharmacological actions, including antioxidant, antiinflammatory, and anticancer activities. This study investigated whether hesperetin prevents aging of oocytes in vitro in which it determined the maturation of nuclear and cytoplasm and the developmental capacity of embryo by modulating the reactive oxygen species (ROS) level. Porcine oocytes were matured in vitro for 44 hr (control) and for an additional 24 hr in the presence of 0, 1, 10, 100, and 250 μM hesperetin (aging, H-1, H-10, H-100, and H-250, respectively). Although there was no difference in the rate of maturation among all the groups, both the control and H-100 groups significantly increased in the rate of cleavage and blastocyst formation compared to the aging group. The H-100 group significantly decreased ROS activity and increases the level of glutathione (GSH) and expression of the antioxidant genes (PRDX5, NFE2L, SOD1, and SOD2) compared with the aging group. The H-100 groups prevented aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase and increased the messenger RNA expression of cytoplasmic maturation factor genes (GDF9, CCNB1, BMP15, and MOS). Subsequently, both the control and H-100 groups significantly increased the total cell number and decreased the apoptosis cells at the blastocyst stage compared with aging group. The results indicate that hesperetin improves the quality of porcine oocytes by protecting them against oxidative stress during aging in vitro.

Exposure to the lampricide TFM elicits an environmental stress response in yeast.

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is used to control sea lamprey populations in the Great Lakes and Lake Champlain. Little is known about the effects of this pesticide on gene expression in eukaryotic species. This study used microarray analysis to determine the effects of short term, high dose TFM exposure on gene expression in Saccharomyces cerevisiae. Yeast grown in standard glucose-containing media showed significant variation in gene expression in pathways related to cytoplasmic translation with the majority of these genes being downregulated. These findings were supported by the analysis of a similar but glucose-free experiment revealing that these cytoplasmic translation genes, mostly ribosomal subunit expressing genes, were similarly downregulated. The repression of the ribosomal subunit genes suggests that TFM exposure, regardless of glucose availability, evokes features of the environmental stress response in yeast.

The comparison of four mitochondrial genomes reveals cytoplasmic male sterility candidate genes in cotton

BackgroundThe mitochondrial genomes of higher plants vary remarkably in size, structure and sequence content, as demonstrated by the accumulation and activity of repetitive DNA sequences. Incompatibility between mitochondrial genome and nuclear genome leads to non-functional male reproductive organs and results in cytoplasmic male sterility (CMS). CMS has been used to produce F1 hybrid seeds in a variety of plant species.ResultsHere we compared the mitochondrial genomes (mitogenomes) of Gossypium hirsutum sterile male lines CMS-2074A and CMS-2074S, as well as their restorer and maintainer lines. First, we noticed the mitogenome organization and sequences were conserved in these lines. Second, we discovered the mitogenomes of 2074A and 2074S underwent large-scale substitutions and rearrangements. Actually, there were five and six unique chimeric open reading frames (ORFs) in 2074A and 2074S, respectively, which were derived from the recombination between unique repetitive sequences and nearby functional genes. Third, we found out four chimeric ORFs that were differentially transcribed in sterile line (2074A) and fertile-restored line.ConclusionsThese four novel and recombinant ORFs are potential candidates that confer CMS character in 2074A. In addition, our observations suggest that CMS in cotton is associated with the accelerated rates of rearrangement, and that novel expression products are derived from recombinant ORFs.

Comparative systematics and phylogeography of Quercus Section Cerris in western Eurasia: inferences from plastid and nuclear DNA variation.

Oaks (Quercus) comprise more than 400 species worldwide and centres of diversity for most sections lie in the Americas and East/Southeast Asia. The only exception is the Eurasian sect. Cerris that comprises about 15 species, most of which are confined to western Eurasia. This section has not been comprehensively studied using molecular tools. Here, we assess species diversity and provide a first comprehensive taxonomic and phylogeographic scheme of western Eurasian members of sect. Cerris using plastid (trnH-psbA) and nuclear (5S-IGS) DNA variation with a dense intra-specific and geographic sampling. Chloroplast haplotypes primarily reflected phylogeographic patterns originating from interspecific cytoplasmic gene flow within sect. Cerris and its sister section Ilex. We identified two widespread and ancestral haplotypes, and locally restricted derived variants. Signatures shared with Mediterranean species of sect. Ilex, but not with the East Asian Cerris oaks, suggest that the western Eurasian lineage came into contact with Ilex only after the first (early Oligocene) members of sect. Cerris in Northeast Asia had begun to radiate and move westwards. Nuclear 5S-IGS diversification patterns were more useful for establishing a molecular-taxonomic framework and to reveal hybridization and reticulation. Four main evolutionary lineages were identified. The first lineage is comprised of Q. libani, Q. trojana and Q. afares and appears to be closest to the root of sect. Cerris. These taxa are morphologically most similar to the East Asian species of Cerris, and to both Oligocene and Miocene fossils of East Asia and Miocene fossils of western Eurasia. The second lineage is mainly composed of the widespread Q. cerris and the narrow endemic species Q. castaneifolia, Q. look, and Q. euboica. The third lineage comprises three Near East species (Q. brantii, Q. ithaburensis and Q. macrolepis), well adapted to continental climates with cold winters. The forth lineage appears to be the most derived and comprises Q. suber and Q. crenata. Q. cerris and Q. trojana displayed high levels of variation; Q. macrolepis and Q. euboica, previously treated as subspecies of Q. ithaburensis and Q. trojana, likely deserve independent species status. A trend towards inter-specific crosses was detected in several taxa; however, we found no clear evidence of a hybrid origin of Q. afares and Q. crenata, as currently assumed.

Genetic control of in vitro morphogenesis in wild strawberry (Fragaria vesca)

AbstractIn vitro morphogenetic potential is a polygenic trait. Polygenes determining this trait can be located in the nuclear and cytoplasmic DNA. In this research, the role of nuclear and cytoplasmic genes in a genetic control of in vitro morphogenesis in Fragaria vesca L. (wild strawberry) was investigated. The study included 4 wild strawberry cultivars, that is, ‘Regina’, ‘Rugia’, ‘Yellow Wonder’ and ‘Baron Solemacher’. The 3rd Griffing method of diallel crossing was useful for achieving the purpose of the research, because it allowed to determine the possible influence of cytoplasmic loci on the inheritance of morphogenetic potential in the cultivars analysed. The cv. ‘Baron Solemacher’ revealed the maternal influence on the inheritance of morphogenetic potential in vitro. The impact of nuclear genes on the morphogenetic potential was recorded for the cv. ‘Yellow Wonder’. In cvs., ‘Regina’ and ‘Rugia’ the influence of both cytoplasmic and nuclear genes on the inheritance of morphogenetic abilities in vitro were observed, which depended on the specific interaction between the maternal plasmotype and the paternal nuclear genes.

Comparative analysis of circular RNAs between soybean cytoplasmic male-sterile line NJCMS1A and its maintainer NJCMS1B by high-throughput sequencing

BackgroundCytoplasmic male sterility (CMS) is a natural phenomenon of pollen abortion caused by the interaction between cytoplasmic genes and nuclear genes. CMS is a simple and effective pollination control system, and plays an important role in crop heterosis utilization. Circular RNAs (circRNAs) are a vital type of non-coding RNAs, which play crucial roles in microRNAs (miRNAs) function and post-transcription control. To explore the expression profile and possible functions of circRNAs in the soybean CMS line NJCMS1A and its maintainer NJCMS1B, high-throughput deep sequencing coupled with RNase R enrichment strategy was conducted.ResultsCircRNA libraries were constructed from flower buds of NJCMS1A and its maintainer NJCMS1B with three biological replicates. A total of 2867 circRNAs were identified, with 1009 circRNAs differentially expressed between NJCMS1A and NJCMS1B based on analysis of high-throughput sequencing. Of the 12 randomly selected circRNAs with different expression levels, 10 showed consistent expression patterns based on high-throughput sequencing and quantitative real-time PCR analyses. Tissue specific expression patterns were also verified with two circRNAs by quantitative real-time PCR. Most parental genes of differentially expressed circRNAs were mainly involved in biological processes such as metabolic process, biological regulation, and reproductive process. Moreover, 83 miRNAs were predicted from the differentially expressed circRNAs, some of which were strongly related to pollen development and male fertility; The functions of miRNA targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the target mRNAs were significantly enriched in signal transduction and programmed cell death. Furthermore, a total of 165 soybean circRNAs were predicted to contain at least one internal ribosome entry site (IRES) element and an open reading frame, indicating their potential to encode polypeptides or proteins.ConclusionsOur study indicated that the circRNAs might participate in the regulation of flower and pollen development, which could provide a new insight into the molecular mechanisms of CMS in soybean.

Inheritance of germination vigour in sugar beet sterility maintainers and their diallel hybrids

Aim. To determine the degree of dominance of the “seed germination” sign and combination ability of sterility maintainers using diallel analysis. Methods. Hybridization of sterility maintainers was arranged as diallel crosses. Genetic determination of the sign was determined in accordance with Heyman’s method. Results. Used in crossing sterility maintainer lines have been studied in terms of their productivity in previous variety tests. D. The dominant inheritance of “seed germination” sign in diallel hybrids was determined as following: in the structure of the sign variability 43 % of cross combinations inherited this sign as positive dominance. Genetic determination of the “synergy of germination” sign was determined by the effects of combination ability. The additive effect of the female parent was assessed at 18.4 %, in male parent at 18.1 %, while the nonadditive effect of interaction between the components was at 40.7 % The influence of cytoplasmic effects amounted to 22,7 %. Selected were the best lines in specific pairs; their genetic value was studied as the average value of heterosis in many crossings involving specific lines. Conclusions. When forming sources of improved signs it is advisable to consider the cytoplasmic gene effects, which share is estimated at 22.7 %. The best lines in terms of general combination ability for seed germination found to be sterility maintainers Ot 1 and Ot 2.
 Keywords: sterility maintainers, combination ability, seed germination, additive, non-additive, and reciprocal effects.

Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells

In mammals, gene silencing by the RNA-induced silencing complex (RISC) is a well-understood cytoplasmic posttranscriptional gene regulatory mechanism. Here, we show that embryonic stem cells (ESCs) contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO protein activity allows for the onset of differentiation. In the nucleus, AGO proteins interact with core RISC components, including the TNRC6 proteins and the CCR4-NOT deadenylase complex. In contrast to cytoplasmic miRNA-mediated gene silencing that mainly operates on cis-acting elements in mRNA 3' untranslated (UTR) sequences, in the nucleus AGO binding in the coding sequence and potentially introns also contributed to post-transcriptional gene silencing. Thus, nuclear localization of AGO proteins in specific cell types leads to a previously unappreciated expansion of the miRNA-regulated transcriptome.

The mitochondrial genome of an asymmetrically cell-fused rapeseed, Brassica napus, containing a radish-derived cytoplasmic male sterility-associated gene.

Cytoplasmic male sterility (CMS) is an agronomically important trait whose causative genes are located in the mitochondrial genome. A CMS rapeseed, Brassica napus 'SW18', was made 25 years ago by an asymmetric (or "donor-recipient") cell fusion between B. napus 'Westar' and a CMS radish (Raphanus sativus 'Kosena'), in order to transfer the radish CMS-associated gene without disturbing the rapeseed features. Here, we determined the nucleotide sequences of the mitochondrial genomes of Kosena radish and SW18. SW18 has a recombinant mitochondrial genome, which includes the whole 222-kb genome of Westar (54 genes) and a total of 23 kb insertions of four fragments from Kosena radish (three genes: orf125, trnfM and atp1). All of the Kosena radish-derived fragments in the SW18 mitochondrial genome had sequences at their ends (ranging from 63 bp to 628 bp) that are identical to the sequences at the sites of insertion on the Westar rapeseed-derived mitochondrial genome. This suggests that these insertions were mediated by homologous recombination. These results confirm at the nucleotide level that a desired CMS-associated gene (orf125) along with a few extraneous genes from radish were successfully transferred.

PO-147 Pinostilbene hydrate suppresses human oral cancer cell metastasis via downregulation matrix metalloproteinase-2 through the mitogen-activated protein kinase signalling pathway

IntroductionAcute myeloid leukaemia (AML) is the most common acute leukaemia in adults and has one of the poorest survival rates of all cancers. Despite advancements in treatments, the 5 year survival rate for AML remains at 26%, and is less than 8% for patients aged over 60. Approximately one-third of patients exhibit primary refractory disease, however, the mechanisms controlling this have not been fully elucidated. Overexpression of the brain and acute leukaemia, cytoplasmic (BAALC) gene is a negative prognostic factor for AML and is associated with primary refractory disease, but precisely how overexpression of BAALC is controlling sensitivity to chemotherapeutics is unknown. As AML cells with perturbations in DNA repair pathways exhibit alterations in sensitivity/resistance to a range of chemotherapeutics, we examined whether BAALC overexpression perturbs DNA repair pathways in AML cells.Material and methodsBAALC was overexpressed in a panel of AML cells and their ability to repair DNA damage was measured by western blot and comet assay. Alterations in expression of key DNA damage repair genes were measured by PCR in BAALC overexpressing and empty vector (EV) control cells. BAALC-mediated signalling complexes involved in DNA repair were identified by immunoprecipitation.Results and discussionsBAALC, but not EV, overexpression resulted in elevated DNA fragmentation (comet assay), and sustained gH2AX and ATM activation (pSer1981) post-daunorubicin and etoposide-induced DNA damage, indicative of an inability to repair the damage. Gene expression analyses in BAALC overexpressing cells identified that the expression of components (RAD51D, TP53BP1, BTG2) of the high-fidelity homologous recombination double strand break repair pathway were significantly decreased. Furthermore, BAALC interacts with several proteins (RAD51, CaMKII, dermcidin) implicated in DNA repair. Further supporting a role for BAALC overexpression in inducing defective homologous recombination repair, BAALC overexpressing AML cells were hypersensitive to cisplatin treatment.ConclusionAs perturbations in DNA repair pathways in AML have been associated with increased resistance to a range of chemotherapeutics, and BAALC overexpression is associated with primary refractory AML, our data suggests that BAALC overexpression induces decreased chemosensitivity by perturbing DNA repair pathways.

Abstract 532: PELP1 and AIB1 (SRC-3) complexes promote cancer stem cell-associated phenotypes in ER+ breast cancer models

Abstract Proline, glutamic acid, and leucine rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, we sought to identify interacting partners unique to cytoplasmic PELP1 and determine the mechanisms by which these interactions promote oncogenic PELP1 signaling. We identified AIB1 (amplified in breast cancer 1; also known as SRC-3 or NCOA3) as a novel binding partner of cytoplasmic PELP1 in both estrogen receptor-positive (ER+) and ER-negative cell lines. Cytoplasmic PELP1 expression elevated basal phosphorylation levels (i.e., activation) of AIB1, enhanced ALDH+ tumorsphere formation, and upregulated specific target genes independently of hormone stimulation. Direct manipulation of AIB1 levels using shRNA abrogated cytoplasmic PELP1-induced tumorsphere formation and downregulated cytoplasmic PELP1-specific target genes. SI-2, an AIB1 inhibitor, inhibited the PELP1/AIB1 interaction and decreased cytoplasmic PELP1-induced tumorsphere formation. Similar results were observed in a murine-derived MMTV-AIB1 tumor cell line (J110). Furthermore, in vivo syngeneic tumor studies showed that PELP1 knockdown in J110 cells resulted in increased survival of tumor-bearing mice as compared to mice injected with control cells. These studies suggest that manipulating PELP1 location or levels has the potential to mitigate tumor progression, particularly in the context of AIB1-mediated tumorigenesis. Taken together, our data demonstrate that cytoplasmic PELP1/AIB1-containing complexes function to promote advanced cancer phenotypes, including outgrowth of stem-like cells, associated with estrogen-independent breast cancer progression. Citation Format: Thu H. Truong, Hsiangyu Hu, Nuri A. Temiz, Kyla M. Hagen, Brian J. Girard, Nicholas J. Brady, Kathryn L. Schwertfeger, Carol A. Lange, Julie H. Ostrander. PELP1 and AIB1 (SRC-3) complexes promote cancer stem cell-associated phenotypes in ER+ breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 532.

Crossability among Five Cassava (Manihot Esculenta CRANTZ) Varieties

Controlled crosses were carried out to determine crossability among five selected cassava varieties in terms of seed set per cross and influence of maternal inheritance on seed set in cassava. The experiment was carried out at the Teaching and Research Farm of the Department of Agronomy, University of Ibadan Oyo State, Nigeria. Three yellow root varieties (IITA-TMS-I011412, IITA-TMS-I011368 and IITA-TMS-I070539) selected for their high β-carotene content and two white root varieties (IITA-TMS-I30752 and COB-7-25) selected for their high dry matter content and acceptable plant architecture among subsistence farmers were crossed in a reciprocal diallel design with no selfing. Fourteen hybrid populations were developed and data obtained were analyzed using T-Test and simple linear correlation. The result showed that genotype and maternal inheritance influenced seed setting in cassava. The cross IITA-TMS-I011368 x IITA-TMS-I011412 gave the highest seed set percentage (57.1) and the two parents were the best female and male parents, respectively. This was followed by IITA-TMS-I30752 x IITA-TMS-I011412 (39.8%), IITA-TMS-I011368 x IITA-TMS-I070539 (26.5%), IITA-TMS-I070539 x IITA-TMS-I011412 (24.9%) and IITA-TMS-I30752 x IITA-TMS-I011368 (24.1%). Reciprocal differences were observed for crosses between IITA-TMS-I30752 and IITA-TMS-I011412; IITA-TMS-I011412 and IITA-TMS-I011368; IITA-TMS-I011412 and COB-7-25 which suggests that seed setting in cassava is influenced by cytoplasmic genes which are transmitted exclusively by the maternal parent. The best female and male parents (IITA-TMS-I011368 and IITA-TMS-I011412) in terms of percentage seed set in this study are good candidates as parents to generate large populationsin breeding for high carotene content in cassava.

BAALC and ERG expression levels at diagnosis have no prognosis impact on acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT.

Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by PELP1/AIB1 Complexes.

Proline, glutamic acid, leucine-rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, interacting partners unique to cytoplasmic PELP1 and the mechanisms by which these interactions promote oncogenic PELP1 signaling were sought. AIB1 (amplified in breast cancer 1; also known as SRC-3 or NCOA3) was identified as a novel binding partner of cytoplasmic PELP1 in both estrogen receptor-positive (ER+) and ER-negative cell lines. Cytoplasmic PELP1 expression elevated basal phosphorylation levels (i.e., activation) of AIB1 at Thr24, enhanced ALDH+ tumorsphere formation, and upregulated specific target genes independently of hormone stimulation. Direct manipulation of AIB1 levels using shRNA abrogated cytoplasmic PELP1-induced tumorsphere formation and downregulated cytoplasmic PELP1-specific target genes. SI-2, an AIB1 inhibitor, limited the PELP1/AIB1 interaction and decreased cytoplasmic PELP1-induced tumorsphere formation. Similar results were observed in a murine-derived MMTV-AIB1 tumor cell line. Furthermore, in vivo syngeneic tumor studies revealed that PELP1 knockdown resulted in increased survival of tumor-bearing mice as compared with mice injected with control cells.Implications: These data demonstrate that cytoplasmic PELP1/AIB1-containing complexes function to promote advanced cancer phenotypes, including outgrowth of stem-like cells, associated with estrogen-independent breast cancer progression. Mol Cancer Res; 16(4); 707-19. ©2018 AACR.

Anacardic Acids from Cashew Nuts Prevent Behavioral Changes and Oxidative Stress Induced by Rotenone in a Rat Model of Parkinson’s Disease

Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100mg/kg/day) 1h before rotenone (3mg/kg; s.c.) for five consecutive days. The behavioral testing strategies, including tests for general locomotor activity (open field), motor coordination (rotarod), and spatial memory performance (elevated T-maze), were carried out. Lipoperoxidation levels and total superoxide dismutase (t-SOD) activity, as well as cytoplasmic and mitochondrial SOD gene expression, were assessed in the substantia nigra (SN), striatum, and cerebral cortex. The results showed that AAs dose-dependently prevented the rotenone-induced learning and motor impairment from 10mg/kg/day. AAs also precluded rotenone-induced lipoperoxidation in all doses, acting directly on the mitochondria, and improved the t-SOD activity in the doses 25-100mg/kg/day. AAs per se (100mg/kg/day) increased SOD gene expression and t-SOD activity. Our findings indicate that the oral administration of AAs prevents rotenone-induced behavioral changes and oxidative stress, in part due to a modulatory action on the mitochondria and SOD gene expression. These data suggest that AAs have promising neuroprotective action against degenerative changes in Parkinson's disease.

Unraveling the transcriptional complexity of compactness in sistan grape cluster

Yaghooti grape of Sistan is the earliest ripening grape in Iran, harvested every May annually. It is adapted to dry conditions in Sistan region and its water requirement is less than the other grape cultivars. The transcriptional complexity of this grape was studied in three stages of cluster development. Totally, 24121 genes were expressed in different cluster development steps (step 1: cluster formation, step 2: berry formation, step 3: final size of cluster) of which 3040 genes in the first stage, 2381 genes in the second stage and 2400 genes in the third stage showed a significant increase in expression. GO analysis showed that when the clusters are ripening, the activity of the nucleus, cytoplasmic, cytosol, membrane and chloroplast genes in the cluster architecture cells decreases. In contrast, the activity of the endoplasmic reticulum, vacuole and extracellular region genes enhances. When Yaghooti grape is growing and developing, some of metabolic pathways were activated in the response to biotic and abiotic stresses. Gene co-expression network reconstruction showed that AGAMOUS is a key gene in compactness of Sistan grape cluster, because it influences on expression of GA gene which leads to increase cluster length and berries size.