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Sample records for conserved testicular gene

  1. 3640 unique EST clusters from the medaka testis and their potential use for identifying conserved testicular gene expression in fish and mammals.

    PubMed

    Lo, Lijan; Zhang, Zhenhai; Hong, Ni; Peng, Jinrong; Hong, Yunhan

    2008-01-01

    The fish medaka is the first vertebrate capable of full spermatogenesis in vitro from self-renewing spermatogonial stem cells to motile test-tube sperm. Precise staging and molecular dissection of this process has been hampered by the lack of suitable molecular markers. We have generated a normalized medaka testis cDNA library and obtained 7040 high quality sequences representing 3641 unique gene clusters. Among these, 1197 unique clusters are homologous to known genes, and 2444 appear to be novel genes. Ontology analysis shows that the 1197 gene products are implicated in diverse molecular and cellular processes. These genes include markers for all major types of testicular somatic and germ cells. Furthermore, markers were identified for major spermatogenic stages ranging from spermatogonial stem cell self-renewal to meiosis entry, progression and completion. Intriguingly, the medaka testis expresses at least 13 homologs of the 33 mouse X-chromosomal genes that are enriched in the testis. More importantly, we show that key components of several signaling pathways known to be important for testicular function in mammals are well represented in the medaka testicular EST collection. Medaka exhibits a considerable similarity in testicular gene expression to mammals. The medaka testicular EST collection we obtained has wide range coverage and will not only consolidate our knowledge on the comparative analysis of known genes' functions in the testis but also provide a rich resource to dissect molecular events and mechanism of spermatogenesis in vivo and in vitro in medaka as an excellent vertebrate model.

  2. Gene conservation in California's forests

    Treesearch

    Constance I. Millar

    1986-01-01

    The University of California's Wildland Resources Center has established a new program of forest gene conservation to ensure that California's rich and diverse forests maintain their vigor and productivity in the face of human activities. At an international level, conservation biologists recognize the importance not only of protecting rare species from...

  3. Conservation and gene banking

    USDA-ARS?s Scientific Manuscript database

    Plant conservation has several objectives the main ones include safeguarding our food supply, preserving crop wild relatives for breeding and selection of new cultivars, providing material for industrial and pharmaceutical uses and preserving the beauty and diversity of our flora for generations to ...

  4. Targeted gene flow for conservation.

    PubMed

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens.

  5. Testicular gene expression of steroidogenesis-related factors in prepubertal, postpubertal, and aging dogs.

    PubMed

    Ogawa, E; Kawate, N; Inaba, T; Tamada, H

    2017-03-01

    Developmental and aging changes in testicular factors related to steroidogenesis are unknown in dogs. Using reverse transcription quantitative real-time PCR, this study examined testicular mRNA levels of CYP11A1 (P450 cholesterol side-chain cleavage enzyme, P450scc), CYP17A1 (P450 17α-hydroxylase/C17-20 lyase, P450c17), HSD3B2 (3β-hydroxysteroid dehydrogenase, 3β-HSD), CYP19A (P450 aromatase, P450arom), STAR (steroidogenic acute regulatory protein, StAR), cyclooxygenase (COX) -1 and COX-2 in prepubertal (4-6 months of age), postpubertal (1 year of age), and aging (2-18 years of age) dogs. Testicular mRNA levels for P450scc, 3β-HSD, StAR, COX-1, and COX-2 did not change from prepubertal to postpubertal stages, whereas that for P450arom markedly and abruptly increased and that for P450c17 gradually decreased. In postpubertal and aging dogs, a negative correlation was found between aging and testicular P450arom mRNA levels. Based on the rapid testicular growth observed during puberty, these results suggested that total testis gene expression for steroidogenesis-related factors, in particular for P450arom, increases during puberty in dogs. In addition, the decline in P450arom gene expression during aging may affect the ability to synthesize steroids in canine testes.

  6. AZF gene expression analysis in peripheral leukocytes and testicular cells from idiopathic infertility.

    PubMed

    Song, Ning-Hong; Yin, Chang-Jun; Zhang, Wei; Zhuo, Zuo-Min; Ding, Guan-Xiong; Zhang, Jing; Hua, Li-Xin; Wu, Hong-Fei

    2007-01-01

    The aim of this study was to assess the frequency of AZF microdeletions in peripheral leukocytes and testicular cells in Chinese men with idiopathic infertility. Expression in testicular cells was also determined. In this study, we screened 62 idiopathic infertile patients, in whom karyotype, sperm count and hormonal parameters were evaluated. Genomic DNA was extracted from the peripheral leukocytes. Molecular analysis was performed by two multiplex polymerase chain reactions (PCR) using a set of eight sequence tagged sites (STS) from 3 different regions of the Y chromosome. Total cellular RNA was extracted from the testicular tissue using a Trizol-method. Reverse Transcription (RT) reactions were performed to synthesize cDNA. Amplification of DFFRY, RBM and DAZ genes was performed to analyze their expression in testicular cells. In this cohort, we found 12 submicroscopic deletions (12/62, 19.4%). Nine patients (9/33, 27.2%) were detected in the azoospermic group and three (3/29, 10.3%) in the severe oligozoospermic group. RT-PCR analysis from testicular cells gave normal amplifications for SRY and DFFRY mRNA in 62 idiopathic patients; two patients were negative for RBM expression; no RBM and DAZ were detected for a case; 12 patients had no expression in the AZFc region involving the DAZ gene. Of 12 cases, three patients with normal PCR analysis of DAZ gene on genomic DNA showed no RT-PCR amplification for DAZ mRNA. The use of RT-PCR of specific spermatid expressed genes in conjunction with examining microdeletions using peripheral leukocytes is suggested to avoid the transmission of the Y chromosomal microdeletions from a father to a son via testicular sperm aspiration (TESE), intracytoplasmic sperm injection (JCSI).

  7. Evaluation of the decision-making process in the conservative approach to small testicular masses.

    PubMed

    Benelli, Andrea; Varca, Virginia; Derchi, Lorenzo; Gregori, Andrea; Carmignani, Giorgio; Simonato, Alchiede

    2017-04-28

    We evaluate the clinical outcome of patients treated with conservative approach for small testicular masses (STMs). We analyzed the steps who brought to the selection of the therapeutic approach: starting from clinical presentation, through imaging and lab studies. We considered 18 patients who underwent an organ-sparing approach for STMs from 2005 until 2014. The selection criteria were dimension of the mass and absence of clinical, laboratory and/or radiological malignancy suspicion. Preoperative scrotal ultrasound (US) was carried out in all the patients by the same radiologist. The postoperative fertility profile was evaluated in patients younger than 40 years. We performed 13 enucleations, one partial orchiectomy (PO) and four active surveillances. During surgery, a frozen section examination (FSE) was always requested and no discrepancies were noted between its results and the definitive histology. Only one seminomatous tumor was identified, while the remaining masses were four necrosis, four epidermoid cysts, three Leydig tumors, one Sertoli tumor and one chronic orchitis. After a mean follow-up of 41.6 ± 24.7 months, all the patients resulted free of disease and hypogonadism and five of them reached the fatherhood after surgery. The clinical and instrumental evaluation consented an accurate selection of patients eligible for the organ-preserving approach. We believe that testis-sparing surgery leads good functional and aesthetic results in patients with benign lesions; it is a safe option for STMs with a reliable pathologist performing FSE and is an important goal in young patients with fatherhood desire.

  8. Anchoring Ethinylestradiol Induced Gene Expression Changes with Testicular Morphology and Reproductive Function in the Medaka

    PubMed Central

    Miller, Hilary D.; Clark, Bryan W.; Hinton, David E.; Whitehead, Andrew; Martin, Stan; Kwok, Kevin W.; Kullman, Seth W.

    2012-01-01

    Environmental estrogens are ubiquitous in the environment and can cause detrimental effects on male reproduction. In fish, a multitude of effects from environmental estrogens have been observed including altered courting behavior and fertility, sex reversal, and gonadal histopathology. However, few studies in fish assess the impacts of estrogenic exposure on a physiological endpoint, such as reproduction, as well as the associated morphologic response and underlying global gene expression changes. This study assessed the implications of a 14 day sub-chronic exposure of ethinylestradiol (EE2; 1.0 or 10.0 µg/L EE2) on male medaka fertility, testicular histology and testicular gene expression. The findings demonstrate that a 14 day exposure to EE2 induced impaired male reproductive capacity and time- and dose-dependent alterations in testicular morphology and gene expression. The average fertilization rate/day following the exposure for control, 1.0 and 10.0 µg/L EE2 was 91.3% (±4.4), 62.8% (±8.3) and 28.8% (±5.8), respectively. The testicular morphologic alterations included increased germ cell apoptosis, decreased germinal epithelium and thickening of the interstitium. These changes were highly associated with testicular gene expression changes using a medaka-specific microarray. A pathway analysis of the differentially expressed genes emphasized genes and pathways associated with apoptosis, cell cycle and proliferation, collagen production/extracellular matrix organization, hormone signaling, male reproduction and protein ubiquitination among others. These findings highlight the importance of anchoring global gonadal gene expression changes with morphology and ultimately with tissue/organ function. PMID:23300682

  9. Phospholipid hydroperoxide glutathione peroxidase: expression pattern during testicular development in mouse and evolutionary conservation in spermatozoa.

    PubMed

    Nayernia, Karim; Diaconu, Mihaela; Aumüller, Gerhard; Wennemuth, Gunther; Schwandt, Iris; Kleene, Kenneth; Kuehn, Hartmut; Engel, Wolfgang

    2004-04-01

    Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a selenoprotein belonging to the family of glutathione peroxidases and has been implicated in antioxidative defense and spermatogenesis. PHGPx accounts for almost the entire selenium content of mammalian testis. In an attempt to verify the expression pattern of PHGPx, testes of mouse mutants with arrest at different stages of germ cell development and testes of mice at different ages were subjected to immunostaining with a monoclonal anti-PHGPx antibody. PHGPx was detected in Leydig cells of testes in all developmental stages. In the seminiferous tubuli, the PHGPx staining was first observed in testes of 21-day-old mice which is correlated with the appearance of the first spermatids. This result was confirmed when the testes of mutant mice with defined arrest of germ cell development were used. An immunostaining was observed in the seminiferous tubuli of olt/olt and qk/qk mice which show an arrest at spermatid differentiation. In Western blot analysis of proteins extracted from testes of mutant mice and from developing testes, two signals at 19- and 22-kDa were observed which confirm the existence of two PHGPx forms in testicular cells. In mouse spermatozoa, a subcellular localization of PHGPx and sperm mitochondria-associated cysteine-rich protein (SMCP) was demonstrated, indicating the localization of PHGPx in mitochondria of spermatozoa midpiece. For verifying the midpiece localization of PHGPx in other species, spermatozoa of Drosophila melanogaster, frog, fish, cock, mouse, rat, pig, bull, and human were used in immunostaining using anti-PHGPx antibody. A localization of PHGPx was found in the midpiece of spermatozoa in all species examined. In electronmicroscopical analysis, PHGPx signals were found in the mitochondria of midpiece. These results indicate a conserved crucial role of PHGPx during sperm function and male fertility.

  10. Expression of Neuropeptide Y gene in mouse testes during testicular development.

    PubMed

    Terado, M; Nomura, M; Mineta, K; Fujimoto, N; Matsumoto, T

    2006-07-01

    To elucidate the distribution and regulation of Neuropeptide Y (NPY) gene expression in testes under physiological and pathophysiological conditions, such as testicular development, fasting and experimental cryptorchidism. In the first experiment, C57BL/6J male mice at the ages of 3 days as well as 2, 3, 5 and 8 weeks were used. In the second and third experiments, adult C57BL/6J male mice were subjected to fasting for 48 h and experimental cryptorchidism for 72 h. The NPY transcripts were detected by isotopic in situ hybridization histochemistry. The NPY transcripts were exclusively expressed in the interstitial cells regardless of the age groups and experimental conditions. The NPY mRNA levels were found to increase significantly with age (from the neonatal to prepubertal period [P<0.01] and from the prepubetal to postpubertal period [P<0.01]). Food deprivation for 48 h resulted in a significant increase in the NPY mRNA levels in the arcuate nucleus of the hypothalamus (P<0.01), but not in the testes. Experimental cryptorchidism for 72 h failed to regulate the NPY gene expression in the testes. NPY gene expression is distributed in Leydig cells and increases in line with testicular development. The regulation of testicular NPY is different from that of hypothalamic NPY.

  11. Testicular cancer

    MedlinePlus

    Cancer - testes; Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer; Testicular neoplasm ... The exact cause of testicular cancer is unknown. Factors that may ... Abnormal testicle development Exposure to certain chemicals ...

  12. Forest gene conservation programs in Alberta, Canada

    Treesearch

    Jodie. Krakowski

    2017-01-01

    Provincial tree improvement programs in Alberta began in 1976. Early gene conservation focused on ex situ measures such as seed and clone banking, and research trials of commercial species with tree improvement programs. The gene conservation program now encompasses representative and unique populations of all native tree species in situ. The ex situ program aims to...

  13. Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial

    PubMed Central

    2011-01-01

    Background Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals. Results DHH, PTCH1 and PTCH2 were present in the marsupial genome and highly conserved with their eutherian orthologues. Phylogenetic analyses indicate that DHH has recently evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2 receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2 proteins. Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1. We also show that DHH expression was not restricted to the testes during gonadal development (as in mice), but was also expressed in the developing ovary. Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was consistent with findings in the adult mouse. Conclusions These data suggest that there is a highly conserved role for DHH signalling in the differentiation and function of the mammalian testis and that DHH may be necessary for marsupial ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads. Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis. PMID:22132805

  14. Testicular Exams

    MedlinePlus

    ... happens, surgery almost always repairs the hernia completely. Testicular Cancer Testicular cancer is unusual in teen guys, but it can happen. Testicular cancer is the most common cancer in guys aged ...

  15. Conservation strategies for forest gene resources

    Treesearch

    F. Thomas Ledig

    1986-01-01

    Gene conservation has three facets: (1) the maintenance of diversity in production plantations to buffer against vulnerability to pests and climatic extremes; (2) the preservation of genes for their future value in breeding; (3) the protection of species to promote ecosystem stability. Maintaining diversity as a hedge against damaging agents is a simple strategy in...

  16. DSCR9 gene simultaneous expression in placental, testicular and renal tissues from baboon (papio hamadryas)

    PubMed Central

    2012-01-01

    Background In 2002 Takamatsu and co-workers described the human DSCR9 gene and observed that it was transcriptionally active in human testicular tissue, but no protein was identified as a product of this transcript. Similar results were obtained in chimpanzee tissue. This gene has not been detected in species other than primates, suggesting that DSCR9 is exclusively found in these mammals. Results We report evidence of DSCR9 expression in placenta, testis and kidney of baboon (Papio hamadryas). We used primers specific for DSCR9 to amplify transcripts through reverse transcription (RT) coupled to polymerase chain reaction (PCR). Furthermore, PCR was used to amplify the complete DSCR9 gene from genomic DNA from three baboons. We amplified and sequenced five overlapping segments that were assembled into the 3284 bp baboon DSCR9 gene, including the putative promoter and the entire transcriptional unit (5'-UTR, CDS and 3'-UTR). Conclusions The baboon DSCR9 gene is highly similar to the human counterpart. The isolated transcripts from baboon tissues (placenta, testis and kidney) of three different baboons correspond to the human orthologous gene. PMID:22704171

  17. Highly Conserved Testicular Localization of Claudin-11 in Normal and Impaired Spermatogenesis

    PubMed Central

    Stammler, Angelika; Lüftner, Benjamin Udo; Kliesch, Sabine; Weidner, Wolfgang; Bergmann, Martin; Middendorff, Ralf; Konrad, Lutz

    2016-01-01

    In this study we tested expression of tight junction proteins in human, mouse and rat and analyzed the localization of claudin-11 in testis of patients with normal and impaired spermatogenesis. Recent concepts generated in mice suggest that the stage-specifically expressed claudin-3 acts as a basal barrier, sealing the seminiferous epithelium during migration of spermatocytes. Corresponding mechanisms have never been demonstrated in humans. Testicular biopsies (n = 103) from five distinct groups were analyzed: normal spermatogenesis (NSP, n = 28), hypospermatogenesis (Hyp, n = 24), maturation arrest at the level of primary spermatocytes (MA, n = 24), Sertoli cell only syndrome (SCO, n = 19), and spermatogonial arrest (SGA, n = 8). Protein expression of claudin-3, -11 and occludin was analyzed. Human, mice and rat testis robustly express claudin-11 protein. Occludin was detected in mouse and rat and claudin-3 was found only in mice. Thus, we selected claudin-11 for further analysis of localization. In NSP, claudin-11 is located at Sertoli-Sertoli junctions and in Sertoli cell contacts towards spermatogonia. Typically, claudin-11 patches do not reach the basal membrane, unless flanked by the Sertoli cell body or patches between two Sertoli cell bodies. The amount of basal claudin-11 patches was found to be increased in impaired spermatogenesis. Only claudin-11 is expressed in all three species examined. The claudin-11 pattern is robust in man with impaired spermatogenesis, but the proportion of localization is altered in SCO and MA. We conclude that claudin-11 might represent the essential component of the BTB in human. PMID:27486954

  18. Fold-change correction values for testicular somatic transcripts in gene expression studies of human spermatogenesis.

    PubMed

    Cappallo-Obermann, Heike; Feig, Caroline; Schulze, Wolfgang; Spiess, Andrej-Nikolai

    2013-03-01

    What are the reference values for delineating altered somatic cell gene expression from transcript enrichment/dilution in gene expression studies of human spermatogenesis? We have designed a crosstable and rule-of-thumb values for different stages of spermatogenic impairment that define the reference cut-off values for altered gene expression in Sertoli and Leydig cells in the context of impaired spermatogenesis. Morphometrical studies have shown that on the cellular level, impaired spermatogenesis results in a relative enrichment of somatic cell types. However, until now it is not known how this affects transcript levels in gene expression studies. In this study, 31 testis biopsies from men with different stages of spermatogenic impairment (full spermatogenesis, hypospermatogenesis, meiotic arrest, spermatogonial presence, Sertoli cell-only syndrome, complete tubular atrophy) were used to define reference ratios of somatic transcript enrichment/dilution. The reference ratios were validated on an independent test set of 28 samples and on gene expression data from men with Y-chromosomal microdeletions. High-quality microarray data were filtered with respect to Sertoli- and Leydig-cell-specific genes. General reference enrichment/dilution factors for these two cell types for all combinations of spermatogenic impairment were calculated using robust permutation statistics. To validate the specificity of the filtered transcripts, we calculated ratios for an independent test set of spermatogenic impairment and for transcriptional data from men with Y-chromosomal microdeletions, and checked the functional enrichment (gene ontology) and cellular localization of the corresponding proteins in a histological database and assessed their correlation with testicular size. Filtering of Sertoli- and Leydig-cell-specific genes resulted in a set of 54 and 332 transcripts, respectively. These were used in defining robust reference dilution/enrichment factors of somatic transcripts

  19. BRDT gene sequence in human testicular pathologies and the implication of its single nucleotide polymorphism (rs3088232) on fertility.

    PubMed

    Barda, S; Yogev, L; Paz, G; Yavetz, H; Lehavi, O; Hauser, R; Doniger, T; Breitbart, H; Kleiman, S E

    2014-07-01

    Bromodomain testis-specific (BRDT) protein is essential for the normal process of spermatogenesis. Mutant mice that expressed truncated BRDT had impaired testicular histology with severely reduced sperm concentration and abnormal sperm morphology, while a model of knockout Brdt mice with no BRDT protein had complete meiotic arrest. A BRDT single nucleotide polymorphism (SNP) (rs3088232) was reported as being associated with infertility in men. We assessed testicular specimens of 276 azoospermic men who underwent testicular sperm extraction to search for specimens that showed spermatogenic impairments similar to those of mutant BRDT mice. Ten similar specimens were selected for BRDT gene sequencing and they revealed three NCBI-reported SNPs (rs10783071, rs3088232 and rs10747493) variously distributed among them. Bioinformatics analysis predicted that they would not affect protein activity. Further assessment of rs3088232 frequency in a large group of non-obstructive azoospermia men and fertile controls demonstrated no significant difference between them (27.2 and 21.7% respectively; p = 0.122, Fisher's exact test). We conclude that the testicular impairments observed in the 10 specimens were not a consequence of BRDT gene mutation. The association between BRDT rs3088232 and infertility that had been reported in other studies was not supported.

  20. Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility.

    PubMed

    Litchfield, Kevin; Levy, Max; Dudakia, Darshna; Proszek, Paula; Shipley, Claire; Basten, Sander; Rapley, Elizabeth; Bishop, D Timothy; Reid, Alison; Huddart, Robert; Broderick, Peter; Castro, David Gonzalez de; O'Connor, Simon; Giles, Rachel H; Houlston, Richard S; Turnbull, Clare

    2016-12-20

    Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10(-8)). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported by a dnaaf1(hu255h)(+/-) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes.

  1. Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility

    PubMed Central

    Litchfield, Kevin; Levy, Max; Dudakia, Darshna; Proszek, Paula; Shipley, Claire; Basten, Sander; Rapley, Elizabeth; Bishop, D. Timothy; Reid, Alison; Huddart, Robert; Broderick, Peter; Castro, David Gonzalez de; O'Connor, Simon; Giles, Rachel H.; Houlston, Richard S.; Turnbull, Clare

    2016-01-01

    Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10−8). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported by a dnaaf1hu255h(+/−) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes. PMID:27996046

  2. Regulatory network of microRNAs and genes in testicular cancer

    PubMed Central

    Zhao, Yansong; Xu, Zhiwen; Wang, Ning; Wang, Shang

    2016-01-01

    Testicular cancer (TC) is the most common cancer in men between 20–40 years of age. A large number of studies have focused on identifying the cause of this disease; however, the underlying regulatory mechanisms have not been thoroughly investigated and the specific cause remains unclear. The present study systematically analyzed the regulatory associations between genes, transcription factors (TFs) and microRNAs (miRNAs), aiming to obtain key information regarding the regulatory processes of TC. Three different networks were derived from the analysis: Global, related and differentially-expressed. These networks may be able to identify the primary causes of TC through gene analysis, which determines underlying regulatory pathways and subsequently discloses information regarding TC pathology. The differentially-expressed network is considered to be the most important. If the differentially-expressed elements in this network were to be manipulated back to normal levels via human intervention, this may prevent the onset of TC. This may be described as suppressing TC at the genetic level. If the abnormal expression of these elements was to be corrected, then preventing TC at the source may be a feasible option. Thus, the present study compared and analyzed the global, related and differentially-expressed networks, from which important genetic pathways in TC were highlighted. In addition, self-adaptation associations, host genes and target genes were analyzed. The upstream and downstream elements were identified, and TFs were predicted using the P-match method. When combined, the results of the current study provide the basic materials for further research on important genes in TC, and provide guidance on the pathological curative method. PMID:27900048

  3. Testicular development involves the spatiotemporal control of PDGFs and PDGF receptors gene expression and action

    PubMed Central

    1995-01-01

    Platelet-derived growth factors (PDGFs) are growth-regulatory molecules that stimulate chemotaxis, proliferation and metabolism primarily of cells of mesenchymal origin. In this study, we found high levels of PDGFs and PDGFs receptors (PDGFRs) mRNAs, and specific immunostaining for the corresponding proteins in the rat testis. PDGFs and PDGFRs expression was shown to be developmentally regulated and tissue specific. Expression of PDGFs and PDGFRs genes was observed in whole testis RNA 2 d before birth, increased through postnatal day 5 and fell to low levels in adult. The predominant cell population expressing transcripts of the PDGFs and PDGFRs genes during prenatal and early postnatal periods were Sertoli cells and peritubular myoid cells (PMC) or their precursors, respectively, while in adult animals PDGFs and PDGFRs were confined in Leydig cells. We also found that early postnatal Sertoli cells produce PDGF-like substances and that this production is inhibited dose dependently by follicle-stimulating hormone (FSH). The expression of PDGFRs by PMC and of PDGFs by Sertoli cells corresponds in temporal sequence to the developmental period of PMC proliferation and migration from the interstitium to the peritubulum. Moreover, we observed that all the PDGF isoforms and the medium conditioned by early postnatal Sertoli cells show a strong chemotactic activity for PMC which is inhibited by anti-PDGF antibodies. These data indicate that, through the spatiotemporal pattern of PDGF ligands and receptors expression, PDGF may play a role in testicular development and homeostasis. PMID:7490286

  4. Evolutionarily conserved genes preferentially accumulate introns

    PubMed Central

    Carmel, Liran; Rogozin, Igor B.; Wolf, Yuri I.; Koonin, Eugene V.

    2007-01-01

    Introns that interrupt eukaryotic protein-coding sequences are generally thought to be nonfunctional. However, for reasons still poorly understood, positions of many introns are highly conserved in evolution. Previous reconstructions of intron gain and loss events during eukaryotic evolution used a variety of simplified evolutionary models that yielded contradicting conclusions and are not suited to reveal some of the key underlying processes. We combine a comprehensive probabilistic model and an extended data set, including 391 conserved genes from 19 eukaryotes, to uncover previously unnoticed aspects of intron evolution—in particular, to assign intron gain and loss rates to individual genes. The rates of intron gain and loss in a gene show moderate positive correlation. A gene’s intron gain rate shows a highly significant negative correlation with the coding-sequence evolution rate; intron loss rate also significantly, but positively, correlates with the sequence evolution rate. Correlations of the opposite signs, albeit less significant ones, are observed between intron gain and loss rates and gene expression level. It is proposed that intron evolution includes a neutral component, which is manifest in the positive correlation between the gain and loss rates and a selection-driven component as reflected in the links between intron gain and loss and sequence evolution. The increased intron gain and decreased intron loss in evolutionarily conserved genes indicate that intron insertion often might be adaptive, whereas some of the intron losses might be deleterious. This apparent functional importance of introns is likely to be due, at least in part, to their multiple effects on gene expression. PMID:17495009

  5. Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) enhances testicular gene expression of 3β-hydroxysteroid dehydrogenase in rats.

    PubMed

    Ohta, Y; Kawate, N; Inaba, T; Morii, H; Takahashi, K; Tamada, H

    2017-03-06

    Although feeding diets containing the extract powder of Lepidium meyenii (maca), a plant growing in Peru's Central Andes, increases serum testosterone concentration associated with enhanced ability of testosterone production by Leydig cells in male rats, changes in testicular steroidogenesis-related factors by the maca treatment are not known. This study examined the effects of maca on testicular gene expressions for luteinizing hormone receptor, steroidogenic acute regulatory protein and steroidogenic enzymes. Eight-week-old male rats were given the diets with or without (control) the maca extract powder (2%) for 6 weeks, and mRNA levels were determined by reverse transcription quantitative real-time PCR. The results showed that the testicular mRNA level of HSD3B1 (3β-hydroxysteroid dehydrogenase; 3β-HSD) increased by the treatment, whereas the levels of the other factors examined did not change. These results suggest that increased expression of 3β-HSD gene may be involved in the enhanced steroidogenic ability by the maca treatment in rat testes.

  6. Conservation of gene function in behaviour

    PubMed Central

    Reaume, Christopher J.; Sokolowski, Marla B.

    2011-01-01

    Behaviour genetic research has shown that a given gene or gene pathway can influence categorically similar behaviours in different species. Questions about the conservation of gene function in behaviour are increasingly tractable. This is owing to the surge of DNA and 'omics data, bioinformatic tools, as well as advances in technologies for behavioural phenotyping. Here, we discuss how gene function, as a hierarchical biological phenomenon, can be used to examine behavioural homology across species. The question can be addressed independently using different levels of investigation including the DNA sequence, the gene's position in a genetic pathway, spatial–temporal tissue expression and neural circuitry. Selected examples from the literature are used to illustrate this point. We will also discuss how qualitative and quantitative comparisons of the behavioural phenotype, its function and the importance of environmental and social context should be used in cross-species comparisons. We conclude that (i) there are homologous behaviours, (ii) they are hard to define and (iii) neurogenetics and genomics investigations should help in this endeavour. PMID:21690128

  7. Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression.

    PubMed

    Eleawa, Samy M; Alkhateeb, Mahmoud A; Alhashem, Fahaid H; Bin-Jaliah, Ismaeel; Sakr, Hussein F; Elrefaey, Hesham M; Elkarib, Abbas O; Alessa, Riyad M; Haidara, Mohammad A; Shatoor, Abdullah S; Khalil, Mohammad A

    2014-04-24

    This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

  8. Regulation network analysis of testicular seminoma at various stages of progression.

    PubMed

    Sha, J-J; Dong, Y-H; Liu, D-M; Bo, J-J; Huang, Y-R; Li, Z; Ping, P

    2013-03-11

    Testicular seminoma has become the most common solid malignancy in young men, especially in the 20s group. We obtained the gene expression profile of human testicular seminoma cells from NCBI, identified the differentially expressed genes of testicular seminoma cells of different stages, and constructed the regulation networks of different stages of testicular seminoma using bioinformatics methodology. Forty differentially expressed genes of testicular seminoma cells of different stages were identified. These genes and pathways are apparently involved in the progression of testicular seminoma.

  9. Gene context conservation of a higher order than operons.

    PubMed

    Lathe, W C; Snel, B; Bork, P

    2000-10-01

    Operons, co-transcribed and co-regulated contiguous sets of genes, are poorly conserved over short periods of evolutionary time. The gene order, gene content and regulatory mechanisms of operons can be very different, even in closely related species. Here, we present several lines of evidence which suggest that, although an operon and its individual genes and regulatory structures are rearranged when comparing the genomes of different species, this rearrangement is a conservative process. Genomic rearrangements invariably maintain individual genes in very specific functional and regulatory contexts. We call this conserved context an uber-operon.

  10. Gene conservation of tree species—banking on the future

    Treesearch

    Richard A. Sniezko; Gary Man; Valerie Hipkins; Keith Woeste; David Gwaze; John T. Kliejunas; Brianna A. McTeague

    2017-01-01

    The ‘Gene Conservation of Tree Species—Banking on the Future Workshop’ provided a forum for presenting and discussing issues and accomplishments in genetic conservation of trees, and notably those of North America. The meeting gathered scientists, specialists, administrators and conservation practitioners from federal, university, non-governmental and public garden...

  11. Testicular failure

    MedlinePlus

    ... Blood tests may show a low level of testosterone and high levels of prolactin, FSH , and LH . ... testes will be ordered. Testicular failure and low testosterone level may be hard to diagnose in older ...

  12. Testicular Injuries

    MedlinePlus

    ... Also, the location of the testicles makes them prime targets to be accidentally struck on the playing ... you might also feel nauseated for a short time. If it's a minor testicular injury, the pain ...

  13. Testicular Torsion

    MedlinePlus

    ... Journal of Urology. 2011;185:2469. Hittelman AB. Neonatal testicular torsion. http://www.uptodate.com/home. Accessed ... 16, 2015. Snyder HM, et al. In utero/neonatal torsion: Observation versus prompt exploration. Journal of Urology. ...

  14. Testicular self-exam

    MedlinePlus

    Screening - testicular cancer - self-exam; Testicular cancer - screening - self-exam ... A testicular self-exam is done to check for testicular cancer . Testicles have blood vessels and other structures that can make ...

  15. Molecular identification of genes involved in testicular steroid synthesis and characterization of the responses to hormones stimulation in testis of Japanese sea bass (Lateolabrax japonicas).

    PubMed

    Chi, Mei L; Wen, Hai S; Ni, Meng; He, Feng; Li, Ji F; Qian, Kun; Zhang, Pei; Chai, Sen H; Ding, Yu X; Yin, Xiang H

    2014-06-01

    Testicular steroids are critical hormones for the regulation of spermatogenesis in male teleosts and their productions have been reported to be regulated by gonadotropins and gonadotropin-releasing hormone. In the Japanese sea bass (Lateolabrax japonicas), the reproductive endocrine, particularly regarding the production and regulation of testicular steroids, are not well understood. For this reason, we first cloned and characterized the response of several key genes regulating the production of testicular steroids and, second, we analyzed the changes of mRNA profiles of these genes during testicular development cycle and in the administration of hCG and GnRHa with corresponding testosterone level in serum, GSI and histological analyses. We succeeded in cloning the full-length cDNAs for the fushi tarazu factor-1 (FTZ-F1) homologues (FTZ-F1a and FTZ-F1b), steroidogenic acute regulatory protein (StAR) and anti-Müllerian hormone (AMH) in Japanese sea bass. Multiple sequence alignment and phylogenetic analysis of these proteins clearly showed that these genes in Japanese sea bass were homologous to those of other piscine species. During the testicular development cycle and hCG/GnRHa administration, quantification of jsbStAR transcripts revealed a trend similar to their serum testosterone levels, while a reciprocal relationship was founded between the serum concentrations of testosterone and jsbAMH and the links between gonadal expression of jsbStAR, jsbAMH and jsbFTZ-F1 were also observed. Our results have identified for the first time several key genes involved in the regulation of steroid production and spermatogenesis in the Japanese sea bass testis and these genes are all detected under gonadotropic hormone and gonadotropin-releasing hormone control.

  16. Testicular torsion.

    PubMed

    Ringdahl, Erika; Teague, Lynn

    2006-11-15

    Each year, testicular torsion affects one in 4,000 males younger than 25 years. Early diagnosis and definitive management are the keys to avoid testicular loss. All prepubertal and young adult males with acute scrotal pain should be considered to have testicular torsion until proven otherwise. The finding of an ipsilateral absent cremasteric reflex is the most accurate sign of testicular torsion. Torsion of the appendix testis is more common in children than testicular torsion and may be diagnosed by the "blue dot sign" (i.e., tender nodule with blue discoloration on the upper pole of the testis). Epididymitis/orchitis is much less common in the prepubertal male, and the diagnosis should be made with caution in this age group. Doppler ultrasonography may be needed for definitive diagnosis; radionuclide scintigraphy is an alternative that may be more accurate but should be ordered only if it can be performed without delay. Diagnosis of testicular torsion is based on the finding of decreased or absent blood flow on the ipsilateral side. Treatment involves rapid restoration of blood flow to the affected testis. The optimal time frame is less than six hours after the onset of symptoms. Manual detorsion by external rotation of the testis can be successful, but restoration of blood flow must be confirmed following the maneuver. Surgical exploration provides definitive treatment for the affected testis by orchiopexy and allows for prophylactic orchiopexy of the contralateral testis. Surgical treatment of torsion of the appendix testis is not mandatory but hastens recovery.

  17. Conservation of alternative polyadenylation patterns in mammalian genes.

    PubMed

    Ara, Takeshi; Lopez, Fabrice; Ritchie, William; Benech, Philippe; Gautheret, Daniel

    2006-07-26

    Alternative polyadenylation is a widespread mechanism contributing to transcript diversity in eukaryotes. Over half of mammalian genes are alternatively polyadenylated. Our understanding of poly(A) site evolution is limited by the lack of a reliable identification of conserved, equivalent poly(A) sites among species. We introduce here a working definition of conserved poly(A) sites as sites that are both (i) properly aligned in human and mouse orthologous 3' untranslated regions (UTRs) and (ii) supported by EST or cDNA data in both species. We identified about 4800 such conserved poly(A) sites covering one third of the orthologous gene set studied. Characteristics of conserved poly(A) sites such as processing efficiency and tissue-specificity were analyzed. Conserved sites show a higher processing efficiency but no difference in tissular distribution when compared to non-conserved sites. In general, alternative poly(A) sites are species-specific and involve minor, non-conserved sites that are unlikely to play essential roles. However, there are about 500 genes with conserved tandem poly(A) sites. A significant fraction of these conserved tandems display a conserved arrangement of major/minor sites in their 3' UTR, suggesting that these alternative 3' ends may be under selection. This analysis allows us to identify potential functional alternative poly(A) sites and provides clues on the selective mechanisms at play in the appearance of multiple poly(A) sites and their maintenance in the 3' UTRs of genes.

  18. Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the human genome sequence

    PubMed Central

    Osada, Naoki; Hida, Munetomo; Kusuda, Jun; Tanuma, Reiko; Hirata, Makoto; Suto, Yumiko; Hirai, Momoki; Terao, Keiji; Sugano, Sumio; Hashimoto, Katsuyuki

    2002-01-01

    Background In order to contribute to the establishment of a complete map of transcribed regions of the human genome, we constructed a testicular cDNA library for the cynomolgus monkey, and attempted to find novel transcripts for identification of their human homologues. Result The full-insert sequences of 512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs carrying open reading frames of 300 bp-length or longer. Among them, 89 cDNAs were found not to be annotated previously in the Ensembl human database. After searching against the Ensembl mouse database, we also found 69 putative coding sequences have no homologous cDNAs in the annotated human and mouse genome sequences in Ensembl. We subsequently designed a DNA microarray including 396 non-redundant cDNAs (with and without open reading frames) to examine the expression of the full-sequenced genes. With the testicular probe and a mixture of probes of 10 other tissues, 316 of 332 effective spots showed intense hybridized signals and 75 cDNAs were shown to be expressed very highly in the cynomolgus monkey testis, but not ubiquitously. Conclusions In this report, we determined 302 full-insert sequences of cynomolgus monkey cDNAs with enough length of open reading frames to discover novel transcripts as human homologues. Among 302 cDNA sequences, human homologues of 89 cDNAs have not been predicted in the annotated human genome sequence in the Ensembl. Additionally, we identified 75 dominantly expressed genes in testis among the full-sequenced clones by using a DNA microarray. Our cDNA clones and analytical results will be valuable resources for future functional genomic studies. PMID:12498619

  19. How developments in cryobiology, reproductive technologies and conservation genomics could shape gene banking strategies for (farm) animals.

    PubMed

    Woelders, H; Windig, J; Hiemstra, S J

    2012-08-01

    Many local breeds are currently at risk because of replacement by a limited number of specialized commercial breeds. Concurrently, for many breeds, allelic diversity within breeds declines because of inbreeding. Gene banking of germplasm may serve to secure the breeds and the alleles for any future use, for instance to recover a lost breed, to address new breeding goals, to support breeding schemes in small populations to minimize inbreeding, and for conservation genetics and genomics research. Developments in cryobiology and reproductive technology have generated several possibilities for preserving germplasm in farm animals. Furthermore, in some mammalian and bird species, gene banking of material is difficult or impossible, requiring development of new alternative methods or improvement of existing methods. Depending on the species, there are interesting possibilities or research developments in the use of epididymal spermatozoa, oocytes and embryos, ovarian and testicular tissue, primordial germ cells, and somatic cells for the conservation of genetic diversity in farm- and other animal species. Rapid developments in genomics research also provide new opportunities to optimize conservation and sampling strategies and to characterize genome-wide genetic variation. With regard to gene banks for farm animals, collaboration between European countries is being developed through a number of organizations, aimed at sharing knowledge and expertise between national programmes. It would be useful to explore further collaboration between countries, within the framework of a European gene banking strategy that should minimize costs of conservation and maximize opportunities for exploitation and sustainable use of genetic diversity.

  20. Radiation Therapy for Testicular Cancer

    MedlinePlus

    ... Treating Testicular Cancer Surgery for Testicular Cancer Radiation Therapy for Testicular Cancer Chemotherapy for Testicular Cancer High-Dose Chemotherapy and ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  1. A Study of Differential Expression of Testicular Genes in Various Reproductive Phases of Hemidactylus flaviviridis (Wall Lizard) to Derive Their Association with Onset of Spermatogenesis and Its Relevance to Mammals.

    PubMed

    Sarkar, Hironmoy; Arya, Satyapal; Rai, Umesh; Majumdar, Subeer S

    2016-01-01

    Testis of Hemidactylus flaviviridis, commonly known as Indian wall lizard, displays a lack of cellular and metabolic activity in regressed phase of testis during non-breeding season of the year. Retracted Sertoli cells (Sc), fibroid myoid cells and pre-meiotic resting spermatogonia are observed in such testis. This situation is akin to certain forms of infertility in men where hormone supplementation fails to generate sperm despite the presence of Sc and germ cells (Gc) in testis. In testis of lizard, spermatogenesis is reinitiated upon increased level of hormones during appropriate season (phase of recrudescence). Study of genes associated with generation of sperm, from regressed adult testis in lizard, may provide valuable information for understanding certain forms of male idiopathic infertility. Subtractive hybridization using testicular RNA obtained from the regressed and active phases of lizard reproductive cycle led to identify eight partial mRNA sequences that showed sequence homology with mice genes. We further evaluated the gene expression prolife by real-time PCR in three different reproductive phases of H. flaviviridis: regressed (pre-meiotic), recrudescent (meiotic) and active (post meiotic), for comparison with the corresponding testicular phases found in testis of 5 days (pre-meiotic), 20 days (meiotic) and 60 days (post-meiotic) old mouse. This is the first report where genes associated with progression of spermatogenesis during active phase, which follows a regressed state of adult testis, were identified in lizard and found to be conserved in mouse. Six important genes, Hk1, Nme5, Akap4, Arih1, Rassf7 and Tubb4b were found to be strictly associated with active spermatogenesis in both mouse and lizard. Factors interfering with the expression of any of these genes may potentially abrogate the process of spermatogenesis leading to infertility. Such information may shed light on unknown causes of idiopathic male infertility.

  2. A Study of Differential Expression of Testicular Genes in Various Reproductive Phases of Hemidactylus flaviviridis (Wall Lizard) to Derive Their Association with Onset of Spermatogenesis and Its Relevance to Mammals

    PubMed Central

    Sarkar, Hironmoy; Arya, Satyapal; Rai, Umesh; Majumdar, Subeer S.

    2016-01-01

    Testis of Hemidactylus flaviviridis, commonly known as Indian wall lizard, displays a lack of cellular and metabolic activity in regressed phase of testis during non-breeding season of the year. Retracted Sertoli cells (Sc), fibroid myoid cells and pre-meiotic resting spermatogonia are observed in such testis. This situation is akin to certain forms of infertility in men where hormone supplementation fails to generate sperm despite the presence of Sc and germ cells (Gc) in testis. In testis of lizard, spermatogenesis is reinitiated upon increased level of hormones during appropriate season (phase of recrudescence). Study of genes associated with generation of sperm, from regressed adult testis in lizard, may provide valuable information for understanding certain forms of male idiopathic infertility. Subtractive hybridization using testicular RNA obtained from the regressed and active phases of lizard reproductive cycle led to identify eight partial mRNA sequences that showed sequence homology with mice genes. We further evaluated the gene expression prolife by real-time PCR in three different reproductive phases of H. flaviviridis: regressed (pre-meiotic), recrudescent (meiotic) and active (post meiotic), for comparison with the corresponding testicular phases found in testis of 5 days (pre-meiotic), 20 days (meiotic) and 60 days (post-meiotic) old mouse. This is the first report where genes associated with progression of spermatogenesis during active phase, which follows a regressed state of adult testis, were identified in lizard and found to be conserved in mouse. Six important genes, Hk1, Nme5, Akap4, Arih1, Rassf7 and Tubb4b were found to be strictly associated with active spermatogenesis in both mouse and lizard. Factors interfering with the expression of any of these genes may potentially abrogate the process of spermatogenesis leading to infertility. Such information may shed light on unknown causes of idiopathic male infertility. PMID:26963275

  3. Polymorphism of the CTNNB1 and FOXL2 Genes is not Associated with Canine XX Testicular/Ovotesticular Disorder of Sex Development.

    PubMed

    Salamon, Sylwia; Nowacka-Woszuk, Joanna; Switonski, Marek

    2015-01-01

    78,XX testicular or ovotesticular disorder of sex development (DSD) is the most common sex anomaly in dogs, but its molecular background remains unknown. It was hypothesized that the causative mutation may reside in canine chromosome 23 (CFA23), where two genes playing a pivotal role in ovarian development (CTNNB1 and FOXL2) are located. The aim of our study was to search for polymorphism in both candidate genes in 15 DSD dogs (78,XX and a lack of the SRYgene) and 29 normal females. Altogether, 7 novel polymorphic variants were identified: 5 SNPs in CTNNB1 and 2 indels in the FOXL2 gene. The distribution of the identified variants was similar in the DSD and control dogs. Therefore, we concluded that the conducted research did not prove an association between these polymorphisms and canine testicular or ovotesticular XX DSD.

  4. Isoform-Level Gene Expression Profiles of Human Y Chromosome Azoospermia Factor Genes and Their X Chromosome Paralogs in the Testicular Tissue of Non-Obstructive Azoospermia Patients.

    PubMed

    Ahmadi Rastegar, Diba; Sharifi Tabar, Mehdi; Alikhani, Mehdi; Parsamatin, Pouria; Sahraneshin Samani, Fazel; Sabbaghian, Marjan; Sadighi Gilani, Mohammad Ali; Mohammad Ahadi, Ali; Mohseni Meybodi, Anahita; Piryaei, Abbas; Ansari-Pour, Naser; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2015-09-04

    The human Y chromosome has an inevitable role in male fertility because it contains many genes critical for spermatogenesis and the development of the male gonads. Any genetic variation or epigenetic modification affecting the expression pattern of Y chromosome genes may thus lead to male infertility. In this study, we performed isoform-level gene expression profiling of Y chromosome genes within the azoospermia factor (AZF) regions, their X chromosome counterparts, and few autosomal paralogues in testicular biopsies of 12 men with preserved spermatogenesis and 68 men with nonobstructive azoospermia (NOA) (40 Sertoli-cell-only syndrome (SCOS) and 28 premiotic maturation arrest (MA)). This was undertaken using quantitative real-time PCR (qPCR) at the transcript level and Western blotting (WB) and immunohistochemistry (IHC) at the protein level. We profiled the expression of 41 alternative transcripts encoded by 14 AZFa, AZFb, and AZFc region genes (USP9Y, DDX3Y, XKRY, HSFY1, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2, RBMY1A1, PRY, BPY2, DAZ1, and CDY1) as well as their X chromosome homologue transcripts and a few autosomal homologues. Of the 41 transcripts, 18 were significantly down-regulated in men with NOA when compared with those of men with complete spermatogenesis. In contrast, the expression of five transcripts increased significantly in NOA patients. Furthermore, to confirm the qPCR results at the protein level, we performed immunoblotting and IHC experiments (based on 24 commercial and homemade antibodies) that detected 10 AZF-encoded proteins. In addition, their localization in testis cell types and organelles was determined. Interestingly, the two missing proteins, XKRY and CYORF15A, were detected for the first time. Finally, we focused on the expression patterns of the significantly altered genes in 12 MA patients with successful sperm retrieval compared to those of 12 MA patients with failed sperm retrieval to predict the success of sperm retrieval in

  5. Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

    PubMed

    Koster, Roelof; Mitra, Nandita; D'Andrea, Kurt; Vardhanabhuti, Saran; Chung, Charles C; Wang, Zhaoming; Loren Erickson, R; Vaughn, David J; Litchfield, Kevin; Rahman, Nazneen; Greene, Mark H; McGlynn, Katherine A; Turnbull, Clare; Chanock, Stephen J; Nathanson, Katherine L; Kanetsky, Peter A

    2014-11-15

    Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT.

  6. Testicular Adrenal Rest Tumor in Two Brothers with a Novel Mutation in the 3-Beta-Hydroxysteroid Dehydrogenase-2 Gene

    PubMed Central

    Güven, Ayla; Polat, Seher

    2017-01-01

    Testicular adrenal rest tumors (TART) occur frequently in adolescents and adults with 21-hydroxylase deficiency. There have been no reports of TART in children with 3β-hydroxysteroid dehydrogenase deficiency (HSD3β). Biopsy proven TART was diagnosed in a 31/12-year-old male patient and also in his 22-month-old sibling. Hormonal and anthropometric measurements were performed during glucocorticoid and fludrocortisone treatment. The mutational analysis was performed by direct DNA sequencing of the complete coding region of the HSD3β2 gene. Initially, both siblings were treated with high doses of hydrocortisone and fludrocortisone. TART regressed with dexamethasone treatment in both patients. However, growth velocity decreased and weight gain increased in both patients. Dexamethasone was changed to high-dose hydrocortisone (>20 mg/m2/d). Sequencing analyses revealed a novel homozygous p.W355R (c.763 T>C) mutation at exon 4 of the HSD3β2 gene in both siblings. These two patients are, to our knowledge, the first known cases of TARTs with a novel mutation in the HSD3β2 gene detected during childhood. High-dose hydrocortisone treatment is more reliable for TART in children. PMID:27476613

  7. A sexual shift induced by silencing of a single insulin-like gene in crayfish: ovarian upregulation and testicular degeneration.

    PubMed

    Rosen, Ohad; Manor, Rivka; Weil, Simy; Gafni, Ohad; Linial, Assaf; Aflalo, Eliahu D; Ventura, Tomer; Sagi, Amir

    2010-12-09

    In sequential hermaphrodites, intersexuality occurs naturally, usually as a transition state during sexual re-differentiation processes. In crustaceans, male sexual differentiation is controlled by the male-specific androgenic gland (AG). An AG-specific insulin-like gene, previously identified in the red-claw crayfish Cherax quadricarinatus (designated Cq-IAG), was found in this study to be the prominent transcript in an AG cDNA subtractive library. In C. quadricarinatus, sexual plasticity is exhibited by intersex individuals in the form of an active male reproductive system and male secondary sex characters, along with a constantly arrested ovary. This intersexuality was exploited to follow changes caused by single gene silencing, accomplished via dsRNA injection. Cq-IAG silencing induced dramatic sex-related alterations, including male feature feminization, a reduction in sperm production, extensive testicular degeneration, expression of the vitellogenin gene, and accumulation of yolk proteins in the developing oocytes. Upon silencing of the gene, AG cells hypertrophied, possibly to compensate for low hormone levels, as reflected in the poor production of the insulin-like hormone (and revealed by immunohistochemistry). These results demonstrate both the functionality of Cq-IAG as an androgenic hormone-encoding gene and the dependence of male gonad viability on the Cq-IAG product. This study is the first to provide evidence that silencing an insulin-like gene in intersex C. quadricarinatus feminizes male-related phenotypes. These findings, moreover, contribute to the understanding of the regulation of sexual shifts, whether naturally occurring in sequential hermaphrodites or abnormally induced by endocrine disruptors found in the environment, and offer insight into an unusual gender-related link to the evolution of insulins.

  8. Conserved gene structures and expression signals in methanogenic archaebacteria.

    PubMed

    Allmansberger, R; Bokranz, M; Kröckel, L; Schallenberg, J; Klein, A

    1989-01-01

    A comparative analysis of cotranscribed gene clusters comprising the structural genes mcrA, mcrB, mcrC, mcrD, and mcrG was carried out in three species of methanogens. mcrA, mcrB, and mcrG are the structural genes for the three subunits of methyl coenzyme M reductase, while the two other genes encode polypeptides of unknown functions. The degree of conservation of the mcr gene products among different species of methanogens varies. No correlation was found between the conservation of the G+C contents of the homologous genes and of the amino acid sequences of their products among the different bacteria. The comparison of RNA polymerase core subunit genes of Methanobacterium thermoautotrophicum as evolutionary markers with their equivalents in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster showed that homologous polypeptide domains are encoded by different numbers of genes suggesting gene fusion of adjacent genes in the course of evolution. The archaebacterial subunits exhibit much stronger homology with their eukaryotic than with their eubacterial equivalents on the polypeptide sequence level. All the analyzed genes are preceded by ribosome binding sites of eubacterial type. In addition to known putative promoter sequences, conserved structural elements of the DNA were detected surrounding the transcription initiation sites of the mcr genes.

  9. Conservation of alternative polyadenylation patterns in mammalian genes

    PubMed Central

    Ara, Takeshi; Lopez, Fabrice; Ritchie, William; Benech, Philippe; Gautheret, Daniel

    2006-01-01

    Background Alternative polyadenylation is a widespread mechanism contributing to transcript diversity in eukaryotes. Over half of mammalian genes are alternatively polyadenylated. Our understanding of poly(A) site evolution is limited by the lack of a reliable identification of conserved, equivalent poly(A) sites among species. We introduce here a working definition of conserved poly(A) sites as sites that are both (i) properly aligned in human and mouse orthologous 3' untranslated regions (UTRs) and (ii) supported by EST or cDNA data in both species. Results We identified about 4800 such conserved poly(A) sites covering one third of the orthologous gene set studied. Characteristics of conserved poly(A) sites such as processing efficiency and tissue-specificity were analyzed. Conserved sites show a higher processing efficiency but no difference in tissular distribution when compared to non-conserved sites. In general, alternative poly(A) sites are species-specific and involve minor, non-conserved sites that are unlikely to play essential roles. However, there are about 500 genes with conserved tandem poly(A) sites. A significant fraction of these conserved tandems display a conserved arrangement of major/minor sites in their 3' UTR, suggesting that these alternative 3' ends may be under selection. Conclusion This analysis allows us to identify potential functional alternative poly(A) sites and provides clues on the selective mechanisms at play in the appearance of multiple poly(A) sites and their maintenance in the 3' UTRs of genes. PMID:16872498

  10. Evolutionary conservation of regulatory elements in vertebrate HOX gene clusters

    SciTech Connect

    Santini, Simona; Boore, Jeffrey L.; Meyer, Axel

    2003-12-31

    Due to their high degree of conservation, comparisons of DNA sequences among evolutionarily distantly-related genomes permit to identify functional regions in noncoding DNA. Hox genes are optimal candidate sequences for comparative genome analyses, because they are extremely conserved in vertebrates and occur in clusters. We aligned (Pipmaker) the nucleotide sequences of HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human and mouse (over 500 million years of evolutionary distance). We identified several highly conserved intergenic sequences, likely to be important in gene regulation. Only a few of these putative regulatory elements have been previously described as being involved in the regulation of Hox genes, while several others are new elements that might have regulatory functions. The majority of these newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac). The conserved intergenic regions located between the most rostrally expressed genes in the developing embryo are longer and better retained through evolution. We document that presumed regulatory sequences are retained differentially in either A or A clusters resulting from a genome duplication in the fish lineage. This observation supports both the hypothesis that the conserved elements are involved in gene regulation and the Duplication-Deletion-Complementation model.

  11. Testicular Disorders

    MedlinePlus

    ... boys should wear athletic supporters when they play sports. You should examine your testicles monthly and seek medical attention for lumps, redness, pain or other changes. Testicles can get inflamed or infected. They can also develop cancer. Testicular cancer is rare and highly treatable. It ...

  12. Testicular Cancer

    MedlinePlus

    ... of skin behind the penis. You can get cancer in one or both testicles. Testicular cancer mainly affects young men between the ages of ... undescended testicle Have a family history of the cancer Symptoms include pain, swelling, or lumps in your ...

  13. Inferring Functional Relationships from Conservation of Gene Order.

    PubMed

    Moreno-Hagelsieb, Gabriel

    2017-01-01

    Predicting functional associations using the Gene Neighbor Method depends on the simple idea that if genes are conserved next to each other in evolutionarily distant prokaryotes they might belong to a polycistronic transcription unit. The procedure presented in this chapter starts with the organization of the genes within genomes into pairs of adjacent genes. Then, the pairs of adjacent genes in a genome of interest are mapped to their corresponding orthologs in other, informative, genomes. The final step is to verify if the mapped orthologs are also pairs of adjacent genes in the informative genomes.

  14. Patterns of conservation and change in honey bee developmental genes.

    PubMed

    Dearden, Peter K; Wilson, Megan J; Sablan, Lisha; Osborne, Peter W; Havler, Melanie; McNaughton, Euan; Kimura, Kiyoshi; Milshina, Natalia V; Hasselmann, Martin; Gempe, Tanja; Schioett, Morten; Brown, Susan J; Elsik, Christine G; Holland, Peter W H; Kadowaki, Tatsuhiko; Beye, Martin

    2006-11-01

    The current insect genome sequencing projects provide an opportunity to extend studies of the evolution of developmental genes and pathways in insects. In this paper we examine the conservation and divergence of genes and developmental processes between Drosophila and the honey bee; two holometabolous insects whose lineages separated approximately 300 million years ago, by comparing the presence or absence of 308 Drosophila developmental genes in the honey bee. Through examination of the presence or absence of genes involved in conserved pathways (cell signaling, axis formation, segmentation and homeobox transcription factors), we find that the vast majority of genes are conserved. Some genes involved in these processes are, however, missing in the honey bee. We have also examined the orthology of Drosophila genes involved in processes that differ between the honey bee and Drosophila. Many of these genes are preserved in the honey bee despite the process in which they act in Drosophila being different or absent in the honey bee. Many of the missing genes in both situations appear to have arisen recently in the Drosophila lineage, have single known functions in Drosophila, and act early in developmental pathways, while those that are preserved have pleiotropic functions. An evolutionary interpretation of these data is that either genes with multiple functions in a common ancestor are more likely to be preserved in both insect lineages, or genes that are preserved throughout evolution are more likely to co-opt additional functions.

  15. Analysis of gene order conservation in eukaryotes identifies transcriptionally and functionally linked genes.

    PubMed

    Dávila López, Marcela; Martínez Guerra, Juan José; Samuelsson, Tore

    2010-05-14

    The order of genes in eukaryotes is not entirely random. Studies of gene order conservation are important to understand genome evolution and to reveal mechanisms why certain neighboring genes are more difficult to separate during evolution. Here, genome-wide gene order information was compiled for 64 species, representing a wide variety of eukaryotic phyla. This information is presented in a browser where gene order may be displayed and compared between species. Factors related to non-random gene order in eukaryotes were examined by considering pairs of neighboring genes. The evolutionary conservation of gene pairs was studied with respect to relative transcriptional direction, intergenic distance and functional relationship as inferred by gene ontology. The results show that among gene pairs that are conserved the divergently and co-directionally transcribed genes are much more common than those that are convergently transcribed. Furthermore, highly conserved pairs, in particular those of fungi, are characterized by a short intergenic distance. Finally, gene pairs of metazoa and fungi that are evolutionary conserved and that are divergently transcribed are much more likely to be related by function as compared to poorly conserved gene pairs. One example is the ribosomal protein gene pair L13/S16, which is unusual as it occurs both in fungi and alveolates. A specific functional relationship between these two proteins is also suggested by the fact that they are part of the same operon in both eubacteria and archaea. In conclusion, factors associated with non-random gene order in eukaryotes include relative gene orientation, intergenic distance and functional relationships. It seems likely that certain pairs of genes are conserved because the genes involved have a transcriptional and/or functional relationship. The results also indicate that studies of gene order conservation aid in identifying genes that are related in terms of transcriptional control.

  16. Analysis of Gene Order Conservation in Eukaryotes Identifies Transcriptionally and Functionally Linked Genes

    PubMed Central

    Dávila López, Marcela; Martínez Guerra, Juan José; Samuelsson, Tore

    2010-01-01

    The order of genes in eukaryotes is not entirely random. Studies of gene order conservation are important to understand genome evolution and to reveal mechanisms why certain neighboring genes are more difficult to separate during evolution. Here, genome-wide gene order information was compiled for 64 species, representing a wide variety of eukaryotic phyla. This information is presented in a browser where gene order may be displayed and compared between species. Factors related to non-random gene order in eukaryotes were examined by considering pairs of neighboring genes. The evolutionary conservation of gene pairs was studied with respect to relative transcriptional direction, intergenic distance and functional relationship as inferred by gene ontology. The results show that among gene pairs that are conserved the divergently and co-directionally transcribed genes are much more common than those that are convergently transcribed. Furthermore, highly conserved pairs, in particular those of fungi, are characterized by a short intergenic distance. Finally, gene pairs of metazoa and fungi that are evolutionary conserved and that are divergently transcribed are much more likely to be related by function as compared to poorly conserved gene pairs. One example is the ribosomal protein gene pair L13/S16, which is unusual as it occurs both in fungi and alveolates. A specific functional relationship between these two proteins is also suggested by the fact that they are part of the same operon in both eubacteria and archaea. In conclusion, factors associated with non-random gene order in eukaryotes include relative gene orientation, intergenic distance and functional relationships. It seems likely that certain pairs of genes are conserved because the genes involved have a transcriptional and/or functional relationship. The results also indicate that studies of gene order conservation aid in identifying genes that are related in terms of transcriptional control. PMID:20498846

  17. Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte.

    PubMed

    Sonne, Si Brask; Almstrup, Kristian; Dalgaard, Marlene; Juncker, Agnieszka Sierakowska; Edsgard, Daniel; Ruban, Ludmila; Harrison, Neil J; Schwager, Christian; Abdollahi, Amir; Huber, Peter E; Brunak, Søren; Gjerdrum, Lise Mette; Moore, Harry D; Andrews, Peter W; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

    2009-06-15

    Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. We speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells.

  18. Evolutionary conservation of regulatory elements in vertebrate Hox gene clusters.

    PubMed

    Santini, Simona; Boore, Jeffrey L; Meyer, Axel

    2003-06-01

    Comparisons of DNA sequences among evolutionarily distantly related genomes permit identification of conserved functional regions in noncoding DNA. Hox genes are highly conserved in vertebrates, occur in clusters, and are uninterrupted by other genes. We aligned (PipMaker) the nucleotide sequences of the HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human, and mouse, which are separated by approximately 500 million years of evolution. In support of our approach, several identified putative regulatory elements known to regulate the expression of Hox genes were recovered. The majority of the newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac database). The regulatory intergenic regions located between the genes that are expressed most anteriorly in the embryo are longer and apparently more evolutionarily conserved than those at the other end of Hox clusters. Different presumed regulatory sequences are retained in either the Aalpha or Abeta duplicated Hox clusters in the fish lineages. This suggests that the conserved elements are involved in different gene regulatory networks and supports the duplication-deletion-complementation model of functional divergence of duplicated genes.

  19. Evolutionary Conservation of Regulatory Elements in Vertebrate Hox Gene Clusters

    PubMed Central

    Santini, Simona; Boore, Jeffrey L.; Meyer, Axel

    2003-01-01

    Comparisons of DNA sequences among evolutionarily distantly related genomes permit identification of conserved functional regions in noncoding DNA. Hox genes are highly conserved in vertebrates, occur in clusters, and are uninterrupted by other genes. We aligned (PipMaker) the nucleotide sequences of the HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human, and mouse, which are separated by approximately 500 million years of evolution. In support of our approach, several identified putative regulatory elements known to regulate the expression of Hox genes were recovered. The majority of the newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac database). The regulatory intergenic regions located between the genes that are expressed most anteriorly in the embryo are longer and apparently more evolutionarily conserved than those at the other end of Hox clusters. Different presumed regulatory sequences are retained in either the Aα or Aβ duplicated Hox clusters in the fish lineages. This suggests that the conserved elements are involved in different gene regulatory networks and supports the duplication-deletion-complementation model of functional divergence of duplicated genes. PMID:12799348

  20. [Effect of different transfection reagents and injection methods in mice testicular injection on the expression of exogenous gene].

    PubMed

    Dai, Jianjun; Li, Xiang; Wu, Caifeng; Zhang, Shushan; Zhang, Tingyu; Zhang, Defu

    2014-10-01

    The purpose of this study was to study the effect of three different transfection reagents (Lipofectamine™ LTX & PLUS™, Lipofectamine 2000 and Nano-PAMAM-D) and three different testicular injection methods (rete testicular injection, seminiferous tubules injection and testicular interstitial injection) on the efficiency of production transgenic mice. After the mixtures of plasmid DNA (pEFP-C1) and transfection reagent were injected with different testicular injection methods, the sperm density, vitality, positive sperm rates and PCR positive transgenic mice rate were examined 30 days after injection. The results showed that the damage degree from slight to serious of three transfection reagents was Lipofectamine™ LTX & PLUS™, Lipofectamine 2000, and PAMAM-D. The sperm positive rates with green fluorescence of these three groups were 35.65%±0.69%, 12.86%±0.35% and 10.04%±0.20%, respectively. The PCR positive rates of transgenic newborn mice were 29.17%, 13.70% and 5.88%, respectively. Among the groups of different testicular injection methods, the damage degree from slight to serious was rete testicular injection, seminiferous tubules injection, and testicular interstitial injection, whereas the sperm positive rates with green fluorescence were 35.13%, 15.13%, and 0%, respectively. The PCR positive rates of transgenic newborn mice among different testicular injection groups were 33.3%, 12.5%, and 0.0%. The combination of rete testicular injection and Lipofectamine™ LTX & PLUS™ had the lowest toxicity and highest transgenic efficiency in the production of transgenic mice.

  1. Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling.

    PubMed

    Siska, Peter J; Johnpulle, Romany A N; Zhou, Alice; Bordeaux, Jennifer; Kim, Ju Young; Dabbas, Bashar; Dakappagari, Naveen; Rathmell, Jeffrey C; Rathmell, W Kimryn; Morgans, Alicia K; Balko, Justin M; Johnson, Douglas B

    2017-01-01

    Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel). Publically available data sets were used to validate primary sample analyses. Nearly all samples had some degree of T-cell infiltration and immune checkpoint expression. Seminomas were associated with increased CD3(+) T-cell infiltration, decreased Regulatory T-cells, increased PD-L1, and increased PD-1/PD-L1 spatial interaction compared with non-seminomas using FIHC. Gene expression profiling confirmed these findings and also demonstrated increased expression of T-cell markers (e.g., IFNγ, and LAG3) and cancer/testis antigens (e.g., PRAME) in seminomas, whereas non-seminomas demonstrated high neutrophil and macrophage gene signatures. Irrespective of histology, advanced TGCT stage was associated with decreased T-cell and NK-cell signatures, while Treg, neutrophil, mast cell and macrophage signatures increased with advanced stage. Importantly, cancer/testis antigen, neutrophil, and CD8(+)/regulatory T-cell signatures correlated with recurrence free survival. Thus, deep immune characterization of TGCT using IHC and gene expression profiling identified activated T-cell infiltration which correlated with seminoma histology and good prognosis. These results may provide a rationale for testing of anti-PD-1/PD-L1 agents and suggest prognostic markers.

  2. Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

    PubMed Central

    Beyer, U; Krönung, S K; Leha, A; Walter, L; Dobbelstein, M

    2016-01-01

    The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression of a proapoptotic isoform of the tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors of histone deacetylases (HDACs) restore GTAp63 expression and give rise to apoptosis. We show here that numerous additional transcripts throughout the genome are driven by related ERV9-LTRs. 3' Rapid amplification of cDNA ends (3'RACE) was combined with next-generation sequencing to establish a large set of such mRNAs. HDAC inhibitors induce these ERV9-LTR-driven genes but not the LTRs from other ERVs. In particular, a transcript encoding the death receptor DR5 originates from an ERV9-LTR inserted upstream of the protein coding regions of the TNFRSF10B gene, and it shows an expression pattern similar to GTAp63. When treating testicular cancer cells with HDAC inhibitors as well as the death ligand TNF-related apoptosis-inducing ligand (TRAIL), rapid cell death was observed, which depended on TNFRSF10B expression. HDAC inhibitors also cooperate with cisplatin (cDDP) to promote apoptosis in testicular cancer cells. ERV9-LTRs not only drive a large set of human transcripts, but a subset of them acts in a proapoptotic manner. We propose that this avoids the survival of damaged germ cells. HDAC inhibition represents a strategy of restoring the expression of a class of ERV9-LTR-mediated genes in testicular cancer cells, thereby re-enabling tumor suppression. PMID:26024393

  3. Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death.

    PubMed

    Beyer, U; Krönung, S K; Leha, A; Walter, L; Dobbelstein, M

    2016-01-01

    The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression of a proapoptotic isoform of the tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors of histone deacetylases (HDACs) restore GTAp63 expression and give rise to apoptosis. We show here that numerous additional transcripts throughout the genome are driven by related ERV9-LTRs. 3' Rapid amplification of cDNA ends (3'RACE) was combined with next-generation sequencing to establish a large set of such mRNAs. HDAC inhibitors induce these ERV9-LTR-driven genes but not the LTRs from other ERVs. In particular, a transcript encoding the death receptor DR5 originates from an ERV9-LTR inserted upstream of the protein coding regions of the TNFRSF10B gene, and it shows an expression pattern similar to GTAp63. When treating testicular cancer cells with HDAC inhibitors as well as the death ligand TNF-related apoptosis-inducing ligand (TRAIL), rapid cell death was observed, which depended on TNFRSF10B expression. HDAC inhibitors also cooperate with cisplatin (cDDP) to promote apoptosis in testicular cancer cells. ERV9-LTRs not only drive a large set of human transcripts, but a subset of them acts in a proapoptotic manner. We propose that this avoids the survival of damaged germ cells. HDAC inhibition represents a strategy of restoring the expression of a class of ERV9-LTR-mediated genes in testicular cancer cells, thereby re-enabling tumor suppression.

  4. Intron conservation in the fragile X gene (FMR 1)

    SciTech Connect

    Panther, R.; Ostrowski, R.S.; Stoerker, J.

    1994-09-01

    The intron probe STB12.3 was used to search for conservation of the intron sequence corresponding to the PstI fragment located approximately 450 bp downstream of the end of the first exon of the fragile X (FMR 1) gene. Standard techniques for DNA extraction, isolation, restriction enzyme digestion, blotting and probing were employed. The probe STB12.3 that hybridizes to an intron sequence in the human MR 1 gene is 1.2 bp long. Our results demonstrated that the STB12.3 sequence is conserved across at least two Kindgoms. Specifically, we have observed cross-hybridization between STB12.3 and sequences in Drosophila, Apis and Saccharomyces. Hybridization was not observed in Triticum. Most surprising was our observation of intron hybridization in Drosophila since Annemieke et al. (1991) did not find FMR 1 exon conservation in Drosophila. Intron sequence conservation had been previously reported but only between closely related (same Order) species.

  5. Identification, characterization and target gene analysis of testicular microRNAs in the oriental fruit fly Bactrocera dorsalis.

    PubMed

    Tariq, K; Peng, W; Saccone, G; Zhang, H

    2016-02-01

    MicroRNAs (miRNAs) are small noncoding RNAs that regulate various diverse biological processes including insect spermatogenesis. The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive horticultural pests in East Asia and the Pacific region. Although developmental miRNA profiles of B. dorsalis have enriched our knowledge, specific testicular miRNAs in this dipteran species are unexplored. In this study, we identified miRNAs from B. dorsalis testes by deep sequencing, which provided an overview of miRNA expression during spermatogenesis. Small RNA libraries were constructed from the testes of fully mature (FM), immature (IM) and middle-aged (MA) adult flies of B. dorsalis. Small RNA sequencing and data analysis revealed 172 known and 78 novel miRNAs amongst these libraries. Pairwise comparisons of libraries led to the identification of 24, 15 and 14 differentially expressed miRNAs in FM vs. IM, FM vs. MA and IM vs. MA insects, respectively. Using a bioinformatic approach, we predicted 124 target genes against the 13 most differentially expressed miRNAs. Furthermore, the expression patterns of six randomly selected miRNAs (from the 13 most differentially expressed miRNAs) and their putative target genes (from the 124 predicted target genes) were analysed in the testis of B. dorsalis by quantitative real-time PCR, which showed that out of six, four tested miRNAs-mRNAs had an inverse expression pattern and are probably co-regulated. This study is the first comparative profile of the miRNA transcriptome in three developmental stages of the testis, and provides a useful resource for further studies on the role of miRNAs in spermatogenesis in B. dorsalis. © 2015 The Royal Entomological Society.

  6. The Ter Mutation In The Dead End Gene Causes Germ Cell Loss And Testicular Germ Cell Tumours

    SciTech Connect

    Youngren, Kirsten K.; Coveney, Douglas; Peng, Xiaoning; Bhattacharya, Chitralekha; Schmidt, Laura S.; Nickerson, Michael L.; Lamb, Bruce T.; Deng Jian Min; Behringer, Richard R.; Capel, Blanche; Rubin, Edward M.; Nadeau, Joseph H.; Matin, Angabin

    2005-01-01

    In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds1. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males2 4. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells2 6, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine t o uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.

  7. A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse.

    PubMed Central

    He, W W; Kumar, M V; Tindall, D J

    1991-01-01

    The testicular feminized (Tfm) mouse lacks completely androgen responsiveness; and therefore, is unique for studying the role of androgenic steroids in different biological processes. In order to understand the molecular basis of this mutation, 2.8 kilobases of cDNA encoding the Tfm mouse androgen receptor (AR) were amplified with a polymerase chain reaction (PCR) technique. No large deletion in the coding region of the Tfm mouse AR was detected. However, sequence analysis revealed a single base deletion in the coding region of the Tfm AR mRNA. This mutation, which is located in the amino-terminus domain of the receptor, is predicted to cause a frame-shift in translation resulting in a premature termination of AR synthesis at amino acid 412. In vitro translation studies of the recombinant wild type and Tfm AR's demonstrated that the Tfm AR cDNA failed to produce a full-length receptor. Furthermore, the Tfm AR was demonstrated to lack transcriptional activation capability by cotransfection experiments using the Tfm AR with a reporter plasmid of mouse mammary tumor virus long terminal repeat linked to the chloramphenicol acetyltransferase gene. These studies provide evidence of the molecular defect which causes androgen insensitivity in the Tfm mouse. Images PMID:2041777

  8. New insights for male infertility revealed by alterations in spermatic function and differential testicular expression of thyroid-related genes.

    PubMed

    Romano, Renata Marino; Gomes, Samantha Nascimento; Cardoso, Nathalia Carolina Scandolara; Schiessl, Larissa; Romano, Marco Aurelio; Oliveira, Claudio Alvarenga

    2017-02-01

    The impact of thyroid hormone (TH) disorders on male reproductive biology has been a controversial issue for many years. Recently, we reported that hypothyroid male rats have a disruption of the seminiferous epithelium, which may compromise spermatogenesis. To improve the understanding of the reproductive pathogenesis of hypothyroidism and hyperthyroidism, male Wistar rats that developed these dysfunctions in adulthood were used as an experimental model. We evaluated the sperm production, reserves, transit time, morphology, and functionality (acrosome integrity, plasma membrane integrity, and mitochondrial activity), and the testicular expression of the TH receptors (Thra1 and Thra2, Thrb1, and Thrb2), deiodinases (Dio2 and Dio3), and the Mct8 transporter (Slc16a2) were assessed by reverse transcription followed by real-time quantitative PCR (RT-qPCR). The results were evaluated statistically by ANOVA and Tukey HSD test (P < 0.05). Hypothyroidism decreased the total and daily sperm productions and increased the sperm transit time through the epididymis, while the sperm functionality was reduced in both thyroid dysfunctions. Regarding the modulation of gene expression in the testis, hypothyroidism increased the expression of Thra1 and decreased the expression of Dio3, and hyperthyroidism increased the expression of Slc16a2. The observed alterations in spermatic production and function and in the expression of the TH receptor, deiodinase, and the TH transporter are suggestive of TH participation in spermatogenesis in adulthood.

  9. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci

    PubMed Central

    Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  10. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci.

    PubMed

    Bahudhanapati, Harinath; Bhattacharya, Shashwati; Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species.

  11. Molecular identification of genes involved in testicular steroid synthesis and characterization of the response to gonadotropic stimulation in the Senegalese sole (Solea senegalensis) testis.

    PubMed

    Marín-Juez, Rubén; Castellana, Barbara; Manchado, Manuel; Planas, Josep V

    2011-05-15

    In male teleosts, testicular steroids are essential hormones for the regulation of spermatogenesis and their production is regulated by pituitary gonadotropins. In the Senegalese sole (Solea senegalensis), an economically important flatfish with semi-cystic and asynchronous spermatogenesis, the gonadotropic regulation of spermatogenesis, particularly regarding the production and regulation of testicular steroids, are not well understood. For this reason, we first cloned and characterized the response of several key genes for the production and action of testicular steroids to the in vivo administration of human chorionic gonadotropin (hCG) and, second, we investigated the transcriptomic effects of hCG in the Senegalese sole testis. We succeeded in cloning the full-length cDNAs for Steroidogenic Acute Regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-HSD and 20β-HSD and a partial cDNA for the nuclear progesterone receptor. In this study we also identified a transcript encoding a protein with homology to StAR, which we named StAR-like, that could represent a new member of the StAR-related lipid transfer (START) family. All the cloned genes were expressed in the testis and their expression levels were significantly increased by the in vivo administration of hCG. The plasma levels of testosterone and 11-ketotestosterone also increased in response to hCG administration, likely as a result of the induction of the expression of steroidogenic enzymes by hCG. Furthermore, gene expression analysis by microarray identified 90 differentially expressed genes in the testis in response to hCG administration, including genes potentially involved in steroidogenesis, progression of spermatogenesis and germ cell maturation and cytoskeletal organization. Our results have identified for the first time a number of key genes involved in the regulation of steroid production and spermatogenesis in the Senegalese sole testis that are under gonadotropic control

  12. Valinomycin biosynthetic gene cluster in Streptomyces: conservation, ecology and evolution.

    PubMed

    Matter, Andrea M; Hoot, Sara B; Anderson, Patrick D; Neves, Susana S; Cheng, Yi-Qiang

    2009-09-29

    Many Streptomyces strains are known to produce valinomycin (VLM) antibiotic and the VLM biosynthetic gene cluster (vlm) has been characterized in two independent isolates. Here we report the phylogenetic relationships of these strains using both parsimony and likelihood methods, and discuss whether the vlm gene cluster shows evidence of horizontal transmission common in natural product biosynthetic genes. Eight Streptomyces strains from around the world were obtained and sequenced for three regions of the two large nonribosomal peptide synthetase genes (vlm1 and vlm2) involved in VLM biosynthesis. The DNA sequences representing the vlm gene cluster are highly conserved among all eight environmental strains. The geographic distribution pattern of these strains and the strict congruence between the trees of the two vlm genes and the housekeeping genes, 16S rDNA and trpB, suggest vertical transmission of the vlm gene cluster in Streptomyces with no evidence of horizontal gene transfer. We also explored the relationship of the sequence of vlm genes to that of the cereulide biosynthetic genes (ces) found in Bacillus cereus and found them highly divergent from each other at DNA level (genetic distance values >or= 95.6%). It is possible that the vlm gene cluster and the ces gene cluster may share a relatively distant common ancestor but these two gene clusters have since evolved independently.

  13. The drug target genes show higher evolutionary conservation than non-target genes.

    PubMed

    Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-26

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

  14. Investigation of six testicular germ cell tumor susceptibility genes suggests a parent-of-origin effect in SPRY4.

    PubMed

    Karlsson, Robert; Andreassen, Kristine E; Kristiansen, Wenche; Aschim, Elin L; Bremnes, Roy M; Dahl, Olav; Fosså, Sophie D; Klepp, Olbjørn; Langberg, Carl W; Solberg, Arne; Tretli, Steinar; Magnusson, Patrik K E; Adami, Hans-Olov; Haugen, Trine B; Grotmol, Tom; Wiklund, Fredrik

    2013-08-15

    Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with testicular germ cell tumor (TGCT) risk in the genes ATF7IP, BAK1, DMRT1, KITLG, SPRY4 and TERT. In the present study, we validate these associations in a Scandinavian population, and explore effect modification by parental sex and differences in associations between the major histological subtypes seminoma and non-seminoma. A total of 118 SNPs in the six genes were genotyped in a population-based Swedish-Norwegian sample comprising 831 TGCT case-parent triads, 474 dyads, 712 singletons and 3919 population controls. Seven hundred and thirty-four additional SNPs were imputed using reference haplotypes from the 1000 genomes project. SNP-TGCT association was investigated using a likelihood-based association test for nuclear families and unrelated subjects implemented in the software package UNPHASED. Forward stepwise regression within each gene was applied to determine independent association signals. Effect modifications by parent-of-origin and effect differences between histological subtypes were explored. We observed strong association between SNPs in all six genes and TGCT (lowest P-value per gene: ATF7IP 6.2 × 10(-6); BAK1 2.1 × 10(-10); DMRT1 6.7 × 10(-25); KITLG 2.1 × 10(-48); SPRY4 1.4 × 10(-29); TERT 1.8 × 10(-18)). Stepwise regression indicated three independent signals for BAK1 and TERT, two for SPRY4 and one each for DMRT1, ATF7IP and KITLG. A significant parent-of-origin effect was observed for rs10463352 in SPRY4 (maternal odds ratio = 1.72, paternal odds ratio = 0.99, interaction P = 0.0013). No significant effect differences between seminomas and non-seminomas were found. In summary, we validated previously reported genetic associations with TGCT in a Scandinavian population, and observed suggestive evidence of a parent-of-origin effect in SPRY4.

  15. Seed collection success and failure in fraxinus gene conservation efforts

    Treesearch

    Joseph D. Zeleznik; Andrew J. David

    2017-01-01

    National seed collection and gene conservation programs have expanded in recent years, especially in response to pressure from non-native pests such as the emerald ash borer (Agrilus planipennis). Since 2008, we have been working with the U.S. Department of Agriculture Agricultural Research Service (USDA ARS) and USDA Forest Service (USDA FS) leading seed collection...

  16. Ex situ gene conservation for conifers in the Pacific Northwest.

    Treesearch

    Sara R. Lipow; J. Bradley St. Clair; G.R. Johnson

    2002-01-01

    Recently, a group of public and private organizations responsible for managing much of the timberland in western Oregon and Washington formed the Pacific Northwest forest tree Gene Conservation Group (GCG) to ensure that the evolutionary potential of important regional tree species is maintained. The group is first compiling data to evaluate the genetic resource status...

  17. Contributions of public gardens to tree gene conservation

    Treesearch

    P.A. Allenstein

    2017-01-01

    American Public Gardens Association, founded in 1940, represents over 600 member gardens spanning North America and 24 countries. Its diverse membership includes botanic gardens, arboreta, and other public gardens which contribute to tree gene conservation. Some maintain ex situ collections nationally accredited through the Association’s Plant Collections Network, a 21...

  18. Testicular cancer.

    PubMed

    Peckham, M

    1988-01-01

    Testicular cancer, which predominantly occurs in young men, has become increasingly common; it is presently the most common malignancy in men aged 20-34. Despite a lack of knowledge of aetiology, empirical advances, particularly in the management of patients with advanced disease, have been dramatic. Prior to the development of effective chemotherapy in the 1970s, less than 10% of men with metastatic non-seminomatous germ cell tumours were cured; nowadays approximately 90% of patients are potentially curable. The introduction of effective chemotherapy has led to a reappraisal of surgery and radiotherapy in the management of early stage disease and the introduction of a policy of surveillance in patients without evidence of metastases at the time of removal of the primary tumour. Following chemotherapy, surgery is required in approximately 25% of patients with advanced disease to excise residual masses, which in one-fifth of cases will show evidence of residual malignancy. In a proportion of patients, testicular cancer develops on a background of long-standing infertility, whereas in many men there is temporary oligospermia, despite a previous history of fertility. The majority of patients with prior evidence of spermatogenesis recover this function following chemotherapy and there is no evidence that children fathered by such patients have an increased risk of malformation. Despite physician optimism and excellent prospects for cure, significant psycho-social morbidity is associated with the diagnosis and treatment of testicular cancer. Factors contributing to this are being identified and will lead, hopefully, to the minimisation of such problems by appropriate intervention.

  19. Using intron position conservation for homology-based gene prediction

    PubMed Central

    Keilwagen, Jens; Wenk, Michael; Erickson, Jessica L.; Schattat, Martin H.; Grau, Jan; Hartung, Frank

    2016-01-01

    Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest. Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well. Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration. PMID:26893356

  20. Using intron position conservation for homology-based gene prediction.

    PubMed

    Keilwagen, Jens; Wenk, Michael; Erickson, Jessica L; Schattat, Martin H; Grau, Jan; Hartung, Frank

    2016-05-19

    Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest.Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well.Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Conserved Arrangement of Nested Genes at the Drosophila Gart Locus

    PubMed Central

    Henikoff, Steven; Eghtedarzadeh, Mohammad K.

    1987-01-01

    The Drosophila melanogaster Gart gene encodes three enzymatic activities in the pathway for purine de novo synthesis. Alternative processing of the primary transcript leads to the synthesis of two overlapping polypeptides. The coding sequence for both polypeptides is interrupted by an intron that contains a functional cuticle protein gene encoded on the opposite DNA strand. Here we show that this nested organization also exists at the homologous locus of a distantly related species, Drosophila pseudoobscura. In both species, the intronic cuticle gene is expressed in wandering larvae and in prepupae. Remarkably, there are 24 different highly conserved noncoding segments within the intron containing the cuticle gene. These are found upstream of the transcriptional start, at the 3' end, and even within the single intronic gene intron. Other introns in the purine gene, including the intron at which alternative processing occurs, show no such homologies. It seems likely that at least some of the conserved noncoding regions are involved in specifying the high level developmental expression of the cuticle gene. We discuss the possibility that shared cis-acting regulatory sites might enhance transcription of both genes and help explain their nested arrangement. PMID:3123310

  2. [Segmental testicular infarction].

    PubMed

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; de Pablo Cárdenas, A; Ruiz Ramo, M; Pinós Paul, M

    2006-02-01

    We report the case of a 47 years old man previously diagnosed of left hidrocele. After having a recent mild left testicular pain, an ultrasonografic study revealed a solid hipoecoic testicular lesion rounded by a big hidrocele, suggesting a testicular neoplasm. Radical inguinal orchiectomy was made and pathologic study showed segmental testicular infarction. No malignancy was found. We review the literature of the topic.

  3. Evolution of the functionally conserved DCC gene in birds

    PubMed Central

    Patthey, Cedric; Tong, Yong Guang; Tait, Christine Mary; Wilson, Sara Ivy

    2017-01-01

    Understanding the loss of conserved genes is critical for determining how phenotypic diversity is generated. Here we focus on the evolution of DCC, a gene that encodes a highly conserved neural guidance receptor. Disruption of DCC in animal models and humans results in major neurodevelopmental defects including commissural axon defects. Here we examine DCC evolution in birds, which is of particular interest as a major model system in neurodevelopmental research. We found the DCC containing locus was disrupted several times during evolution, resulting in both gene losses and faster evolution rate of salvaged genes. These data suggest that DCC had been lost independently twice during bird evolution, including in chicken and zebra finch, whereas it was preserved in many other closely related bird species, including ducks. Strikingly, we observed that commissural axon trajectory appeared similar regardless of whether DCC could be detected or not. We conclude that the DCC locus is susceptible to genomic instability leading to independent disruptions in different branches of birds and a significant influence on evolution rate. Overall, the phenomenon of loss or molecular evolution of a highly conserved gene without apparent phenotype change is of conceptual importance for understanding molecular evolution of key biological processes. PMID:28240293

  4. Evolution of the functionally conserved DCC gene in birds.

    PubMed

    Patthey, Cedric; Tong, Yong Guang; Tait, Christine Mary; Wilson, Sara Ivy

    2017-02-27

    Understanding the loss of conserved genes is critical for determining how phenotypic diversity is generated. Here we focus on the evolution of DCC, a gene that encodes a highly conserved neural guidance receptor. Disruption of DCC in animal models and humans results in major neurodevelopmental defects including commissural axon defects. Here we examine DCC evolution in birds, which is of particular interest as a major model system in neurodevelopmental research. We found the DCC containing locus was disrupted several times during evolution, resulting in both gene losses and faster evolution rate of salvaged genes. These data suggest that DCC had been lost independently twice during bird evolution, including in chicken and zebra finch, whereas it was preserved in many other closely related bird species, including ducks. Strikingly, we observed that commissural axon trajectory appeared similar regardless of whether DCC could be detected or not. We conclude that the DCC locus is susceptible to genomic instability leading to independent disruptions in different branches of birds and a significant influence on evolution rate. Overall, the phenomenon of loss or molecular evolution of a highly conserved gene without apparent phenotype change is of conceptual importance for understanding molecular evolution of key biological processes.

  5. DG-CST (Disease Gene Conserved Sequence Tags), a database of human–mouse conserved elements associated to disease genes

    PubMed Central

    Boccia, Angelo; Petrillo, Mauro; di Bernardo, Diego; Guffanti, Alessandro; Mignone, Flavio; Confalonieri, Stefano; Luzi, Lucilla; Pesole, Graziano; Paolella, Giovanni; Ballabio, Andrea; Banfi, Sandro

    2005-01-01

    The identification and study of evolutionarily conserved genomic sequences that surround disease-related genes is a valuable tool to gain insight into the functional role of these genes and to better elucidate the pathogenetic mechanisms of disease. We created the DG-CST (Disease Gene Conserved Sequence Tags) database for the identification and detailed annotation of human–mouse conserved genomic sequences that are localized within or in the vicinity of human disease-related genes. CSTs are defined as sequences that show at least 70% identity between human and mouse over a length of at least 100 bp. The database contains CST data relative to over 1088 genes responsible for monogenetic human genetic diseases or involved in the susceptibility to multifactorial/polygenic diseases. DG-CST is accessible via the internet at http://dgcst.ceinge.unina.it/ and may be searched using both simple and complex queries. A graphic browser allows direct visualization of the CSTs and related annotations within the context of the relative gene and its transcripts. PMID:15608249

  6. [Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and individuals with infertility associated with AZFc deletion of the Y chromosome].

    PubMed

    Nemtsova, M V; Ivkin, E V; Simonova, O A; Rudenko, V V; Chernykh, V B; Mikhaylenko, D S; Loran, O B

    2016-01-01

    Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to

  7. Gene expression ontogeny of spermatogenesis in the marmoset uncovers primate characteristics during testicular development.

    PubMed

    Lin, Zachary Yu-Ching; Hirano, Takamasa; Shibata, Shinsuke; Seki, Naomi M; Kitajima, Ryunosuke; Sedohara, Ayako; Siomi, Mikiko C; Sasaki, Erika; Siomi, Haruhiko; Imamura, Masanori; Okano, Hideyuki

    2015-04-01

    Mammalian spermatogenesis has been investigated extensively in rodents and a strictly controlled developmental process has been defined at cellular and molecular levels. In comparison, primate spermatogenesis has been far less well characterized. However, important differences between primate and rodent spermatogenesis are emerging so it is not always accurate to extrapolate findings in rodents to primate systems. Here, we performed an extensive immunofluorescence study of spermatogenesis in neonatal, juvenile, and adult testes in the common marmoset (Callithrix jacchus) to determine primate-specific patterns of gene expression that underpin primate germ cell development. Initially we characterized adult spermatogonia into two main classes; mitotically active C-KIT(+)Ki67(+) cells and mitotically quiescent SALL4(+)PLZF(+)LIN28(+)DPPA4(+) cells. We then explored the expression of a set of markers, including PIWIL1/MARWI, VASA, DAZL, CLGN, RanBPM, SYCP1 and HAPRIN, during germ cell differentiation from early spermatocytes through round and elongating spermatids, and a clear program of gene expression changes was determined as development proceeded. We then examined the juvenile marmoset testis. Markers of gonocytes demonstrated two populations; one that migrates to the basal membrane where they form the SALL4(+) or C-KIT(+) spermatogonia, and another that remains in the lumen of the seminiferous tubule. This later population, historically identified as pre-spermatogonia, expressed meiotic and apoptotic markers and were eliminated because they appear to have failed to correctly migrate. Our findings provide the first platform of gene expression dynamics in adult and developing germ cells of the common marmoset. Although we have characterized a limited number of genes, these results will facilitate primate spermatogenesis research and understanding of human reproduction.

  8. Conservation of Gbx genes from EHG homeobox in bivalve molluscs.

    PubMed

    Mesías-Gansbiller, Crimgilt; Sánchez, José L; Pazos, Antonio J; Lozano, Vanessa; Martínez-Escauriaza, Roi; Luz Pérez-Parallé, M

    2012-04-01

    Homeobox-containing genes encode a set of transcription factors that have been shown to control spatial patterning mechanisms in bilaterian organism development. The homeobox gene Gbx, included in the EHGbox cluster, is implicated in the development of the nervous system. In this study, we surveyed five different families of Bivalvia for the presence of Gbx genes by means of PCR with degenerate primers. We were able to recover seven Gbx gene fragments from five bivalve species: Solen marginatus, Mimachlamys varia, Venerupis pullastra, Ostrea edulis and Mytilus galloprovincialis (the derived amino acid sequence were designated Sma-Gbx, Cva-Gbx, Vpu-Gbx, Oed-Gbx and Mga-Gbx, respectively). These genes are orthologous to various Gbx genes present in bilaterian genomes. The Gbx genes in four Bivalvia families, namely Solenidae, Veneridae, Ostreidae and Mytilidae, are newly reported here and we also showed additional information of the Gbx genes of Pectinidae. The phylogenetic analyses by neighbour-joining, UPGMA, maximum parsimony and Bayesian analysis clearly indicated that the Gbx sequences formed a well supported clade and assigned these Gbx genes to the Gbx family. These data permit to confirm that the homeodomain of the Gbx family is highly conserved among these five distinct families of bivalve molluscs. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Gene essentiality, conservation index and co-evolution of genes in cyanobacteria.

    PubMed

    Tiruveedula, Gopi Siva Sai; Wangikar, Pramod P

    2017-01-01

    Cyanobacteria, a group of photosynthetic prokaryotes, dominate the earth with ~ 1015 g wet biomass. Despite diversity in habitats and an ancient origin, cyanobacterial phylum has retained a significant core genome. Cyanobacteria are being explored for direct conversion of solar energy and carbon dioxide into biofuels. For this, efficient cyanobacterial strains will need to be designed via metabolic engineering. This will require identification of target knockouts to channelize the flow of carbon toward the product of interest while minimizing deletions of essential genes. We propose "Gene Conservation Index" (GCI) as a quick measure to predict gene essentiality in cyanobacteria. GCI is based on phylogenetic profile of a gene constructed with a reduced dataset of cyanobacterial genomes. GCI is the percentage of organism clusters in which the query gene is present in the reduced dataset. Of the 750 genes deemed to be essential in the experimental study on S. elongatus PCC 7942, we found 494 to be conserved across the phylum which largely comprise of the essential metabolic pathways. On the contrary, the conserved but non-essential genes broadly comprise of genes required under stress conditions. Exceptions to this rule include genes such as the glycogen synthesis and degradation enzymes, deoxyribose-phosphate aldolase (DERA), glucose-6-phosphate 1-dehydrogenase (zwf) and fructose-1,6-bisphosphatase class1, which are conserved but non-essential. While the essential genes are to be avoided during gene knockout studies as potentially lethal deletions, the non-essential but conserved set of genes could be interesting targets for metabolic engineering. Further, we identify clusters of co-evolving genes (CCG), which provide insights that may be useful in annotation. Principal component analysis (PCA) plots of the CCGs are demonstrated as data visualization tools that are complementary to the conventional heatmaps. Our dataset consists of phylogenetic profiles for 23

  10. The importance of gene conservation in the USDA Forest Service

    Treesearch

    Robert D. Mangold

    2017-01-01

    Aldo Leopold once said “to keep every cog and wheel is the first precaution of intelligent tinkering.” The USDA Forest Service has embarked on a long-term effort to do just that. Our gene conservation efforts in forest trees are a modest beginning to this urgent need. In the early 2000s, the Forest Health Protection Program and its partners in the National Forest...

  11. Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila

    PubMed Central

    Oortveld, Merel A. W.; Keerthikumar, Shivakumar; Oti, Martin; Nijhof, Bonnie; Fernandes, Ana Clara; Kochinke, Korinna; Castells-Nobau, Anna; van Engelen, Eva; Ellenkamp, Thijs; Eshuis, Lilian; Galy, Anne; van Bokhoven, Hans; Habermann, Bianca; Brunner, Han G.; Zweier, Christiane; Verstreken, Patrik; Huynen, Martijn A.; Schenck, Annette

    2013-01-01

    Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules. PMID:24204314

  12. Simvastatin and Dipentyl Phthalate Lower Ex vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat

    EPA Science Inventory

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/transport, and...

  13. Simvastatin and Dipentyl Phthalate Lower Ex vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat

    EPA Science Inventory

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/transport, and...

  14. Evolutionary Conservation of Ceratitis capitata transformer Gene Function

    PubMed Central

    Pane, Attilio; De Simone, Annamaria; Saccone, Giuseppe; Polito, Catello

    2005-01-01

    Transformer functions as a binary switch gene in the sex determination and sexual differentiation of Drosophila melanogaster and Ceratitis capitata, two insect species that separated nearly 100 million years ago. The TRA protein is required for female differentiation of XX individuals, while XY individuals express smaller, presumably nonfunctional TRA peptides and consequently develop into adult males. In both species, tra confers female sexual identity through a well-conserved double-sex gene. However, unlike Drosophila tra, which is regulated by the upstream Sex-lethal gene, Ceratitis tra itself is likely to control a feedback loop that ensures the maintenance of the female sexual state. The putative CcTRA protein shares a very low degree of sequence identity with the TRA proteins from Drosophila species. However, in this study we show that a female-specific Ceratitis Cctra cDNA encoding the putative full-length CcTRA protein is able to support the female somatic and germline sexual differentiation of D. melanogaster XX; tra mutant adults. Although highly divergent, CcTRA can functionally substitute for DmTRA and induce the female-specific expression of both Dmdsx and Dmfru genes. These data demonstrate the unusual plasticity of the TRA protein that retains a conserved function despite the high evolutionary rate. We suggest that transformer plays an important role in providing a molecular basis for the variety of sex-determining systems seen among insects. PMID:15998727

  15. Evolutionary conservation and diversification of Rh family genes and proteins

    PubMed Central

    Huang, Cheng-Han; Peng, Jianbin

    2005-01-01

    Rhesus (Rh) proteins were first identified in human erythroid cells and recently in other tissues. Like ammonia transporter (Amt) proteins, their only homologues, Rh proteins have the 12 transmembrane-spanning segments characteristic of transporters. Many think Rh and Amt proteins transport the same substrate, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\mathrm{NH}}_{3}/{\\mathrm{NH}}_{4}^{+}\\end{equation*}\\end{document}, whereas others think that Rh proteins transport CO2 and Amt proteins NH3. In the latter view, Rh and Amt are different biological gas channels. To reconstruct the phylogeny of the Rh family and study its coexistence with and relationship to Amt in depth, we analyzed 111 Rh genes and 260 Amt genes. Although Rh and Amt are found together in organisms as diverse as unicellular eukaryotes and sea squirts, Rh genes apparently arose later, because they are rare in prokaryotes. However, Rh genes are prominent in vertebrates, in which Amt genes disappear. In organisms with both types of genes, Rh had apparently diverged away from Amt rapidly and then evolved slowly over a long period. Functionally divergent amino acid sites are clustered in transmembrane segments and around the gas-conducting lumen recently identified in Escherichia coli AmtB, in agreement with Rh proteins having new substrate specificity. Despite gene duplications and mutations, the Rh paralogous groups all have apparently been subject to strong purifying selection indicating functional conservation. Genes encoding the classical Rh proteins in mammalian red cells show higher nucleotide substitution rates at nonsynonymous codon positions than other Rh genes, a finding that suggests a possible role for these proteins in red cell morphogenetic evolution. PMID:16227429

  16. Evolutionary conservation and diversification of Rh family genes and proteins.

    PubMed

    Huang, Cheng-Han; Peng, Jianbin

    2005-10-25

    Rhesus (Rh) proteins were first identified in human erythroid cells and recently in other tissues. Like ammonia transporter (Amt) proteins, their only homologues, Rh proteins have the 12 transmembrane-spanning segments characteristic of transporters. Many think Rh and Amt proteins transport the same substrate, NH(3)/NH(4)(+), whereas others think that Rh proteins transport CO(2) and Amt proteins NH(3). In the latter view, Rh and Amt are different biological gas channels. To reconstruct the phylogeny of the Rh family and study its coexistence with and relationship to Amt in depth, we analyzed 111 Rh genes and 260 Amt genes. Although Rh and Amt are found together in organisms as diverse as unicellular eukaryotes and sea squirts, Rh genes apparently arose later, because they are rare in prokaryotes. However, Rh genes are prominent in vertebrates, in which Amt genes disappear. In organisms with both types of genes, Rh had apparently diverged away from Amt rapidly and then evolved slowly over a long period. Functionally divergent amino acid sites are clustered in transmembrane segments and around the gas-conducting lumen recently identified in Escherichia coli AmtB, in agreement with Rh proteins having new substrate specificity. Despite gene duplications and mutations, the Rh paralogous groups all have apparently been subject to strong purifying selection indicating functional conservation. Genes encoding the classical Rh proteins in mammalian red cells show higher nucleotide substitution rates at nonsynonymous codon positions than other Rh genes, a finding that suggests a possible role for these proteins in red cell morphogenetic evolution.

  17. Testicular Sonogram

    PubMed Central

    Devkota, Jagadishwar; White, Sherry

    1980-01-01

    Precise localization, detection, and recognition of minor changes in testicular lesions are important because teratocarcinoma is notorious for manifesting as secondaries at the time the primary site is obvious to the clinician. In the past, questionable enlargement of the testis due to significant pathology required numerous radiographic invasive special procedures to provide a correct diagnosis. Due to the advent of the sophisticated digital ultrasound imager with high frequency quarter wave transducer, it is possible to detect minor changes in the tissue character of the testis, thus enabling the physician to tackle primary neoplasms prior to distant spread. In our case we were able to detect the abnormality in the testis, but unfortunately a large secondary abnormal mass was present. Even at that stage we were able to map out the extent of the lesion which was beneficial to the surgeon and the patient. Ultrasound studies were utilized in serial follow-up studies. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:7401191

  18. Comparing the evolutionary conservation between human essential genes, human orthologs of mouse essential genes and human housekeeping genes.

    PubMed

    Lv, Wenhua; Zheng, Jiajia; Luan, Meiwei; Shi, Miao; Zhu, Hongjie; Zhang, Mingming; Lv, Hongchao; Shang, Zhenwei; Duan, Lian; Zhang, Ruijie; Jiang, Yongshuai

    2015-11-01

    Human housekeeping genes are often confused with essential human genes, and several studies regard both types of genes as having the same level of evolutionary conservation. However, this is not necessarily the case. To clarify this, we compared the differences between human housekeeping genes and essential human genes with respect to four aspects: the evolutionary rate (dN/dS), protein sequence identity, single-nucleotide polymorphism (SNP) density and level of linkage disequilibrium (LD). The results showed that housekeeping genes had lower evolutionary rates, higher sequence identities, lower SNP densities and higher levels of LD compared with essential genes. Together, these findings indicate that housekeeping and essential genes are two distinct types of genes, and that housekeeping genes have a higher level of evolutionary conservation. Therefore, we suggest that researchers should pay careful attention to the distinctions between housekeeping genes and essential genes. Moreover, it is still controversial whether we should substitute human orthologs of mouse essential genes for human essential genes. Therefore, we compared the evolutionary features between human orthologs of mouse essential genes and human housekeeping genes and we got inconsistent results in long-term and short-term evolutionary characteristics implying the irrationality of simply replacing human essential genes with human orthologs of mouse essential genes.

  19. Patterns of intron gain and conservation in eukaryotic genes

    PubMed Central

    Carmel, Liran; Rogozin, Igor B; Wolf, Yuri I; Koonin, Eugene V

    2007-01-01

    Background: The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions. Results: We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only ~8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs. Conclusion: We obtained robust estimates of the contribution of parallel gain to the observed sharing of intron positions

  20. Pediatric Testicular Torsion.

    PubMed

    Bowlin, Paul R; Gatti, John M; Murphy, J Patrick

    2017-02-01

    The pediatric patient presenting with acute scrotal pain requires prompt evaluation and management given the likelihood of testicular torsion as the underlying cause. Although other diagnoses can present with acute testicular pain, it is important to recognize the possibility of testicular torsion because the best chance of testicular preservation occurs with expeditious management. When testicular torsion is suspected, prompt surgical exploration is warranted. A delay in surgical management should not occur in an effort to obtain confirmatory imaging. When torsion is discovered, the contralateral testicle should undergo fixation to reduce the risk of asynchronous torsion.

  1. The gsdf gene locus harbors evolutionary conserved and clustered genes preferentially expressed in fish previtellogenic oocytes.

    PubMed

    Gautier, Aude; Le Gac, Florence; Lareyre, Jean-Jacques

    2011-02-01

    The gonadal soma-derived factor (GSDF) belongs to the transforming growth factor-β superfamily and is conserved in teleostean fish species. Gsdf is specifically expressed in the gonads, and gene expression is restricted to the granulosa and Sertoli cells in trout and medaka. The gsdf gene expression is correlated to early testis differentiation in medaka and was shown to stimulate primordial germ cell and spermatogonia proliferation in trout. In the present study, we show that the gsdf gene localizes to a syntenic chromosomal fragment conserved among vertebrates although no gsdf-related gene is detected on the corresponding genomic region in tetrapods. We demonstrate using quantitative RT-PCR that most of the genes localized in the synteny are specifically expressed in medaka gonads. Gsdf is the only gene of the synteny with a much higher expression in the testis compared to the ovary. In contrast, gene expression pattern analysis of the gsdf surrounding genes (nup54, aff1, klhl8, sdad1, and ptpn13) indicates that these genes are preferentially expressed in the female gonads. The tissue distribution of these genes is highly similar in medaka and zebrafish, two teleostean species that have diverged more than 110 million years ago. The cellular localization of these genes was determined in medaka gonads using the whole-mount in situ hybridization technique. We confirm that gsdf gene expression is restricted to Sertoli and granulosa cells in contact with the premeiotic and meiotic cells. The nup54 gene is expressed in spermatocytes and previtellogenic oocytes. Transcripts corresponding to the ovary-specific genes (aff1, klhl8, and sdad1) are detected only in previtellogenic oocytes. No expression was detected in the gonocytes in 10 dpf embryos. In conclusion, we show that the gsdf gene localizes to a syntenic chromosomal fragment harboring evolutionary conserved genes in vertebrates. These genes are preferentially expressed in previtelloogenic oocytes, and thus, they

  2. Deep evolutionary conservation of autism-related genes.

    PubMed

    Shpigler, Hagai Y; Saul, Michael C; Corona, Frida; Block, Lindsey; Cash Ahmed, Amy; Zhao, Sihai D; Robinson, Gene E

    2017-09-05

    E. O. Wilson proposed in Sociobiology that similarities between human and animal societies reflect common mechanistic and evolutionary roots. When introduced in 1975, this controversial hypothesis was beyond science's ability to test. We used genomic analyses to determine whether superficial behavioral similarities in humans and the highly social honey bee reflect common molecular mechanisms. Here, we report that gene expression signatures for individual bees unresponsive to various salient social stimuli are significantly enriched for autism spectrum disorder-related genes. These signatures occur in the mushroom bodies, a high-level integration center of the insect brain. Furthermore, our finding of enrichment was unique to autism spectrum disorders; brain gene expression signatures from other honey bee behaviors do not show this enrichment, nor do datasets from other human behavioral and health conditions. These results demonstrate deep conservation for genes associated with a human social pathology and individual differences in insect social behavior, thus providing an example of how comparative genomics can be used to test sociobiological theory.

  3. The Evolution of Novelty in Conserved Gene Families

    PubMed Central

    Markov, Gabriel V.; Sommer, Ralf J.

    2012-01-01

    One of the major aims of contemporary evolutionary biology is the understanding of the current pattern of biological diversity. This involves, first, the description of character distribution at various nodes of the phylogenetic tree of life and, second, the functional explanation of such changes. The analysis of character distribution is a powerful tool at both the morphological and molecular levels. Recent high-throughput sequencing approaches provide new opportunities to study the genetic architecture of organisms at the genome-wide level. In eukaryotes, one overarching finding is the absence of simple correlations of gene count and biological complexity. Instead, the domain architecture of proteins is becoming a central focus for large-scale evolutionary innovations. Here, we review examples of the evolution of novelty in conserved gene families in insects and nematodes. We highlight how in the absence of whole-genome duplications molecular novelty can arise, how members of gene families have diversified at distinct mechanistic levels, and how gene expression can be maintained in the context of multiple innovations in regulatory mechanisms. PMID:22779028

  4. Evolutionary conservation and disease gene association of the human genes composing pseudogenes.

    PubMed

    Sen, Kamalika; Ghosh, Tapash Chandra

    2012-06-15

    Pseudogenes, the 'genomic fossils' present portrayal of evolutionary history of human genome. The human genes configuring pseudogenes are also now coming forth as important resources in the study of human protein evolution. In this communication, we explored evolutionary conservation of the genes forming pseudogenes over the genes lacking any pseudogene and delving deeper, we probed an evolutionary rate difference between the disease genes in the two groups. We illustrated this differential evolutionary pattern by gene expressivity, number of regulatory miRNA targeting per gene, abundance of protein complex forming genes and lesser percentage of protein intrinsic disorderness. Furthermore, pseudogenes are observed to harbor sequence variations, over their entirety, those become degenerative disease-causing mutations though the disease involvement of their progenitors is still unexplored. Here, we unveiled an immense association of disease genes in the genes casting pseudogenes in human. We interpreted the issue by disease associated miRNA targeting, genes containing polymorphisms in miRNA target sites, abundance of genes having disease causing non-synonymous mutations, disease gene specific network properties, presence of genes having repeat regions, affluence of dosage sensitive genes and the presence of intrinsically unstructured protein regions.

  5. Regulation of photoreceptor gene transcription via a highly conserved transcriptional regulatory element by vsx gene products

    PubMed Central

    Pan, Yi; Comiskey, Daniel F.; Kelly, Lisa E.; Chandler, Dawn S.

    2016-01-01

    Purpose The photoreceptor conserved element-1 (PCE-1) sequence is found in the transcriptional regulatory regions of many genes expressed in photoreceptors. The retinal homeobox (Rx or Rax) gene product functions by binding to PCE-1 sites. However, other transcriptional regulators have also been reported to bind to PCE-1. One of these, vsx2, is expressed in retinal progenitor and bipolar cells. The purpose of this study is to identify Xenopus laevis vsx gene products and characterize vsx gene product expression and function with respect to the PCE-1 site. Methods X. laevis vsx gene products were amplified with PCR. Expression patterns were determined with in situ hybridization using whole or sectioned X. laevis embryos and digoxigenin- or fluorescein-labeled antisense riboprobes. DNA binding characteristics of the vsx gene products were analyzed with electrophoretic mobility shift assays (EMSAs) using in vitro translated proteins and radiolabeled oligonucleotide probes. Gene transactivation assays were performed using luciferase-based reporters and in vitro transcribed effector gene products, injected into X. laevis embryos. Results We identified one vsx1 and two vsx2 gene products. The two vsx2 gene products are generated by alternate mRNA splicing. We verified that these gene products are expressed in the developing retina and that expression resolves into distinct cell types in the mature retina. Finally, we found that vsx gene products can bind the PCE-1 site in vitro and that the two vsx2 isoforms have different gene transactivation activities. Conclusions vsx gene products are expressed in the developing and mature neural retina. vsx gene products can bind the PCE-1 site in vitro and influence the expression of a rhodopsin promoter-luciferase reporter gene. The two isoforms of vsx have different gene transactivation activities in this reporter gene system. PMID:28003732

  6. A case of Carney complex presenting as acute testicular pain

    PubMed Central

    Alleemudder, Adam; Pillai, Rajiv

    2016-01-01

    We describe the case of a 7-year-old boy who presented with testicular pain but was found to have bilateral testicular lesions later confirmed as Sertoli cell tumors. Genetic testing confirmed a PRKAR1A gene mutation consistent with Carney complex, a rare genetic disorder characterized by skin lesions, myxomas, and multiple endocrine neoplasms. A review of the condition is made highlighting the association with testicular tumors, particularly of Sertoli cell origin. PMID:27453662

  7. Conserved Gene Expression Programs in Developing Roots from Diverse Plants

    PubMed Central

    Huang, Ling; Schiefelbein, John

    2015-01-01

    The molecular basis for the origin and diversification of morphological adaptations is a central issue in evolutionary developmental biology. Here, we defined temporal transcript accumulation in developing roots from seven vascular plants, permitting a genome-wide comparative analysis of the molecular programs used by a single organ across diverse species. The resulting gene expression maps uncover significant similarity in the genes employed in roots and their developmental expression profiles. The detailed analysis of a subset of 133 genes known to be associated with root development in Arabidopsis thaliana indicates that most of these are used in all plant species. Strikingly, this was also true for root development in a lycophyte (Selaginella moellendorffii), which forms morphologically different roots and is thought to have evolved roots independently. Thus, despite vast differences in size and anatomy of roots from diverse plants, the basic molecular mechanisms employed during root formation appear to be conserved. This suggests that roots evolved in the two major vascular plant lineages either by parallel recruitment of largely the same developmental program or by elaboration of an existing root program in the common ancestor of vascular plants. PMID:26265761

  8. Conserved Gene Expression Programs in Developing Roots from Diverse Plants.

    PubMed

    Huang, Ling; Schiefelbein, John

    2015-08-01

    The molecular basis for the origin and diversification of morphological adaptations is a central issue in evolutionary developmental biology. Here, we defined temporal transcript accumulation in developing roots from seven vascular plants, permitting a genome-wide comparative analysis of the molecular programs used by a single organ across diverse species. The resulting gene expression maps uncover significant similarity in the genes employed in roots and their developmental expression profiles. The detailed analysis of a subset of 133 genes known to be associated with root development in Arabidopsis thaliana indicates that most of these are used in all plant species. Strikingly, this was also true for root development in a lycophyte (Selaginella moellendorffii), which forms morphologically different roots and is thought to have evolved roots independently. Thus, despite vast differences in size and anatomy of roots from diverse plants, the basic molecular mechanisms employed during root formation appear to be conserved. This suggests that roots evolved in the two major vascular plant lineages either by parallel recruitment of largely the same developmental program or by elaboration of an existing root program in the common ancestor of vascular plants.

  9. Functional conservation of the Drosophila hybrid incompatibility gene Lhr

    PubMed Central

    2011-01-01

    Background Hybrid incompatibilities such as sterility and lethality are commonly modeled as being caused by interactions between two genes, each of which has diverged separately in one of the hybridizing lineages. The gene Lethal hybrid rescue (Lhr) encodes a rapidly evolving heterochromatin protein that causes lethality of hybrid males in crosses between Drosophila melanogaster females and D. simulans males. Previous genetic analyses showed that hybrid lethality is caused by D. simulans Lhr but not by D. melanogaster Lhr, confirming a critical prediction of asymmetry in the evolution of a hybrid incompatibility gene. Results Here we have examined the functional properties of Lhr orthologs from multiple Drosophila species, including interactions with other heterochromatin proteins, localization to heterochromatin, and ability to complement hybrid rescue in D. melanogaster/D. simulans hybrids. We find that these properties are conserved among most Lhr orthologs, including Lhr from D. melanogaster, D. simulans and the outgroup species D. yakuba. Conclusions We conclude that evolution of the hybrid lethality properties of Lhr between D. melanogaster and D. simulans did not involve extensive loss or gain of functions associated with protein interactions or localization to heterochromatin. PMID:21366928

  10. Conserved gene regulation during acute inflammation between zebrafish and mammals.

    PubMed

    Forn-Cuní, G; Varela, M; Pereiro, P; Novoa, B; Figueras, A

    2017-02-03

    Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress. We provide evidence that immune signaling pathways and single gene expression is well conserved throughout evolution and that the zebrafish and mammal acute genomic responses after lipopolysaccharide stimulation are highly correlated despite the differential susceptibility between species to that compound. Therefore, we formally confirm that zebrafish inflammatory models are suited to study the basic mechanisms of inflammation in human inflammatory diseases, with great translational impact potential.

  11. Do We Know What Causes Testicular Cancer?

    MedlinePlus

    ... Factors, and Prevention Do We Know What Causes Testicular Cancer? The exact cause of most testicular cancers is ... Cancer? Can Testicular Cancer Be Prevented? More In Testicular Cancer About Testicular Cancer Causes, Risk Factors, and Prevention ...

  12. What Happens After Treatment for Testicular Cancer?

    MedlinePlus

    ... Cancer After Treatment What Happens After Treatment for Testicular Cancer? For most people with testicular cancer, treatment removes ... Treatment for Testicular Cancer Stops Working More In Testicular Cancer About Testicular Cancer Causes, Risk Factors, and Prevention ...

  13. The sex-determining factors SRY and SOX9 regulate similar target genes and promote testis cord formation during testicular differentiation.

    PubMed

    Li, Yunmin; Zheng, Ming; Lau, Yun-Fai Chris

    2014-08-07

    Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/β-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates common targets and activates its own gene regulatory program, beyond SRY actions, in sex determination.

  14. A conserved noncoding sequence can function as a spermatocyte-specific enhancer and a bidirectional promoter for a ubiquitously expressed gene and a testis-specific long noncoding RNA.

    PubMed

    Kurihara, Misuzu; Shiraishi, Akira; Satake, Honoo; Kimura, Atsushi P

    2014-08-26

    Tissue-specific gene expression is tightly regulated by various elements such as promoters, enhancers, and long noncoding RNAs (lncRNAs). In the present study, we identified a conserved noncoding sequence (CNS1) as a novel enhancer for the spermatocyte-specific mouse testicular cell adhesion molecule 1 (Tcam1) gene. CNS1 was located 3.4kb upstream of the Tcam1 gene and associated with histone H3K4 mono-methylation in testicular germ cells. By the in vitro reporter gene assay, CNS1 could enhance Tcam1 promoter activity only in GC-2spd(ts) cells, which were derived from mouse spermatocytes. When we integrated the 6.9-kb 5'-flanking sequence of Tcam1 with or without a deletion of CNS1 linked to the enhanced green fluorescent protein gene into the chromatin of GC-2spd(ts) cells, CNS1 significantly enhanced Tcam1 promoter activity. These results indicate that CNS1 could function as a spermatocyte-specific enhancer. Interestingly, CNS1 also showed high bidirectional promoter activity in the reporter assay, and consistent with this, the Smarcd2 gene and lncRNA, designated lncRNA-Tcam1, were transcribed from adjacent regions of CNS1. While Smarcd2 was ubiquitously expressed, lncRNA-Tcam1 expression was restricted to testicular germ cells, although this lncRNA did not participate in Tcam1 activation. Ubiquitous Smarcd2 expression was correlated to CpG hypo-methylation of CNS1 and partially controlled by Sp1. However, for lncRNA-Tcam1 transcription, the strong association with histone acetylation and histone H3K4 tri-methylation also appeared to be required. The present data suggest that CNS1 is a spermatocyte-specific enhancer for the Tcam1 gene and a bidirectional promoter of Smarcd2 and lncRNA-Tcam1. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Cytochrome b gene for species identification of the conservation animals.

    PubMed

    Hsieh, H M; Chiang, H L; Tsai, L C; Lai, S Y; Huang, N E; Linacre, A; Lee, J C

    2001-10-15

    A partial DNA sequence of cytochrome b gene was used to identify the remains of endangered animals and species endemic to Taiwan. The conservation of animals species included in this study were: the formosan gem-faced civets, leopard cats, tigers, clouded leopards, lion, formosan muntjacs, formosan sika deers, formosan sambars, formosan serows, water buffalo, formosan pangolins and formosan macaques. The control species used included domestic cats, domestic dogs, domestic sheeps, domestic cattles, domestic pigs and humans. Heteroplasmy was detected in the formosan macaque, domestic pig and domestic cats. The frequencies of heteroplasmy in these animals were about 0.25% (1 in 402bp). Sequences were aligned by Pileup program of GCG computer package, and the phylogenetic tree was constructed by the neighbor-joining method. The results of sequence comparison showed that the percentage range of sequence diversity in the same species was from 0.25 to 2.74%, and that between the different species was from 5.97 to 34.83%. The results of phylogenetic analysis showed that the genetic distance between the different species was from 6.33 to 40.59. Animals of the same species, both the endangered animal species and domestic animals, were clustered together in the neighbor-joining tree. Three unknown samples of animal remains were identified by this system. The partial sequence of cytochrome b gene adopted in this study proved to be usable for animal identification.

  16. PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES

    SciTech Connect

    V, DE CRECY-LAGARD; D, HANSON A

    2012-01-03

    Identifying functions for all gene products in all sequenced organisms is a central challenge of the post-genomic era. However, at least 30-50% of the proteins encoded by any given genome are of unknown function, or wrongly or vaguely annotated. Many of these 'unknown' proteins are common to prokaryotes and plants. We accordingly set out to predict and experimentally test the functions of such proteins. Our approach to functional prediction is integrative, coupling the extensive post-genomic resources available for plants with comparative genomics based on hundreds of microbial genomes, and functional genomic datasets from model microorganisms. The early phase is computer-assisted; later phases incorporate intellectual input from expert plant and microbial biochemists. The approach thus bridges the gap between automated homology-based annotations and the classical gene discovery efforts of experimentalists, and is much more powerful than purely computational approaches to identifying gene-function associations. Among Arabidopsis genes, we focused on those (2,325 in total) that (i) are unique or belong to families with no more than three members, (ii) are conserved between plants and prokaryotes, and (iii) have unknown or poorly known functions. Computer-assisted selection of promising targets for deeper analysis was based on homology .. independent characteristics associated in the SEED database with the prokaryotic members of each family, specifically gene clustering and phyletic spread, as well as availability of functional genomics data, and publications that could link candidate families to general metabolic areas, or to specific functions. In-depth comparative genomic analysis was then performed for about 500 top candidate families, which connected ~55 of them to general areas of metabolism and led to specific functional predictions for a subset of ~25 more. Twenty predicted functions were experimentally tested in at least one prokaryotic organism via reverse

  17. Clusterin expression and human testicular seminoma.

    PubMed

    Tang, Min; Li, Jie; Liu, Bianjiang; Song, Ninghong; Wang, Zengjun; Yin, Changjun

    2013-10-01

    Clusterin expression has a positive correlation with the occurrence and progression of various types of tumors from different genetic backgrounds. Clusterin overexpression may protect tumor cells from apoptosis and damage caused by autoimmunity or anti-tumor therapy. Using immunohistochemisty, one previous study showed that clusterin protein expression is downregulated in human testicular seminoma, which is highly sensitive to radiotherapy and chemotherapy. We thus postulate that clusterin expression in human testicular seminoma differs from clusterin expression in other tumors. It may be the cause of the treatable characteristics of testicular seminoma. In the present preliminary study, we detected the abundance of clusterin mRNA in human testicular seminoma and normal testis. The results showed decreased clusterin expression in seminoma at the gene transcription level. Our primary data and summarized previous literature suggest that the downregulation of clusterin expression may be the cause of the high sensitivity of testicular seminoma to radiotherapy and chemotherapy. It may be that the scarcity of clusterin leaves tumor cells with insufficient protection from treatment. This is the first study to focus on the relationship between clusterin expression and human testicular cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Managing for Nature Conservation: from genes to ecosystems

    Treesearch

    Constance I. Millar; Lawrence D. Ford

    1988-01-01

    At many universities nationwide, the new discipline of conservation biology has sparked broad interest. Recently developed courses, like the field of conservation biology itself, have successfully brought together biologists from many disciplines, not just in one classroom, but united by an urgent goal–nature conservation.

  19. Forest gene conservation from the perspective of the international community

    Treesearch

    M. Hosny El-Lakany

    2017-01-01

    conservation of forest genetic resources (FGR). After presenting internationally adopted definitions of some terms related to FGR, the characteristics of the current state of FGR conservation from a global perspective are summarized. Many international and regional organizations and institutions are engaged in the conservation of FGR at degrees ranging from...

  20. Infertility with Testicular Cancer.

    PubMed

    Ostrowski, Kevin A; Walsh, Thomas J

    2015-08-01

    Testicular germ cell cancer is one of the most curable cancers. Most patients are treated during their reproductive years, making infertility a significant quality of life issue after successful treatment. This focused review evaluates the factors that contribute to infertility and specific fertility risks with the various testicular cancer treatments. Timing of patient discussions and current fertility treatments are reviewed.

  1. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP

    PubMed Central

    Escoffier, Jessica; Rahban, Rita; Nef, Serge; Paoloni-Giacobino, Ariane

    2017-01-01

    The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system. PMID:28085963

  2. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP.

    PubMed

    Stenz, Ludwig; Escoffier, Jessica; Rahban, Rita; Nef, Serge; Paoloni-Giacobino, Ariane

    2017-01-01

    The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system.

  3. Conserved gene regulation during acute inflammation between zebrafish and mammals

    PubMed Central

    Forn-Cuní, G.; Varela, M.; Pereiro, P.; Novoa, B.; Figueras, A.

    2017-01-01

    Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress. We provide evidence that immune signaling pathways and single gene expression is well conserved throughout evolution and that the zebrafish and mammal acute genomic responses after lipopolysaccharide stimulation are highly correlated despite the differential susceptibility between species to that compound. Therefore, we formally confirm that zebrafish inflammatory models are suited to study the basic mechanisms of inflammation in human inflammatory diseases, with great translational impact potential. PMID:28157230

  4. Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.

    PubMed

    Boer, Hink; Westerink, Nico-Derk L; Altena, Renske; Nuver, Janine; Dijck-Brouwer, D A Janneke; van Faassen, Martijn; Klont, Frank; Kema, Ido P; Lefrandt, Joop D; Zwart, Nynke; Boezen, H Marike; Smit, Andries J; Meijer, Coby; Gietema, Jourik A

    2016-02-01

    Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors. In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2. The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (<15 nmol/l) and a variant genotype showed a high prevalence of the metabolic syndrome (66.7%). Mean intima-media thickness of the carotid artery and urinary albumin excretion, both markers of vascular damage, were higher in the group of survivors homozygous or heterozygous variant for rs523349 (0.62 versus 0.57 mm, P = 0.026; 5.6 versus 3.1 mg/24 h, P = 0.017, respectively). No association was found between cardiometabolic status and SNP rs9282858 in SRD5A2. Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Isolation of a phylogenetically conserved and testis-specific gene using a monoclonal antibody against the serological H-Y antigen.

    PubMed

    Su, H; Kozak, C A; Veerhuis, R; Lau, Y F; Wiberg, U

    1992-04-01

    Several cDNA clones of a gene termed male-enhanced antigen-2 (Mea-2), have been isolated from a mouse testicular expression cDNA library using a monoclonal histocompatability Y (H-Ys) antibody which detects specific protein(s) present in the mouse testis but not the ovary. The Mea-2 gene is phylogenetically conserved among various mammalian species examined, and is expressed at high levels in adult mouse testis. The expression pattern of Mea-2 is very similar to that of another gene, the male-enhanced antigen-1 (Mea-1), previously isolated using a polyclonal H-Ys antibody. Northern blotting and RT-PCR analyses demonstrated that Mea-2 is also expressed in other adult and fetal mouse organs at low levels. The testis-enhanced expression of this gene is associated with germ cell development at mid- to late-meiotic stages of spermatogenesis. Analysis of an intersubspecies mouse backcross has assigned this gene to chromosome 5, between the loci Gus and Hnf-1.

  6. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    SciTech Connect

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L. . E-mail: leonguo@ha.mc.ntu.edu.tw

    2007-05-15

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.

  7. Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

    PubMed Central

    Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

    2012-01-01

    Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple

  8. Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes.

    PubMed

    Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

    2012-01-01

    Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR-essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR-essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR-essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR-essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR-induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led

  9. Testicular Cancer and Genetics Knowledge Among Familial Testicular Cancer Family Members

    PubMed Central

    Beckjord, Ellen B.; Banda Ryan, Deliya R.; Carr, Ann G.; Vadaparampil, Susan T.; Loud, Jennifer T.; Korde, Larissa; Greene, Mark H.

    2011-01-01

    Purpose It was our aim to determine baseline levels of testicular cancer and genetics knowledge among members of families with Familial Testicular Cancer (FTC). Methods This is a sub-study of an ongoing National Cancer Institute (NCI) multidisciplinary, etiologically-focused, cross-sectional study of FTC. We evaluated 258 male and female participants including testicular cancer (TC) survivors, blood relatives and spouses to assess factors associated with a Genetic Knowledge Scale (GKS) and Testicular Cancer Knowledge Scale (TCKS). Results Knowledge levels were generally low, with genetic knowledge lower than TC knowledge (p<0.01). Men with a personal TC history scored highest on TC knowledge, while gender, age and education differentially influenced knowledge levels, particularly among unaffected relatives. Conclusions Prior to identifying FTC susceptibility genes, we recommend tailoring FTC genetic education to the different informational needs of TC survivors, their spouses and relatives, in preparation for the day when clinical susceptibility testing may be available. PMID:18481162

  10. Conservation of genes and culture: historical and contemporary issues.

    PubMed

    Hodges, J

    2006-02-01

    The paper examines the reasons for and consequences of lost domestic animal biodiversity. The origin of domestic poultry and livestock diversity is reviewed from the first center of domestication in the Middle East during the Neolithic Revolution. Accompanied by domestic animals and birds, mankind spread worldwide over the last 12,000 yr, thereby increasing domestic animal biodiversity via adaptation to many environmental challenges, resulting in about 6,000 breeds within only a small number of species used for food. During the last 50 yr of the 20th century, about 20% of these livestock and poultry breeds have become extinct, and the remainder is at risk. This erosion of unique biodiversity is due to changes in farm practices developed in the West that involve mono-breed, intensive farming systems that are unsustainable. The close symbiotic relationship of Homo sapiens and domestic animals and birds over millennia is changing, resulting in a lost understanding of sustainability among urban communities. The single-minded focus on profit is resulting in the loss of the historic European and Western culture based on Judeo-Christian values. Respect for biological boundaries, community, and quality of life are disappearing in Western society. Concurrently, farming is now only a business. The principal decision makers are no longer farmers but business executives, who are remote from the farm. The emphasis on cheap food is the principal driver that leads to increased competition and unsustainable practices. Farmers as well as their breeds are disappearing. The advent of gene technology and transgenic livestock is reviewed with the prospect of extensive manipulation of animal form and function and abuse of genotypes as animals are redesigned, suffer, and lose all dignity. By handling its animals in this manner, high Western civilization is losing its culture and values and becoming simply the top animal species by using its power selfishly. The case is presented that the

  11. Conservation.

    ERIC Educational Resources Information Center

    National Audubon Society, New York, NY.

    This set of teaching aids consists of seven Audubon Nature Bulletins, providing the teacher and student with informational reading on various topics in conservation. The bulletins have these titles: Plants as Makers of Soil, Water Pollution Control, The Ground Water Table, Conservation--To Keep This Earth Habitable, Our Threatened Air Supply,…

  12. Conservation.

    ERIC Educational Resources Information Center

    National Audubon Society, New York, NY.

    This set of teaching aids consists of seven Audubon Nature Bulletins, providing the teacher and student with informational reading on various topics in conservation. The bulletins have these titles: Plants as Makers of Soil, Water Pollution Control, The Ground Water Table, Conservation--To Keep This Earth Habitable, Our Threatened Air Supply,…

  13. Fluoride exposure changed the structure and the expressions of reproductive related genes in the hypothalamus-pituitary-testicular axis of male mice.

    PubMed

    Han, Haijun; Sun, Zilong; Luo, Guangying; Wang, Chong; Wei, Ruifen; Wang, Jundong

    2015-09-01

    Numerous studies have shown that fluoride exposure adversely affected the male reproductive function, while the molecular mechanism is not clear. The present study was to investigate the effects of fluoride exposure (60 days) on the expressions of reproductive related genes, serum sex hormone levels and structures of the hypothalamus-pituitary-testicular axis (HPTA), which plays a vital role in regulating the spermatogenesis in male mice. In this study, 48 male mice were administrated with 0, 25, 50, and 100 mg/L NaF through drinking water. Results showed that the malformation ratio of sperm was significantly increased (P<0.05). At transcriptional level, the expression levels of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), inhibin alpha (INHα), inhibin beta-B (INHβB), and sex hormone binding globulin (SHBG) mRNA in testis were significantly decreased (P<0.05). Moreover, histological lesions in testis and ultrastructural alterations in hypothalamus, pituitary and testis were obvious. However, the same fluoride exposure did not lead to significant changes of related mRNA expressions in hypothalamus and pituitary (P>0.05). Also, there were no marked changes in serum hormones. Taken together, we conclude that the mechanism of HPTA dysfunction is mainly elucidated through affecting testes, and its effect on hypothalamus and pituitary was secondary at exposure for 60 days.

  14. [Screening of Bacillus thuringiensis strains containing vip3A genes and analysis of gene conservation].

    PubMed

    Chen, Jian-Wu; Tang, Li-Xia; Song, Shao-Yun; Yuan, Mei-Jin; Pang, Yi

    2003-09-01

    Vip3A, a novel insecticidal protein, is secreted by Bacillus thuringiensis (Bt) during vegetative growth. Vip3A protein possesses insecticidal activity against a wild spectrum of lepidopteran insect larvae. Since the first cloning of vip3A gene from Bt, many other vip3A genes have been isolated. To investigate vip3A genes contribution to Bt and reflect the revolution relationships, the strains containing vip3A genes were screened and gene similarity was analyzed. 114 wild-type Bacillus thuringiensis (Bt) strains isolated from different regions and 41 standard Bt strains from the Institute of Pasteur were screened for the vip3A genes using PCR amplification. 39 strains including B. thuringiensis subsp. kurstaki (Btk) HD-1 were found to contain the vip3A genes. Because acrystallerous strain Cry- B derived from Btk HD-1 was proved not to contain vip3A gene, it suppose that the vip3A gene may be located at the plasmids. Vip3A proteins expressed in these strains were detected with polyclonal antibody by Western blot and 4 strains among them were shown not to express the Vip3A proteins. The vip3A genes amplified from wild-type Bacillus thuringiensis strains S101 and 611 with different levels of activity against lepidopteran insect larvae were cloned into pGEM-T Easy vector. Alignment of these 2 putative Vip3A proteins with 6 others (Vip3A (a), Vip3A(b), Vip3A-S, Vip3A-S184, Vip83 and Vip3V) in the GenBank data base and 2 reported Vip3A proteins (Vip14 and Vip15) showed that vip3A genes are highly conservative. The plasmids pOTP-S101 and pOTP-611 were constructed by in- serting 2 vip3A genes (vip3A-S101 and vip3A-611) into the expression vector pQE30 respectively and were transformed into E. coli M15. E. coli M15 cells harboring the pOTP plasmids were induced with 1 mmol/L IPTG to express 89 kDa protein. Experiments showed that the level of soluble proteins of Vip3A-S101 in E. coli M15[pOTP-S101] and Vip3A-611 in E. coli M15 [pOTP-611] were about 48% and 35% respectively

  15. [Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

    PubMed

    Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

    2012-01-01

    Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

  16. Testicular Cancer Resource Center

    MedlinePlus

    ... my what?! Cancer AGAIN?! --- Our comments on the report linking testicular cancer treatments to secondary cancers... Faith and Spirituality --- Not carrying the load alone... Alternative Treatments? --- When all else fails? Spread the Word --- We have even created a, ...

  17. Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

    PubMed

    Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

    2015-11-24

    Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

  18. Identification of a novel gene product, Sertoli cell gene with a zinc finger domain, that is important for FSH activation of testicular Sertoli cells.

    PubMed

    Chaudhary, Jaideep; Skinner, Michael K

    2002-02-01

    Sertoli cells provide the cytoarchitectural support and microenvironment necessary for the process of spermatogenesis. A novel, ubiquitously expressed cDNA clone was isolated from Sertoli cells and termed Sertoli cell gene with a zinc finger domain (SERZ). A significant homology of SERZ was found with a mouse genomic sequence that suggested the presence of at least 10 exons. An open reading frame at the 5'-end of the cDNA, termed SERZ-alpha, had a cryptic basic helix-loop-helix (bHLH) domain, but no start codon. When a start codon was engineered into the 5'-end of the cDNA, an in vitro translation product of SERZ-alpha was obtained. The longest second open reading frame with an ATG start site at 304 bp from the 5'-end coded for a 308-amino acid SERZ-beta polypeptide. Motif analysis and BLAST search of SERZ-beta showed significant homology to the DHHC domain of conserved zinc finger proteins. A number of potential phosphorylation sites were observed in the SERZ-beta polypeptide sequence. The long 5'-untranslated region of SERZ-beta prompted an investigation of both potential alternate polypeptide products, SERZ-alpha and SERZ-beta. Both SERZ-alpha and SERZ-beta proteins were detected with specific antibodies to SERZ-beta and the 5'-end open reading frame SERZ-alpha in a Western blot analysis of total Sertoli cell proteins. The presence of the SERZ-beta polypeptide was also confirmed by in vitro translation of the cDNA, but SERZ-alpha was not translated in vitro in the absence of an engineered start codon. The expression pattern of SERZ mRNA was observed in all tissues examined. The transcript size of SERZ as determined by Northern blot analysis is approximately 2.7 kb. An antisense oligonucleotide to SERZ was found not to influence basal levels of transferrin promoter activation, but significantly blocked FSH-induced transferrin promoter activation. SERZ mRNA expression was not regulated by FSH treatment of Sertoli cell cultures. In summary, a novel gene product

  19. Unusual conservation among genes encoding small secreted salivary gland proteins from a gall midge.

    PubMed

    Chen, Ming-Shun; Liu, Xuming; Yang, Ziheng; Zhao, Huixian; Shukle, Richard H; Stuart, Jeffrey J; Hulbert, Scot

    2010-09-28

    In most protein-coding genes, greater sequence variation is observed in noncoding regions (introns and untranslated regions) than in coding regions due to selective constraints. During characterization of genes and transcripts encoding small secreted salivary gland proteins (SSSGPs) from the Hessian fly, we found exactly the opposite pattern of conservation in several families of genes: the non-coding regions were highly conserved, but the coding regions were highly variable. Seven genes from the SSSGP-1 family are clustered as one inverted and six tandem repeats within a 15 kb region of the genome. Except for SSSGP-1A2, a gene that encodes a protein identical to that encoded by SSSGP-1A1, the other six genes consist of a highly diversified, mature protein-coding region as well as highly conserved regions including the promoter, 5'- and 3'-UTRs, a signal peptide coding region, and an intron. This unusual pattern of highly diversified coding regions coupled with highly conserved regions in the rest of the gene was also observed in several other groups of SSSGP-encoding genes or cDNAs. The unusual conservation pattern was also found in some of the SSSGP cDNAs from the Asian rice gall midge, but not from the orange wheat blossom midge. Strong positive selection was one of the forces driving for diversification whereas concerted homogenization was likely a mechanism for sequence conservation. Rapid diversification in mature SSSGPs suggests that the genes are under selection pressure for functional adaptation. The conservation in the noncoding regions of these genes including introns also suggested potential mechanisms for sequence homogenization that are not yet fully understood. This report should be useful for future studies on genetic mechanisms involved in evolution and functional adaptation of parasite genes.

  20. Structural Relationships between Highly Conserved Elements and Genes in Vertebrate Genomes

    PubMed Central

    Sun, Hong; Skogerbø, Geir; Wang, Zhen; Liu, Wei; Li, Yixue

    2008-01-01

    Large numbers of sequence elements have been identified to be highly conserved among vertebrate genomes. These highly conserved elements (HCEs) are often located in or around genes that are involved in transcription regulation and early development. They have been shown to be involved in cis-regulatory activities through both in vivo and additional computational studies. We have investigated the structural relationships between such elements and genes in six vertebrate genomes human, mouse, rat, chicken, zebrafish and tetraodon and detected several thousand cases of conserved HCE-gene associations, and also cases of HCEs with no common target genes. A few examples underscore the potential significance of our findings about several individual genes. We found that the conserved association between HCE/HCEs and gene/genes are not restricted to elements by their absolute distance on the genome. Notably, long-range associations were identified and the molecular functions of the associated genes do not show any particular overrepresentation of the functional categories previously reported. HCEs in close proximity are found to be linked with different set of gene/genes. The results reflect the highly complex correlation between HCEs and their putative target genes. PMID:19008958

  1. Testicular Microlithiasis: Is It Associated with Testicular Cancer?

    MedlinePlus

    ... diagnosed during a testicular ultrasound — in which small clusters of calcium form in the testicles. A number ... 48:1079. Wang T, et al. A meta-analysis of the relationship between testicular microlithiasis and incidence ...

  2. Testicular Microlithiasis: Is It Associated with Testicular Cancer?

    MedlinePlus

    ... cell tumors (FTGCT) — Overview of a multidisciplinary etiologic study. Andrology. 2015;3:47. Pedersen MR, et al. Testicular microlithiasis and testicular cancer: Review of the literature. International Urology and Nephrology. 2016;48:1079. Wang T, ...

  3. Characterization of Conserved and Non-conserved Imprinted Genes in Swine

    USDA-ARS?s Scientific Manuscript database

    In order to increase our understanding of the role of imprinted genes in swine reproduction we used two complementary approaches, analysis of imprinting by pyrosequencing, and expression profiling of parthenogenetic fetuses, to carry out a comprehensive analysis of this gene family in swine. Using A...

  4. PLIN1 deficiency affects testicular gene expression at the meiotic stage in the first wave of spermatogenesis.

    PubMed

    Chen, Min; Wang, Hong; Li, Xiangdong; Li, Ning; Xu, Guoheng; Meng, Qingyong

    2014-06-15

    PLIN1, a lipid droplet associated protein, has been implicated in playing a key role in the regulation of lipolysis and lipid storage in adipocytes. PLIN1 is found to be highly expressed in Leydig cells of testis, suggesting a potential role in steroidogenesis and spermatogenesis. In this study, we showed that PLIN1 was expressed in testis and that its mRNA levels declined significantly with development. To investigate the role of PLIN1, we take advantage of PLIN1-null mice. We found that the number of seminiferous tubules containing round spermatids was significantly increased at P21 (postnatal day 21). Furthermore, microarray analysis showed that there were 538 differentially expressed genes between PLIN1-null and wild-type mice at P21. The up-regulated genes in knockout mice were enriched in spermatogenesis by Gene Ontology classification. Among them, Prm1 and Wbp2nl are important for spermatogenesis which were confirmed by real-time PCR. Unexpectedly, the levels of serum testosterone and serum 17β-estradiol as well as steroidogenic genes are not altered in the PLIN1-null mice. Compared to the wild-type mice, no significant difference of fertility was found in the PLIN1-null mice. Therefore, these findings indicated that PLIN1 disruption leads to the increase of round spermatid-containing seminiferous tubules at the meiotic stage of the first wave of spermatogenesis through regulating spermatogenic related genes.

  5. Camcore: Thirty-five years of Mesoamerican pine gene conservation

    Treesearch

    J.L. Lopez; W.S. Dvorak; G.R. Hodge

    2017-01-01

    Camcore is an international tree breeding and conservation program with headquarters at North Carolina State University. Camcore was founded in 1980 as a cooperative, non-profit organization to identify and save the dwindling natural populations of pines in the highland regions of Guatemala in Central America. Funded by the private sector, the program has played an...

  6. From genes to landscapes: conserving biodiversity at multiple scales.

    Treesearch

    Sally. Duncan

    2000-01-01

    Biodiversity has at last become a familiar term outside of scientific circles. Ways of measuring it and mapping it are advancing and becoming more complex, but ways of deciding how to conserve it remain mixed at best, and the resources available to manage dimishing biodiversity are themselves scarce. One significant problem is that policy decisions are frequently at...

  7. Teaching about Testicular Cancer and Testicular Self-examination.

    ERIC Educational Resources Information Center

    Marty, Phillip J.; McDermott, Robert J.

    1983-01-01

    Because testicular cancer is one of the most commonly diagnosed cancers in young men, it is important that they become informed about it. This paper reviews the pathology and epidemiology of testicular cancer, the technique of testicular self-examination, and some suggestions for teaching about this subject. (Authors/JMK)

  8. Testicular calculus: A rare case.

    PubMed

    Sen, Volkan; Bozkurt, Ozan; Demır, Omer; Tuna, Burcin; Yorukoglu, Kutsal; Esen, Adil

    2015-01-01

    Testicular calculus is an extremely rare case with unknown etiology and pathogenesis. To our knowledge, here we report the third case of testicular calculus. A 31-year-old man was admitted to our clinic with painful solid mass in left testis. After diagnostic work-up for a possible testicular tumour, he underwent inguinal orchiectomy and histopathologic examination showed a testicular calculus. Case hypothesis: Solid testicular lesions in young adults generally correspond to testicular cancer. Differential diagnosis should be done carefully. Future implications: In young adults with painful and solid testicular mass with hyperechogenic appearance on scrotal ultrasonography, testicular calculus must be kept in mind in differential diagnosis. Further reports on this topic may let us do more clear recommendations about the etiology and treatment of this rare disease.

  9. Sorting out inherent features of head-to-head gene pairs by evolutionary conservation

    PubMed Central

    2010-01-01

    Background A ‘head-to-head’ (h2h) gene pair is defined as a genomic locus in which two adjacent genes are divergently transcribed from opposite strands of DNA. In our previous work, this gene organization was found to be ancient and conserved, which subjects functionally related genes to transcriptional co-regulation. However, some of the biological features of h2h pairs still need further clarification. Results In this work, we assorted human h2h pairs into four sequentially inclusive sets of gradually incremental conservation, and examined whether those previously asserted features were conserved or sharpened in the more conserved h2h pair sets in order to identify the inherent features of the h2h gene organization. The features of TSS distance, expression correlation within h2h pairs and among h2h genes, transcription factor association and functional similarities of h2h genes were examined. Our conservation-based analyses found that the bi-directional promoters of h2h gene pairs are most likely shorter than 100 bp; h2h gene pairs generally have only significant positive expression correlation but not negative correlation, and remarkably high positive expression correlations exist among h2h genes, as well as between h2h pairs observed in our previous study; h2h paired genes tend to share transcription factors. In addition, expression correlation of h2h pairs is positively related with the TF-sharing and functional coordination, while not related with TSS distance. Conclusions Our findings remove the uncertainties of h2h genes about TSS distance, expression correlation and functional coordination, which provide insights into the study on the molecular mechanisms and functional consequences of the transcriptional regulation based on this special gene organization. PMID:21172051

  10. The effects of chemotherapy with bleomycin, etoposide, and cis-platinum (BEP) on rat sperm chromatin remodeling, fecundity and testicular gene expression in the progeny.

    PubMed

    Maselli, Jennifer; Hales, Barbara F; Robaire, Bernard

    2013-10-01

    During spermiogenesis, histones are replaced first by transition proteins and then by protamines, resulting in a very condensed sperm DNA structure that is absolutely critical for normal sperm function. We have demonstrated previously that, despite a 9-wk recovery period, mature sperm from rats treated for 9 wk with bleomycin, etoposide, and cis-platinum (BEP), the drugs used to treat testicular cancer, have reduced levels of protamine 1 and a concomitant upregulation of specific histones, highlighting a problem in histone eviction. Here, we demonstrate that regulators of histone removal are increased in elongating spermatids following recovery; however, Ac-H4 and gamma H2AX histones remain elevated in elongating spermatids or caudal epididymal spermatozoa 9 wk post-BEP treatment. This indicates that chromatin remodelers and effector proteins that respond to histone removal cues may be a target of BEP treatment. A decrease in the expression of SMARCE1 in elongating spermatids may explain the persistent retention of histones in cauda epididymal sperm 9 wk after the cessation of BEP treatment. Remarkably, proteins implicated in the translational control and posttranslational processing of protamine 1 are also significantly elevated 9 wk post-BEP treatment, suggesting that histone eviction may dictate the DNA availability for protamine binding. Males mated to control females 9 wk after BEP treatment have reduced litter sizes; moreover, the profile of gene expression in the developing testes of their pups is altered. Altering the proportion of histones to protamine in mature spermatozoa has an adverse impact on male fecundity, with modifications to epigenetic marks potentially threatening normal progeny development.

  11. Conserved nodulation genes in Rhizobium meliloti and Rhizobium trifolii

    SciTech Connect

    Fisher, R.F.; Tu, J.K.; Long, S.R.

    1985-06-01

    Plasmids which contained wild-type or mutated Rhizobium meliloti nodulation (Nod) genes were introduced into Nod/sup -/ R. trifolii mutants ANU453 and ANU851 and tested for their ability to nodulate clover. Cloned wild-type and mutated R. meliloti Nod gene segments restored ANU851 to Nod/sup +/, with the exception of nodD mutants. Similarly, wild-type and mutant R. meliloti nod genes complemented ANU453 to Nod/sup +/, except for nod CII mutants. Thus, ANU851 identifies the equivalent of the R. meliloti nodD genes, and ANU453 specifies the equivalent of the R. meliloti nodCII genes. In addition, cloned wild-type R. trifolii nod genes were introduced into seven R. meliloti Nod/sup -/ mutants. All seven mutants were restored to Nod/sup +/ on alfalfa. Our results indicate that these genes represent common nodulation functions and argue for an allelic relationship between nod genes in R. meliloti and R. trifolii.

  12. Evolutionary conservation of the eumetazoan gene regulatory landscape

    PubMed Central

    Schwaiger, Michaela; Schönauer, Anna; Rendeiro, André F.; Pribitzer, Carina; Schauer, Alexandra; Gilles, Anna F.; Schinko, Johannes B.; Renfer, Eduard; Fredman, David; Technau, Ulrich

    2014-01-01

    Despite considerable differences in morphology and complexity of body plans among animals, a great part of the gene set is shared among Bilateria and their basally branching sister group, the Cnidaria. This suggests that the common ancestor of eumetazoans already had a highly complex gene repertoire. At present it is therefore unclear how morphological diversification is encoded in the genome. Here we address the possibility that differences in gene regulation could contribute to the large morphological divergence between cnidarians and bilaterians. To this end, we generated the first genome-wide map of gene regulatory elements in a nonbilaterian animal, the sea anemone Nematostella vectensis. Using chromatin immunoprecipitation followed by deep sequencing of five chromatin modifications and a transcriptional cofactor, we identified over 5000 enhancers in the Nematostella genome and could validate 75% of the tested enhancers in vivo. We found that in Nematostella, but not in yeast, enhancers are characterized by the same combination of histone modifications as in bilaterians, and these enhancers preferentially target developmental regulatory genes. Surprisingly, the distribution and abundance of gene regulatory elements relative to these genes are shared between Nematostella and bilaterian model organisms. Our results suggest that complex gene regulation originated at least 600 million yr ago, predating the common ancestor of eumetazoans. PMID:24642862

  13. An atlas of tissue-specific conserved coexpression for functional annotation and disease gene prediction.

    PubMed

    Piro, Rosario Michael; Ala, Ugo; Molineris, Ivan; Grassi, Elena; Bracco, Chiara; Perego, Gian Paolo; Provero, Paolo; Di Cunto, Ferdinando

    2011-11-01

    Gene coexpression relationships that are phylogenetically conserved between human and mouse have been shown to provide important clues about gene function that can be efficiently used to identify promising candidate genes for human hereditary disorders. In the past, such approaches have considered mostly generic gene expression profiles that cover multiple tissues and organs. The individual genes of multicellular organisms, however, can participate in different transcriptional programs, operating at scales as different as single-cell types, tissues, organs, body regions or the entire organism. Therefore, systematic analysis of tissue-specific coexpression could be, in principle, a very powerful strategy to dissect those functional relationships among genes that emerge only in particular tissues or organs. In this report, we show that, in fact, conserved coexpression as determined from tissue-specific and condition-specific data sets can predict many functional relationships that are not detected by analyzing heterogeneous microarray data sets. More importantly, we find that, when combined with disease networks, the simultaneous use of both generic (multi-tissue) and tissue-specific conserved coexpression allows a more efficient prediction of human disease genes than the use of generic conserved coexpression alone. Using this strategy, we were able to identify high-probability candidates for 238 orphan disease loci. We provide proof of concept that this combined use of generic and tissue-specific conserved coexpression can be very useful to prioritize the mutational candidates obtained from deep-sequencing projects, even in the case of genetic disorders as heterogeneous as XLMR.

  14. Treatment Options for Testicular Cancer, by Type and Stage

    MedlinePlus

    ... Treating Testicular Cancer Surgery for Testicular Cancer Radiation Therapy for Testicular Cancer Chemotherapy for Testicular Cancer High-Dose Chemotherapy ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  15. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees.

    PubMed

    Liu, Hui; Robinson, Gene E; Jakobsson, Eric

    2016-06-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization.

  16. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees

    PubMed Central

    Robinson, Gene E.; Jakobsson, Eric

    2016-01-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization

  17. Sexually dimorphic gene expressions in eels: useful markers for early sex assessment in a conservation context

    NASA Astrophysics Data System (ADS)

    Geffroy, Benjamin; Guilbaud, Florian; Amilhat, Elsa; Beaulaton, Laurent; Vignon, Matthias; Huchet, Emmanuel; Rives, Jacques; Bobe, Julien; Fostier, Alexis; Guiguen, Yann; Bardonnet, Agnès

    2016-09-01

    Environmental sex determination (ESD) has been detected in a range of vertebrate reptile and fish species. Eels are characterized by an ESD that occurs relatively late, since sex cannot be histologically determined before individuals reach 28 cm. Because several eel species are at risk of extinction, assessing sex at the earliest stage is a crucial management issue. Based on preliminary results of RNA sequencing, we targeted genes susceptible to be differentially expressed between ovaries and testis at different stages of development. Using qPCR, we detected testis-specific expressions of dmrt1, amh, gsdf and pre-miR202 and ovary-specific expressions were obtained for zar1, zp3 and foxn5. We showed that gene expressions in the gonad of intersexual eels were quite similar to those of males, supporting the idea that intersexual eels represent a transitional stage towards testicular differentiation. To assess whether these genes would be effective early molecular markers, we sampled juvenile eels in two locations with highly skewed sex ratios. The combined expression of six of these genes allowed the discrimination of groups according to their potential future sex and thus this appears to be a useful tool to estimate sex ratios of undifferentiated juvenile eels.

  18. Sexually dimorphic gene expressions in eels: useful markers for early sex assessment in a conservation context

    PubMed Central

    Geffroy, Benjamin; Guilbaud, Florian; Amilhat, Elsa; Beaulaton, Laurent; Vignon, Matthias; Huchet, Emmanuel; Rives, Jacques; Bobe, Julien; Fostier, Alexis; Guiguen, Yann; Bardonnet, Agnès

    2016-01-01

    Environmental sex determination (ESD) has been detected in a range of vertebrate reptile and fish species. Eels are characterized by an ESD that occurs relatively late, since sex cannot be histologically determined before individuals reach 28 cm. Because several eel species are at risk of extinction, assessing sex at the earliest stage is a crucial management issue. Based on preliminary results of RNA sequencing, we targeted genes susceptible to be differentially expressed between ovaries and testis at different stages of development. Using qPCR, we detected testis-specific expressions of dmrt1, amh, gsdf and pre-miR202 and ovary-specific expressions were obtained for zar1, zp3 and foxn5. We showed that gene expressions in the gonad of intersexual eels were quite similar to those of males, supporting the idea that intersexual eels represent a transitional stage towards testicular differentiation. To assess whether these genes would be effective early molecular markers, we sampled juvenile eels in two locations with highly skewed sex ratios. The combined expression of six of these genes allowed the discrimination of groups according to their potential future sex and thus this appears to be a useful tool to estimate sex ratios of undifferentiated juvenile eels. PMID:27658729

  19. Conservation of Transcription Start Sites within Genes across a Bacterial Genus

    SciTech Connect

    Shao, Wenjun; Price, Morgan N.; Deutschbauer, Adam M.; Romine, Margaret F.; Arkin, Adam P.

    2014-07-01

    Transcription start sites (TSSs) lying inside annotated genes, on the same or opposite strand, have been observed in diverse bacteria, but the function of these unexpected transcripts is unclear. Here, we use the metal-reducing bacterium Shewanella oneidensis MR-1 and its relatives to study the evolutionary conservation of unexpected TSSs. Using high-resolution tiling microarrays and 5'-end RNA sequencing, we identified 2,531 TSSs in S. oneidensis MR-1, of which 18% were located inside coding sequences (CDSs). Comparative transcriptome analysis with seven additional Shewanella species revealed that the majority (76%) of the TSSs within the upstream regions of annotated genes (gTSSs) were conserved. Thirty percent of the TSSs that were inside genes and on the sense strand (iTSSs) were also conserved. Sequence analysis around these iTSSs showed conserved promoter motifs, suggesting that many iTSS are under purifying selection. Furthermore, conserved iTSSs are enriched for regulatory motifs, suggesting that they are regulated, and they tend to eliminate polar effects, which confirms that they are functional. In contrast, the transcription of antisense TSSs located inside CDSs (aTSSs) was significantly less likely to be conserved (22%). However, aTSSs whose transcription was conserved often have conserved promoter motifs and drive the expression of nearby genes. Overall, our findings demonstrate that some internal TSSs are conserved and drive protein expression despite their unusual locations, but the majority are not conserved and may reflect noisy initiation of transcription rather than a biological function.

  20. Sense-antisense gene pairs: sequence, transcription, and structure are not conserved between human and mouse

    PubMed Central

    Wood, Emily J.; Chin-Inmanu, Kwanrutai; Jia, Hui; Lipovich, Leonard

    2013-01-01

    Previous efforts to characterize conservation between the human and mouse genomes focused largely on sequence comparisons. These studies are inherently limited because they don't account for gene structure differences, which may exist despite genomic sequence conservation. Recent high-throughput transcriptome studies have revealed widespread and extensive overlaps between genes, and transcripts, encoded on both strands of the genomic sequence. This overlapping gene organization, which produces sense-antisense (SAS) gene pairs, is capable of effecting regulatory cascades through established mechanisms. We present an evolutionary conservation assessment of SAS pairs, on three levels: genomic, transcriptomic, and structural. From a genome-wide dataset of human SAS pairs, we first identified orthologous loci in the mouse genome, then assessed their transcription in the mouse, and finally compared the genomic structures of SAS pairs expressed in both species. We found that approximately half of human SAS loci have single orthologous locations in the mouse genome; however, only half of those orthologous locations have SAS transcriptional activity in the mouse. This suggests that high human-mouse gene conservation overlooks widespread distinctions in SAS pair incidence and expression. We compared gene structures at orthologous SAS loci, finding frequent differences in gene structure between human and orthologous mouse SAS pair members. Our categorization of human SAS pairs with respect to mouse conservation of expression as well as structure points to limitations of mouse models. Gene structure differences, including at SAS loci, may account for some of the phenotypic distinctions between primates and rodents. Genes in non-conserved SAS pairs may contribute to evolutionary lineage-specific regulatory outcomes. PMID:24133500

  1. Unconventional conservation among genes encoding small secreted salivary sland proteins from a gall midge

    USDA-ARS?s Scientific Manuscript database

    Due to functional constraints associated with protein-coding sequences, introns and the 3’-untranslated region (UTR) of most genes vary the most, followed by the 5’-UTR. The coding region is the most conserved due to stronger functional constraints. During characterization of transcripts and gene...

  2. Conserving plants in gene banks and nature: Investigating complementarity with Trifolium thompsonii Morton

    USDA-ARS?s Scientific Manuscript database

    A standard conservation strategy for plant genetic resources integrates in situ (on-farm or wild) and ex situ (gene or field bank) approaches. Gene bank managers collect ex situ accessions that represent a comprehensive snap shot of the genetic diversity of in situ populations at a given time and pl...

  3. Conservation of Arabidopsis thaliana circadian clock genes in Chrysanthemum lavandulifolium.

    PubMed

    Fu, Jianxin; Yang, Liwen; Dai, Silan

    2014-07-01

    In Arabidopsis, circadian clock genes play important roles in photoperiod pathway by regulating the daytime expression of CONSTANS (CO), but related reports for chrysanthemum are notably limited. In this study, we isolated eleven circadian clock genes, which lie in the three interconnected negative and positive feedback loops in a wild diploid chrysanthemum, Chrysanthemum lavandulifolium. With the exception of ClELF3, ClPRR1 and ClPRR73, most of the circadian clock genes are expressed more highly in leaves than in other tested tissues. The diurnal rhythms of these circadian clock genes are similar to those of their homologs in Arabidopsis. ClELF3 and ClZTL are constitutively expressed at all time points in both assessed photoperiods. The expression succession from morning to night of the PSEUDO RESPONSE REGULATOR (PRR) gene family occurs in the order ClPRR73/ClPRR37, ClPRR5, and then ClPRR1. ClLHY is expressed during the dawn period, and ClGIs is expressed during the dusk period. The peak expression levels of ClFKF1 and ClGIs are synchronous in the inductive photoperiod. However, in the non-inductive night break (NB) condition or non-24 h photoperiod, the peak expression level of ClFKF1 is significantly changed, indicating that ClFKF1 itself or the synchronous expression of ClFKF1 and ClGIs might be essential to initiate the flowering of C. lavandulifolium. This study provides the first extensive evaluation of circadian clock genes, and it presents a useful foundation for dissecting the functions of circadian clock genes in C. lavandulifolium. Copyright © 2014. Published by Elsevier Masson SAS.

  4. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

    PubMed Central

    2010-01-01

    Background Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. Results We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. Conclusion The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes. PMID:21172044

  5. Spin on perinatal testicular torsion.

    PubMed

    Samnakay, Naeem; Tudehope, David; Walker, Rosslyn

    2006-11-01

    We describe a recent case of perinatal testicular torsion at our institution. The presentation, management and outcome of perinatal testicular torsion are quite different to testicular torsion in the general paediatric population. The literature describes a variety of management options for perinatal testicular torsion and these are briefly reviewed. In cases of unilateral perinatal testicular torsin, there is controversy over whether surgery to fix the contralateral testis is required, and if so, the appropriate timing for the surgery. A good understanding of the issues unique to perinatal torsion will facilitate appropriate counseling of parents of affected neonates.

  6. Conservation of floral homeotic gene function between Arabidopsis and antirrhinum.

    PubMed Central

    Irish, V F; Yamamoto, Y T

    1995-01-01

    Several homeotic genes controlling floral development have been isolated in both Antirrhinum and Arabidopsis. Based on the similarities in sequence and in the phenotypes elicited by mutations in some of these genes, it has been proposed that the regulatory hierarchy controlling floral development is comparable in these two species. We have performed a direct experimental test of this hypothesis by introducing a chimeric Antirrhinum Deficiens (DefA)/Arabidopsis APETALA3 (AP3) gene, under the control of the Arabidopsis AP3 promoter, into Arabidopsis. We demonstrated that this transgene is sufficient to partially complement severe mutations at the AP3 locus. In combination with a weak ap3 mutation, this transgene is capable of completely rescuing the mutant phenotype to a fully functional wild-type flower. These observations indicate that despite differences in DNA sequence and expression, DefA coding sequences can compensate for the loss of AP3 gene function. We discuss the implications of these results for the evolution of homeotic gene function in flowering plants. PMID:7580255

  7. Testicular cancer and male infertility.

    PubMed

    Paduch, Darius A

    2006-11-01

    Testicular cancer and infertility affect a similar age group of patients and have common biologic, epidemiologic, and environmental backgrounds. In this review, we provide current literature on links between infertility and testicular cancer, and new developments in the management of testicular cancer aimed at improving quality of life in men with testicular cancer. In-utero environmental exposure to endocrine disruptors modulates the genetically determined fate of primitive gonad and results in testicular dysgenesis syndrome, which may result in infertility and testicular cancer. Excellent response of testicular cancer to radiation and chemotherapy results in over 90% of survival and quality of life--fertility and sexual function--is of significant concern to patients and clinicians. The testicular-sparing management of testicular masses emerges as a sound alternative to radical orchiectomy and allows for preservation of spermatogenesis and hormonal function, and at the same time achieving similar survival rates. Secondary malignancies, pulmonary, and cardiovascular complications are recognized as late complications of treatment for testicular cancer. Better understanding of common mechanisms involved in infertility and testicular cancer, and scientifically driven evidence-based treatment options should improve quality of life in young men faced with this potentially life-threatening disease.

  8. Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth.

    PubMed

    Chaillou, Thomas; Jackson, Janna R; England, Jonathan H; Kirby, Tyler J; Richards-White, Jena; Esser, Karyn A; Dupont-Versteegden, Esther E; McCarthy, John J

    2015-01-01

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. Copyright © 2015 the American Physiological Society.

  9. Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth

    PubMed Central

    Chaillou, Thomas; Jackson, Janna R.; England, Jonathan H.; Kirby, Tyler J.; Richards-White, Jena; Esser, Karyn A.; Dupont-Versteegden, Esther E.

    2014-01-01

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. PMID:25554798

  10. Conservation of the structure and organization of lupin mitochondrial nad3 and rps12 genes.

    PubMed

    Rurek, M; Oczkowski, M; Augustyniak, H

    1998-01-01

    A high level of the nucleotide sequence conservation of mitochondrial nad3 and rps12 genes was found in four lupin species. The only differences concern three nucleotides in the Lupinus albus rps12 gene and three nucleotides insertion in the L. mutabilis spacer. Northern blot analysis as well as RT-PCR confirmed cotranscription of the L. luteus genes because the transcripts detected were long enough.

  11. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates

    PubMed Central

    Kikuta, Hiroshi; Laplante, Mary; Navratilova, Pavla; Komisarczuk, Anna Z.; Engström, Pär G.; Fredman, David; Akalin, Altuna; Caccamo, Mario; Sealy, Ian; Howe, Kerstin; Ghislain, Julien; Pezeron, Guillaume; Mourrain, Philippe; Ellingsen, Staale; Oates, Andrew C.; Thisse, Christine; Thisse, Bernard; Foucher, Isabelle; Adolf, Birgit; Geling, Andrea; Lenhard, Boris; Becker, Thomas S.

    2007-01-01

    We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated “bystander” genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs. PMID:17387144

  12. Human U1 small nuclear RNA genes: extensive conservation of flanking sequences suggests cycles of gene amplification and transposition.

    PubMed Central

    Bernstein, L B; Manser, T; Weiner, A M

    1985-01-01

    The DNA immediately flanking the 164-base-pair U1 RNA coding region is highly conserved among the approximately 30 human U1 genes. The U1 multigene family also contains many U1 pseudogenes (designated class I) with striking although imperfect flanking homology to the true U1 genes. Using cosmid vectors, we now have cloned, characterized, and partially sequenced three 35-kilobase (kb) regions of the human genome spanning U1 homologies. Two clones contain one true U1 gene each, and the third bears two class I pseudogenes 9 kb apart in the opposite orientation. We show by genomic blotting and by direct DNA sequence determination that the conserved sequences surrounding U1 genes are much more extensive than previously estimated: nearly perfect sequence homology between many true U1 genes extends for at least 24 kb upstream and at least 20 kb downstream from the U1 coding region. In addition, the sequences of the two new pseudogenes provide evidence that class I U1 pseudogenes are more closely related to each other than to true genes. Finally, it is demonstrated elsewhere (Lindgren et al., Mol. Cell. Biol. 5:2190-2196, 1985) that both true U1 genes and class I U1 pseudogenes map to chromosome 1, but in separate clusters located far apart on opposite sides of the centromere. Taken together, these results suggest a model for the evolution of the U1 multigene family. We speculate that the contemporary family of true U1 genes was derived from a more ancient family of U1 genes (now class I U1 pseudogenes) by gene amplification and transposition. Gene amplification provides the simplest explanation for the clustering of both U1 genes and class I pseudogenes and for the conservation of at least 44 kb of DNA flanking the U1 coding region in a large fraction of the 30 true U1 genes. Images PMID:3837185

  13. Characterization of Conserved and Nonconserved Imprinted Genes in Swine

    USDA-ARS?s Scientific Manuscript database

    Genomic imprinting results in the silencing of a subset of mammalian alleles due to parent-of-origin inheritance. Due to the nature of their expression patterns they play a critical role in placental and early embryonic development. In order to increase our understanding of imprinted genes specifi...

  14. Conserved deployment of genes during odontogenesis across osteichthyans.

    PubMed

    Fraser, Gareth J; Graham, Anthony; Smith, Moya M

    2004-11-22

    Odontogenesis has only been closely scrutinized at the molecular level in the mouse, an animal with an extremely restricted dentition of only two types and one set. However, within osteichthyans many species display complex and extensive dentitions, which questions the extent to which information from the mouse is applicable to all osteichthyans. We present novel comparative molecular and morphological data in the rainbow trout (Oncorhynchus mykiss) that show that three genes, essential for murine odontogenesis, follow identical spatial-temporal expression. Thus, at all tooth bud sites, epithelial genes Pitx-2 and Shh initiate the odontogenic cascade, resulting in dental mesenchymal Bmp-4 expression, importantly, including the previously unknown formation of replacement teeth. Significantly, this spatial-temporal sequence is the same for marginal and lingual dentitions, but we find notable differences regarding the deployment of Pitx-2 in the developing pharyngeal dentition. This difference may be highly significant in relation to the theory that dentitions may have evolved from pharyngeal tooth sets in jawless fishes. We have provided the first data on operational genes in tooth development to show that the same signalling genes choreograph this evolutionary stable event in fishes since the osteichthyan divergence 420 Myr ago, with the identical spatial-temporal expression as in mammals.

  15. Conserved deployment of genes during odontogenesis across osteichthyans.

    PubMed Central

    Fraser, Gareth J.; Graham, Anthony; Smith, Moya M.

    2004-01-01

    Odontogenesis has only been closely scrutinized at the molecular level in the mouse, an animal with an extremely restricted dentition of only two types and one set. However, within osteichthyans many species display complex and extensive dentitions, which questions the extent to which information from the mouse is applicable to all osteichthyans. We present novel comparative molecular and morphological data in the rainbow trout (Oncorhynchus mykiss) that show that three genes, essential for murine odontogenesis, follow identical spatial-temporal expression. Thus, at all tooth bud sites, epithelial genes Pitx-2 and Shh initiate the odontogenic cascade, resulting in dental mesenchymal Bmp-4 expression, importantly, including the previously unknown formation of replacement teeth. Significantly, this spatial-temporal sequence is the same for marginal and lingual dentitions, but we find notable differences regarding the deployment of Pitx-2 in the developing pharyngeal dentition. This difference may be highly significant in relation to the theory that dentitions may have evolved from pharyngeal tooth sets in jawless fishes. We have provided the first data on operational genes in tooth development to show that the same signalling genes choreograph this evolutionary stable event in fishes since the osteichthyan divergence 420 Myr ago, with the identical spatial-temporal expression as in mammals. PMID:15556883

  16. Identification of essential Alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems

    PubMed Central

    Curtis, Patrick D.; Brun, Yves V.

    2014-01-01

    Summary The cell cycle of Caulobacter crescentus is controlled by a complex signaling network that coordinates events. Genome sequencing has revealed many C. crescentus cell cycle genes are conserved in other Alphaproteobacteria, but it is not clear to what extent their function is conserved. As many cell cycle regulatory genes are essential in C. crescentus, the essential genes of two Alphaproteobacteria, Agrobacterium tumefaciens (Rhizobiales) and Brevundimonas subvibrioides (Caulobacterales), were elucidated to identify changes in cell cycle protein function over different phylogenetic distances as demonstrated by changes in essentiality. The results show the majority of conserved essential genes are involved in critical cell cycle processes. Changes in component essentiality reflect major changes in lifestyle, such as divisome components in A. tumefaciens resulting from that organism’s different growth pattern. Larger variability of essentiality was observed in cell cycle regulators, suggesting regulatory mechanisms are more customizable than the processes they regulate. Examples include variability in the essentiality of divJ and divK spatial cell cycle regulators, and non-essentiality of the highly conserved and usually essential DNA methyltransferase CcrM. These results show that while essential cell functions are conserved across varying genetic distance, much of a given organism’s essential gene pool is specific to that organism. PMID:24975755

  17. Functional conservation of MIKC*-Type MADS box genes in Arabidopsis and rice pollen maturation.

    PubMed

    Liu, Yuan; Cui, Shaojie; Wu, Feng; Yan, Shuo; Lin, Xuelei; Du, Xiaoqiu; Chong, Kang; Schilling, Susanne; Theißen, Günter; Meng, Zheng

    2013-04-01

    There are two groups of MADS intervening keratin-like and C-terminal (MIKC)-type MADS box genes, MIKC(C) type and MIKC* type. In seed plants, the MIKC(C) type shows considerable diversity, but the MIKC* type has only two subgroups, P- and S-clade, which show conserved expression in the gametophyte. To examine the functional conservation of MIKC*-type genes, we characterized all three rice (Oryza sativa) MIKC*-type genes. All three genes are specifically expressed late in pollen development. The single knockdown or knockout lines, respectively, of the S-clade MADS62 and MADS63 did not show a mutant phenotype, but lines in which both S-clade genes were affected showed severe defects in pollen maturation and germination, as did knockdown lines of MADS68, the only P-clade gene in rice. The rice MIKC*-type proteins form strong heterodimeric complexes solely with partners from the other subclade; these complexes specifically bind to N10-type C-A-rich-G-boxes in vitro and regulate downstream gene expression by binding to N10-type promoter motifs. The rice MIKC* genes have a much lower degree of functional redundancy than the Arabidopsis thaliana MIKC* genes. Nevertheless, our data indicate that the function of heterodimeric MIKC*-type protein complexes in pollen development has been conserved since the divergence of monocots and eudicots, roughly 150 million years ago.

  18. Gene body methylation is conserved between plant orthologs and is of evolutionary consequence

    PubMed Central

    Takuno, Shohei; Gaut, Brandon S.

    2013-01-01

    DNA methylation is a common feature of eukaryotic genomes and is especially common in noncoding regions of plants. Protein coding regions of plants are often methylated also, but the extent, function, and evolutionary consequences of gene body methylation remain unclear. Here we investigate gene body methylation using an explicit comparative evolutionary approach. We generated bisulfite sequencing data from two tissues of Brachypodium distachyon and compared genic methylation patterns to those of rice (Oryza sativa ssp. japonica). Gene body methylation was strongly conserved between orthologs of the two species and affected a biased subset of long, slowly evolving genes. Because gene body methylation is conserved over evolutionary time, it shapes important features of plant genome evolution, such as the bimodality of G+C content among grass genes. Our results superficially contradict previous observations of high cytosine methylation polymorphism within Arabidopsis thaliana genes, but reanalyses of these data are consistent with conservation of methylation within gene regions. Overall, our results indicate that the methylation level is a long-term property of individual genes and therefore of evolutionary consequence. PMID:23319627

  19. Testicular Cancer and Cryptorchidism

    PubMed Central

    Ferguson, Lydia; Agoulnik, Alexander I.

    2013-01-01

    The failure of testicular descent or cryptorchidism is the most common defect in newborn boys. The descent of the testes during development is controlled by insulin-like 3 peptide and steroid hormones produced in testicular Leydig cells, as well as by various genetic and developmental factors. While in some cases the association with genetic abnormalities and environmental causes has been shown, the etiology of cryptorchidism remains uncertain. Cryptorchidism is an established risk factor for infertility and testicular germ cell tumors (TGCT). Experimental animal models suggest a causative role for an abnormal testicular position on the disruption of spermatogenesis however the link between cryptorchidism and TGCT is less clear. The most common type of TGCT in cryptorchid testes is seminoma, believed to be derived from pluripotent prenatal germ cells. Recent studies have shown that seminoma cells and their precursor carcinoma in situ cells express a number of spermatogonial stem cell (SSC) markers suggesting that TGCTs might originate from adult stem cells. We review here the data on changes in the SSC somatic cell niche observed in cryptorchid testes of mouse models and in human patients. We propose that the misregulation of growth factors’ expression may alter the balance between SSC self-renewal and differentiation and shift stem cells toward neoplastic transformation. PMID:23519268

  20. Primary testicular lymphoma.

    PubMed

    Ahmad, S S; Idris, S F; Follows, G A; Williams, M V

    2012-06-01

    Primary testicular non-Hodgkin lymphoma (PTL) comprises around 9% of testicular cancers and 1-2% of all non-Hodgkin lymphomas. Its incidence is increasing and it primarily affects older men, with a median age at presentation of around 67 years. By far the most common histological subtype is diffuse large B-cell lymphoma, accounting for 80-90% of PTLs. Most patients present with a unilateral testicular mass or swelling. Up to 90% of patients have stage I or II disease at diagnosis (60 and 30%, respectively) and bilateral testicular involvement is seen in around 35% of patients. PTL demonstrates a continuous pattern of relapse and propensity for extra-nodal sites such as the central nervous system and contralateral testis. Retrospective data have emphasised the importance of prophylactic radiotherapy in reducing recurrence rates within the contralateral testis. Recent outcome data from the prospective IELSG-10 trial have shown far better progression-free and overall survival than historical outcomes. This supports the use of orchidectomy followed by Rituximab- cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), central nervous system prophylaxis and prophylactic radiotherapy to the contralateral testis with or without nodal radiotherapy in patients with limited disease. Central nervous system relapse remains a significant issue and future research should focus on identifying the best strategy to reduce its occurrence. Here we discuss the evidence supporting combination chemotherapy and radiotherapy in PTL.

  1. Conservation of the pyrrolnitrin biosynthetic gene cluster among six pyrrolnitrin-producing strains.

    PubMed

    Hammer, P E; Burd, W; Hill, D S; Ligon, J M; van Pée, K

    1999-11-01

    The prnABCD gene cluster from Pseudomonas fluorescens encodes the biosynthetic pathway for pyrrolnitrin, a secondary metabolite derived from tryptophan which has strong anti-fungal activity. We used the prn genes from P. fluorescens strain BL915 as a probe to clone and sequence homologous genes from three other Pseudomonas strains, Burkholderia cepacia and Myxococcus fulvus. With the exception of the prnA gene from M. fulvus59% similar among the strains, indicating that the biochemical pathway for pyrrolnitrin biosynthesis is highly conserved. The prnA gene from M. fulvus is about 45% similar to prnA from the other strains and contains regions which are highly conserved among all six strains.

  2. An Intact Retroviral Gene Conserved in Spiny-Rayed Fishes for over 100 My.

    PubMed

    Henzy, Jamie E; Gifford, Robert J; Kenaley, Christopher P; Johnson, Welkin E

    2016-12-30

    We have identified a retroviral envelope gene with a complete, intact open reading frame (ORF) in 20 species of spiny-rayed fishes (Acanthomorpha). The taxonomic distribution of the gene, "percomORF", indicates insertion into the ancestral lineage >110 Ma, making it the oldest known conserved gene of viral origin in a vertebrate genome. Underscoring its ancient provenence, percomORF exists as an isolated ORF within the intron of a widely conserved host gene, with no discernible proviral sequence nearby. Despite its remarkable age, percomORF retains canonical features of a retroviral glycoprotein, and tests for selection strongly suggest cooption for a host function. Retroviral envelope genes have been coopted for a role in placentogenesis by numerous lineages of mammals, including eutherians and marsupials, representing a variety of placental structures. Therefore percomORF's presence within the group Percomorpha-unique among spiny-finned fishes in having evolved placentation and live birth-is especially intriguing.

  3. Identification of g.170G>A and g.332G>A mutations in exon 3 of leptin gene (Bcnl and Cail) and their association with semen quality and testicular dimensions in Sanjabi rams.

    PubMed

    Bakhtiar, Roya; Abdolmohammadi, Alireza; Hajarian, Hadi; Nikousefat, Zahra; Kalantar-Neyestanaki, Davood

    2017-04-01

    The purpose of this study was to investigate leptin gene polymorphisms and their relationships with the characteristics of sperm quality and testicular dimensions. Semen samples were collected from 96 Sanjabi rams during autumn and spring seasons over two years. Simultaneously, the dimensions of length, width and scrotal circumference were measured. Blood samples were taken from the jugular vein to extract DNA. PCR was performed to amplify a 463bp fragment including exon 3 of leptin gene. PCR products were digested by Bcnl and Cail restriction enzymes to identify 170G>A and 332G>A mutations in exon 3, respectively. Leptin gene polymorphism in 170G>A locus had an effect on individual motility trait, water test and scrotal circumference (P<0.05) and animals with the AA genotype had the highest individual motility compared with the GG and GA genotypes (P<0.05). The AG genotypes had the highest water test compared with the GG and AA genotypes (P<0.05) but GG genotype had higher scrotal circumference than that of GA and AA genotypes (P<0.05). The results showed that polymorphism in 332G>A locus had a significant effect on viability trait, water test and scrotal circumference as GA genotypes had the highest amounts for these traits compared with GG genotypes (P<0.05). Based on our knowledge, the current study is the first report on the association of leptin gene polymorphisms with sperm fertility and testicular dimensions in sheep, which suggests leptin gene as a potential gene to be used in breeding programs in order to improve fertility in herds. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A cross-species bi-clustering approach to identifying conserved co-regulated genes

    PubMed Central

    Sun, Jiangwen; Jiang, Zongliang; Tian, Xiuchun; Bi, Jinbo

    2016-01-01

    Motivation: A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approach first identifies gene clusters for each species by a cluster analysis of gene expression data, and subsequently computes the overlaps of clusters identified from different species to reveal common subgroups. This approach is ineffective to deal with the noise in the expression data introduced by the complicated procedures in quantifying gene expression. Furthermore, due to the sequential nature of the approach, the gene clusters identified in the first step may have little overlap among different species in the second step, thus difficult to detect conserved co-regulated genes. Results: We propose a cross-species bi-clustering approach which first denoises the gene expression data of each species into a data matrix. The rows of the data matrices of different species represent the same set of genes that are characterized by their expression patterns over the developmental stages of each species as columns. A novel bi-clustering method is then developed to cluster genes into subgroups by a joint sparse rank-one factorization of all the data matrices. This method decomposes a data matrix into a product of a column vector and a row vector where the column vector is a consistent indicator across the matrices (species) to identify the same gene cluster and the row vector specifies for each species the developmental stages that the clustered genes co-regulate. Efficient optimization algorithm has been developed with convergence analysis. This approach was first validated on

  5. Conserved transcriptional responses to cyanobacterial stressors are mediated by alternate regulation of paralogous genes in Daphnia.

    PubMed

    Asselman, Jana; Pfrender, Michael E; Lopez, Jacqueline A; De Coninck, Dieter I M; Janssen, Colin R; Shaw, Joseph R; De Schamphelaere, Karel A C

    2015-04-01

    Despite a significant increase in genomic data, our knowledge of gene functions and their transcriptional responses to environmental stimuli remains limited. Here, we use the model keystone species Daphnia pulex to study environmental responses of genes in the context of their gene family history to better understand the relationship between genome structure and gene function in response to environmental stimuli. Daphnia were exposed to five different treatments, each consisting of a diet supplemented with one of five cyanobacterial species, and a control treatment consisting of a diet of only green algae. Differential gene expression profiles of Daphnia exposed to each of these five cyanobacterial species showed that genes with known functions are more likely to be shared by different expression profiles, whereas genes specific to the lineage of Daphnia are more likely to be unique to a given expression profile. Furthermore, while only a small number of nonlineage-specific genes were conserved across treatment type, there was a high degree of overlap in expression profiles at the functional level. The conservation of functional responses across the different cyanobacterial treatments can be attributed to the treatment-specific expression of different paralogous genes within the same gene family. Comparison with available gene expression data in the literature suggests differences in nutritional composition in diets with cyanobacterial species compared to diets of green algae as a primary driver for cyanobacterial effects on Daphnia. We conclude that conserved functional responses in Daphnia across different cyanobacterial treatments are mediated through alternate regulation of paralogous gene families. © 2015 John Wiley & Sons Ltd.

  6. Conserved MHC gene orthologs genetically map to the turkey MHC- B.

    PubMed

    Reed, Kent M; Benoit, Benjamin; Wang, Xiong; Greenshields, Molly A; Hughes, Camilla H K; Mendoza, Kristelle M

    2014-01-01

    The avian MHC-associated gene set includes orthologs to genes found throughout the human major histocompatibility complex (MHC), including some loci of the evolutionarily conserved class III region. In the turkey and other Galliformes, genes linked to the MHC have been identified because they are closely associated with class I or class II genes. This study was designed to evaluate additional class III genes for linkage to the avian MHC to further determine conservation of these loci in birds. BLAST searches were used to locate sequences in the turkey genome with similarity to genes shared between the MHC of Xenopus and humans. Primers were designed to target 25 genes, and putative orthologs were amplified by PCR and sequenced. Sequence polymorphisms were identified for 15 genes in turkey reference mapping families, and 8 genes showed significant genetic linkage to the turkey MHC-B locus. These new genetic markers and linkage relationships broaden our understanding of the composition of the avian MHC and expand the gene content for the turkey MHC-B.

  7. Dinoflagellate tandem array gene transcripts are highly conserved and not polycistronic

    PubMed Central

    Beauchemin, Mathieu; Roy, Sougata; Daoust, Philippe; Dagenais-Bellefeuille, Steve; Bertomeu, Thierry; Letourneau, Louis; Lang, B. Franz; Morse, David

    2012-01-01

    Dinoflagellates are an important component of the marine biota, but a large genome with high–copy number (up to 5,000) tandem gene arrays has made genomic sequencing problematic. More importantly, little is known about the expression and conservation of these unusual gene arrays. We assembled de novo a gene catalog of 74,655 contigs for the dinoflagellate Lingulodinium polyedrum from RNA-Seq (Illumina) reads. The catalog contains 93% of a Lingulodinium EST dataset deposited in GenBank and 94% of the enzymes in 16 primary metabolic KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, indicating it is a good representation of the transcriptome. Analysis of the catalog shows a marked underrepresentation of DNA-binding proteins and DNA-binding domains compared with other algae. Despite this, we found no evidence to support the proposal of polycistronic transcription, including a marked underrepresentation of sequences corresponding to the intergenic spacers of two tandem array genes. We also have used RNA-Seq to assess the degree of sequence conservation in tandem array genes and found their transcripts to be highly conserved. Interestingly, some of the sequences in the catalog have only bacterial homologs and are potential candidates for horizontal gene transfer. These presumably were transferred as single-copy genes, and because they are now all GC-rich, any derived from AT-rich contexts must have experienced extensive mutation. Our study not only has provided the most complete dinoflagellate gene catalog known to date, it has also exploited RNA-Seq to address fundamental issues in basic transcription mechanisms and sequence conservation in these algae. PMID:23019363

  8. Expression patterns of TEL genes in Poaceae suggest a conserved association with cell differentiation.

    PubMed

    Paquet, Nicolas; Bernadet, Marie; Morin, Halima; Traas, Jan; Dron, Michel; Charon, Celine

    2005-06-01

    Poaceae species present a conserved distichous phyllotaxy (leaf position along the stem) and share common properties with respect to leaf initiation. The goal of this work was to determine if these common traits imply common genes. Therefore, homologues of the maize TERMINAL EAR1 gene in Poaceae were studied. This gene encodes an RNA-binding motif (RRM) protein, that is suggested to regulate leaf initiation. Using degenerate primers, one unique tel (terminal ear1-like) gene from seven Poaceae members, covering almost all the phylogenetic tree of the family, was identified by PCR. These genes present a very high degree of similarity, a much conserved exon-intron structure, and the three RRMs and TEL characteristic motifs. The evolution of tel sequences in Poaceae strongly correlates with the known phylogenetic tree of this family. RT-PCR gene expression analyses show conserved tel expression in the shoot apex in all species, suggesting functional orthology between these genes. In addition, in situ hybridization experiments with specific antisense probes show tel transcript accumulation in all differentiating cells of the leaf, from the recruitment of leaf founder cells to leaf margins cells. Tel expression is not restricted to initiating leaves as it is also found in pro-vascular tissues, root meristems, and immature inflorescences. Therefore, these results suggest that TEL is not only associated with leaf initiation but more generally with cell differentiation in Poaceae.

  9. Eleven ancestral gene families lost in mammals and vertebrates while otherwise universally conserved in animals

    PubMed Central

    Danchin, Etienne GJ; Gouret, Philippe; Pontarotti, Pierre

    2006-01-01

    Background Gene losses played a role which may have been as important as gene and genome duplications and rearrangements, in modelling today species' genomes from a common ancestral set of genes. The set and diversity of protein-coding genes in a species has direct output at the functional level. While gene losses have been reported in all the major lineages of the metazoan tree of life, none have proposed a focus on specific losses in the vertebrates and mammals lineages. In contrast, genes lost in protostomes (i.e. arthropods and nematodes) but still present in vertebrates have been reported and extensively detailed. This probable over-anthropocentric way of comparing genomes does not consider as an important phenomena, gene losses in species that are usually described as "higher". However reporting universally conserved genes throughout evolution that have recently been lost in vertebrates and mammals could reveal interesting features about the evolution of our genome, particularly if these losses can be related to losses of capability. Results We report 11 gene families conserved throughout eukaryotes from yeasts (such as Saccharomyces cerevisiae) to bilaterian animals (such as Drosophila melanogaster or Caenorhabditis elegans). This evolutionarily wide conservation suggests they were present in the last common ancestors of fungi and metazoan animals. None of these 11 gene families are found in human nor mouse genomes, and their absence generally extends to all vertebrates. A total of 8 out of these 11 gene families have orthologs in plants, suggesting they were present in the Last Eukaryotic Common Ancestor (LECA). We investigated known functional information for these 11 gene families. This allowed us to correlate some of the lost gene families to loss of capabilities. Conclusion Mammalian and vertebrate genomes lost evolutionary conserved ancestral genes that are probably otherwise not dispensable in eukaryotes. Hence, the human genome, which is generally

  10. Syntenic conservation of HSP70 genes in cattle and humans

    SciTech Connect

    Grosz, M.D.; Womack, J.E.; Skow, L.C. )

    1992-12-01

    A phage library of bovine genomic DNA was screened for hybridization with a human HSP70 cDNA probe, and 21 positive plaques were identified and isolated. Restriction mapping and blot hybridization analysis of DNA from the recombinant plaques demonstrated that the cloned DNAs were derived from three different regions of the bovine genome. Ore region contains two tandemly arrayed HSP70 sequences, designated HSP70-1 and HSP70-2, separated by approximately 8 kb of DNA. Single HSP70 sequences, designated HSP70-3 and HSP70-4, were found in two other genomic regions. Locus-specific probes of unique flanking sequences from representative HSP70 clones were hybridized to restriction endonuclease-digested DNA from bovine-hamster and bovine-mouse somatic cell hybrid panels to determine the chromosomal location of the HSP70 sequences. The probe for the tandemly arrayed HSP70-1 and HSP70-2 sequences mapped to bovine chromosome 23, syntenic with glyoxalase 1, 21 steroid hydroxylase, and major histocompatibility class I loci. HSP70-3 sequences mapped to bovine chromosome 10, syntenic with nucleoside phosphorylase and murine osteosarcoma viral oncogene (v-fos), and HSP70-4 mapped to bovine syntenic group U6, syntenic with amylase 1 and phosphoglucomutase 1. On the basis of these data, the authors propose that bovine HSP70-1,2 are homologous to human HSPA1 and HSPA1L on chromosome 6p21.3, bovine HSP70-3 is the homolog of an unnamed human HSP70 gene on chromosome 14q22-q24, and bovine HSP70-4 is homologous to one of the human HSPA-6,-7 genes on chromosome 1. 34 refs., 2 figs., 1 tab.

  11. Propolis attenuates doxorubicin-induced testicular toxicity in rats.

    PubMed

    Rizk, Sherine M; Zaki, Hala F; Mina, Mary A M

    2014-05-01

    Doxorubicin (Dox), an effective anticancer agent, can impair testicular function leading to infertility. The present study aimed to explore the protective effect of propolis extract on Dox-induced testicular injury. Rats were divided into four groups (n=10). Group I (normal control), group II received propolis extract (200 mg kg(-1); p.o.), for 3 weeks. Group III received 18 mg kg(-1) total cumulative dose of Dox i.p. Group IV received Dox and propolis extract. Serum and testicular samples were collected 48 h after the last treatment. In addition, the effects of propolis extract and Dox on the growth of solid Ehrlich carcinoma in mice were investigated. Dox reduced sperm count, markers of testicular function, steroidogenesis and gene expression of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) and steroidogenic acute regulatory protein (StAR). In addition, it increased testicular oxidative stress, inflammatory and apoptotic markers. Morphometric and histopathologic studies supported the biochemical findings. Treatment with propolis extract prevented Dox-induced changes without reducing its antitumor activity. Besides, administration of propolis extract to normal rats increased serum testosterone level coupled by increased activities and gene expression of 3ß-HSD and 17ß-HSD. Propolis extract may protect the testis from Dox-induced toxicity without reducing its anticancer potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Conservation of the b mating-type gene complex among bipolar and tetrapolar smut fungi.

    PubMed Central

    Bakkeren, G; Kronstad, J W

    1993-01-01

    In the phytopathogenic fungus Ustilago hordei, one locus with two alternate alleles, MAT-1 and MAT-2, controls mating and the establishment of the infectious dikaryon (bipolar mating). In contrast, for U. maydis, these functions are associated with two different gene complexes, called a and b (tetrapolar mating); the a complex has two alternate specificities, and the b gene complex is multiallelic. We have found homologs for the b gene complex in U. hordei and have cloned one from each mating type using sequences from one bEast allele of U. maydis as a probe. Sequence analysis revealed two divergent open reading frames in each b complex, which we called bW (bWest) and bE (bEast) in analogy with the b gene complex of U. maydis. The predicted bW and bE gene products from the two different mating types showed approximately 75% identity when homologous polypeptides were compared. All of the characterized bW and bE gene products have variable amino-terminal regions, conserved carboxy-terminal regions, and similar homeodomain motifs. Sequence comparisons with the bW1 and bE1 genes of U. maydis showed conservation in organization and structure. Transformation of the U. hordei b gene complex into a U. hordei strain of opposite mating type showed that the b genes from the two mating types are functional alleles. The U. hordei b genes, when introduced into U. maydis, rendered the haploid transformants weakly pathogenic on maize. These results indicate that structurally and functionally conserved b genes are present in U. hordei. PMID:8439742

  13. Identification and analysis of a highly conserved chemotaxis gene cluster in Shewanella species.

    SciTech Connect

    Li, J.; Romine, Margaret F.; Ward, M.

    2007-08-01

    A conserved cluster of chemotaxis genes was identified from the genome sequences of fifteen Shewanella species. An in-frame deletion of the cheA-3 gene, which is located in this cluster, was created in S. oneidensis MR-1 and the gene shown to be essential for chemotactic responses to anaerobic electron acceptors. The CheA-3 protein showed strong similarity to Vibrio cholerae CheA-2 and P. aeruginosa CheA-1, two proteins that are also essential for chemotaxis. The genes encoding these proteins were shown to be located in chemotaxis gene clusters closely related to the cheA-3-containing cluster in Shewanella species. The results of this study suggest that a combination of gene neighborhood and homology analyses may be used to predict which cheA genes are essential for chemotaxis in groups of closely related microorganisms.

  14. Deciphering the onychophoran 'segmentation gene cascade': Gene expression reveals limited involvement of pair rule gene orthologs in segmentation, but a highly conserved segment polarity gene network.

    PubMed

    Janssen, Ralf; Budd, Graham E

    2013-10-01

    The hallmark of the arthropods is their segmented body, although origin of segmentation, however, is unresolved. In order to shed light on the origin of segmentation we investigated orthologs of pair rule genes (PRGs) and segment polarity genes (SPGs) in a member of the closest related sister-group to the arthropods, the onychophorans. Our gene expression data analysis suggests that most of the onychophoran PRGs do not play a role in segmentation. One possible exception is the even-skipped (eve) gene that is expressed in the posterior end of the onychophoran where new segments are likely patterned, and is also expressed in segmentation-gene typical transverse stripes in at least a number of newly formed segments. Other onychophoran PRGs such as runt (run), hairy/Hes (h/Hes) and odd-skipped (odd) do not appear to have a function in segmentation at all. Onychophoran PRGs that act low in the segmentation gene cascade in insects, however, are potentially involved in segment-patterning. Most obvious is that from the expression of the pairberry (pby) gene ortholog that is expressed in a typical SPG-pattern. Since this result suggested possible conservation of the SPG-network we further investigated SPGs (and associated factors) such as Notum in the onychophoran. We find that the expression patterns of SPGs in arthropods and the onychophoran are highly conserved, suggesting a conserved SPG-network in these two clades, and indeed also in an annelid. This may suggest that the common ancestor of lophotrochozoans and ecdysozoans was already segmented utilising the same SPG-network, or that the SPG-network was recruited independently in annelids and onychophorans/arthropods.

  15. Highly conserved low-copy nuclear genes as effective markers for phylogenetic analyses in angiosperms.

    PubMed

    Zhang, Ning; Zeng, Liping; Shan, Hongyan; Ma, Hong

    2012-09-01

    Organismal phylogeny provides a crucial evolutionary framework for many studies and the angiosperm phylogeny has been greatly improved recently, largely using organellar and rDNA genes. However, low-copy protein-coding nuclear genes have not been widely used on a large scale in spite of the advantages of their biparental inheritance and vast number of choices. Here, we identified 1083 highly conserved low-copy nuclear genes by genome comparison. Furthermore, we demonstrated the use of five nuclear genes in 91 angiosperms representing 46 orders (73% of orders) and three gymnosperms as outgroups for a highly resolved phylogeny. These nuclear genes are easy to clone and align, and more phylogenetically informative than widely used organellar genes. The angiosperm phylogeny reconstructed using these genes was largely congruent with previous ones mainly inferred from organellar genes. Intriguingly, several new placements were uncovered for some groups, including those among the rosids, the asterids, and between the eudicots and several basal angiosperm groups. These conserved universal nuclear genes have several inherent qualities enabling them to be good markers for reconstructing angiosperm phylogeny, even eukaryotic relationships, further providing new insights into the evolutionary history of angiosperms.

  16. Conserved miR164-targeted NAC genes negatively regulate drought resistance in rice.

    PubMed

    Fang, Yujie; Xie, Kabin; Xiong, Lizhong

    2014-05-01

    MicroRNAs constitute a large group of endogenous small RNAs of ~22 nt that emerge as vital regulators, mainly by targeting mRNAs for post-transcriptional repression. Previous studies have revealed that the miR164 family in Arabidopsis is comprised of three members which guide the cleavage of the mRNAs of five NAC genes to modulate developmental processes. However, the functions of the miR164-targeted NAC genes in crops are poorly deciphered. In this study, the conserved features of six miR164-targeted NAC genes (OMTN1-OMTN6) in rice are described, and evidence is provided that four of them confer a negative regulatory role in drought resistance. OMTN proteins have the characteristics of typical NAC transcriptional factors. The miR164 recognition sites of the OMTN genes are highly conserved in rice germplasms. Deletion of the recognition sites impaired the transactivation activity, indicating that the conserved recognition sites play a crucial role in maintaining the function of the OMTN proteins. The OMTN genes were responsive to abiotic stresses, and showed diverse spatio-temporal expression patterns in rice. Overexpression of OMTN2, OMTN3, OMTN4, and OMTN6 in rice led to negative effects on drought resistance at the reproductive stage. The expression of numerous genes related to stress response, development, and metabolism was altered in OMTN2-, OMTN3-, OMTN4-, and OMTN6-overexpressing plants. Most of the up-regulated genes in the OMTN-overexpressing plants were down-regulated by drought stress. The results suggest that the conserved miR164-targeted NAC genes may be negative regulators of drought tolerance in rice, in addition to their reported roles in development.

  17. Testicular cancer in cryptorchids.

    PubMed

    Batata, M A; Chu, F C; Hilaris, B S; Whitmore, W F; Golbey, R B

    1982-03-01

    One-hundred thirty-seven patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor were treated at our hospital from 1934 to 1976. Cryptorchidism was corrected ipsilaterally or contralaterally in 93 patients with intrascrotal testis cancer when they were from 2 to 42 years old, either spontaneously (24 patients), by orchiopexy (58 patients), or by hormonal therapy (11 patients). Forty-four cryptorchid patients (uncorrected cases) had either ipsilateral inguinal (24 patients), or abdominal (14 patients), or contralateral intrascrotal tumors (six patients). Tumor histologic types on orchiectomy were pure seminoma in 56 patients, embryonal carcinoma in 41, teratocarcinoma in 37, and pure choriocarcinoma in 3. The five-year survival rates were similar in the corrected (61%) and uncorrected (63%) cases, and they were higher in patients with pure seminoma (79%) than in patients with germinal carcinomas (50%). The majority (64 of 80) of five-year survivors received regional lymphatic irradiation in 41 patients with pure seminoma and/or systemic chemotherapy in 23 patients with other germinomas. Since the testicular tumors that developed despite correction of the cryptorchid state were predominantly (72%) germinal carcinomas, unilateral cryptorchidism, which usually is associated with testicular atrophy, should be treated by orchiectomy instead of orchiopexy to prevent ipsilateral carcinogenesis. Cryptorchid patients with testicles that descended late should be observed periodically, especially after the 20-year latent period, for early detection of cancer.

  18. Drug repositioning for orphan genetic diseases through Conserved Anticoexpressed Gene Clusters (CAGCs)

    PubMed Central

    2013-01-01

    Background The development of new therapies for orphan genetic diseases represents an extremely important medical and social challenge. Drug repositioning, i.e. finding new indications for approved drugs, could be one of the most cost- and time-effective strategies to cope with this problem, at least in a subset of cases. Therefore, many computational approaches based on the analysis of high throughput gene expression data have so far been proposed to reposition available drugs. However, most of these methods require gene expression profiles directly relevant to the pathologic conditions under study, such as those obtained from patient cells and/or from suitable experimental models. In this work we have developed a new approach for drug repositioning, based on identifying known drug targets showing conserved anti-correlated expression profiles with human disease genes, which is completely independent from the availability of ‘ad hoc’ gene expression data-sets. Results By analyzing available data, we provide evidence that the genes displaying conserved anti-correlation with drug targets are antagonistically modulated in their expression by treatment with the relevant drugs. We then identified clusters of genes associated to similar phenotypes and showing conserved anticorrelation with drug targets. On this basis, we generated a list of potential candidate drug-disease associations. Importantly, we show that some of the proposed associations are already supported by independent experimental evidence. Conclusions Our results support the hypothesis that the identification of gene clusters showing conserved anticorrelation with drug targets can be an effective method for drug repositioning and provide a wide list of new potential drug-disease associations for experimental validation. PMID:24088245

  19. A Collection of Conserved Noncoding Sequences to Study Gene Regulation in Flowering Plants1[OPEN

    PubMed Central

    2016-01-01

    Transcription factors (TFs) regulate gene expression by binding cis-regulatory elements, of which the identification remains an ongoing challenge owing to the prevalence of large numbers of nonfunctional TF binding sites. Powerful comparative genomics methods, such as phylogenetic footprinting, can be used for the detection of conserved noncoding sequences (CNSs), which are functionally constrained and can greatly help in reducing the number of false-positive elements. In this study, we applied a phylogenetic footprinting approach for the identification of CNSs in 10 dicot plants, yielding 1,032,291 CNSs associated with 243,187 genes. To annotate CNSs with TF binding sites, we made use of binding site information for 642 TFs originating from 35 TF families in Arabidopsis (Arabidopsis thaliana). In three species, the identified CNSs were evaluated using TF chromatin immunoprecipitation sequencing data, resulting in significant overlap for the majority of data sets. To identify ultraconserved CNSs, we included genomes of additional plant families and identified 715 binding sites for 501 genes conserved in dicots, monocots, mosses, and green algae. Additionally, we found that genes that are part of conserved mini-regulons have a higher coherence in their expression profile than other divergent gene pairs. All identified CNSs were integrated in the PLAZA 3.0 Dicots comparative genomics platform (http://bioinformatics.psb.ugent.be/plaza/versions/plaza_v3_dicots/) together with new functionalities facilitating the exploration of conserved cis-regulatory elements and their associated genes. The availability of this data set in a user-friendly platform enables the exploration of functional noncoding DNA to study gene regulation in a variety of plant species, including crops. PMID:27261064

  20. A subset of conserved tRNA genes in plastid DNA of nongreen plants.

    PubMed

    Lohan, A J; Wolfe, K H

    1998-09-01

    The plastid genome of the nonphotosynthetic parasitic plant Epifagus virginiana contains only 17 of the 30 tRNA genes normally found in angiosperm plastid DNA. Although this is insufficient for translation, the genome is functional, so import of cytosolic tRNAs into plastids has been suggested. This raises the question of whether the tRNA genes that remain in E. virginiana plastid DNA are active or have just fortuitously escaped deletion. We report the sequences of 20 plastid tRNA loci from Orobanche minor, which shares a nonphotosynthetic ancestor with E. virginiana. The two species have 9 intact tRNA genes in common, the others being defunct in one or both species. The intron-containing trnLUAA gene is absent from E. virginiana, but it is intact, transcribed, and spliced in O. minor. The shared intact genes are better conserved than intergenic sequences, which indicates that these genes are being maintained by natural selection and, therefore, must be functional. For the most part, the tRNA species conserved in nonphotosynthetic plastids are also those that have never been found to be imported in plant mitochondria, which suggests that the same rules may govern tRNA import in the two organelles. A small photosynthesis gene, psbI, is still intact in O. minor, and computer simulations show that some small nonessential genes have an appreciable chance of escaping deletion.

  1. A subset of conserved tRNA genes in plastid DNA of nongreen plants.

    PubMed Central

    Lohan, A J; Wolfe, K H

    1998-01-01

    The plastid genome of the nonphotosynthetic parasitic plant Epifagus virginiana contains only 17 of the 30 tRNA genes normally found in angiosperm plastid DNA. Although this is insufficient for translation, the genome is functional, so import of cytosolic tRNAs into plastids has been suggested. This raises the question of whether the tRNA genes that remain in E. virginiana plastid DNA are active or have just fortuitously escaped deletion. We report the sequences of 20 plastid tRNA loci from Orobanche minor, which shares a nonphotosynthetic ancestor with E. virginiana. The two species have 9 intact tRNA genes in common, the others being defunct in one or both species. The intron-containing trnLUAA gene is absent from E. virginiana, but it is intact, transcribed, and spliced in O. minor. The shared intact genes are better conserved than intergenic sequences, which indicates that these genes are being maintained by natural selection and, therefore, must be functional. For the most part, the tRNA species conserved in nonphotosynthetic plastids are also those that have never been found to be imported in plant mitochondria, which suggests that the same rules may govern tRNA import in the two organelles. A small photosynthesis gene, psbI, is still intact in O. minor, and computer simulations show that some small nonessential genes have an appreciable chance of escaping deletion. PMID:9725858

  2. Comprehensive analysis of animal TALE homeobox genes: new conserved motifs and cases of accelerated evolution.

    PubMed

    Mukherjee, Krishanu; Bürglin, Thomas R

    2007-08-01

    TALE homeodomain proteins are an ancient subgroup within the group of homeodomain transcription factors that play important roles in animal, plant, and fungal development. We have extracted the full complement of TALE superclass homeobox genes from the genome projects of seven protostomes, seven deuterostomes, and Nematostella. This was supplemented with TALE homeobox genes from additional species and phylogenetic analyses were carried out with 276 sequences. We found 20 homeobox genes and 4 pseudogenes in humans, 21 genes in mouse, 8 genes in Drosophila, and 5 genes plus one truncated gene in Caenorhabditis elegans. Apart from the previously identified TALE classes MEIS, PBC, IRO, and TGIF, a novel class is identified, termed MOHAWK (MKX). Further, we show that the MEIS class can be divided into two families, PREP and MEIS. Prep genes have previously only been described in vertebrates but are lacking in Drosophila. Here we identify orthologues in other insect taxa as well as in the cnidarian Nematostella. In C. elegans, a divergent Prep protein has lost the homeodomain. Full-length multiple sequence alignment of the protostome and deuterostome sequences allowed us to identify several novel conserved motifs within the MKX, TGIF, and MEIS classes. Phylogenetic analyses revealed fast-evolving PBC class genes; in particular, some X-linked PBC genes in nematodes are subject to rapid evolution. In addition, several instances of gene loss were identified. In conclusion, our comprehensive analysis provides a defining framework for the classification of animal TALE homeobox genes and the understanding of their evolution.

  3. Ultrasonography of Extravaginal Testicular Torsion in Neonates

    PubMed Central

    Bombiński, Przemysław; Warchoł, Stanisław; Brzewski, Michał; Majkowska, Zofia; Dudek-Warchoł, Teresa; Żerańska, Maria; Panek, Małgorzata; Drop, Magdalena

    2016-01-01

    Summary Background Extravaginal testicular torsion (ETT), also called prenatal or perinatal, occurs prenatally and is present at birth or appears within the first month of life. It has different etiology than intravaginal torsion, which appears later in life. Testicular torsion must be taken into consideration in differential diagnosis of acute scrotum and should be confirmed or ruled out at first diagnostic step. Ultrasonography is a basic imaging modality, however diagnostic pitfalls are still possible. There is still wide discussion concerning management of ETT, which varies from immediate orchiectomy to conservative treatment resulting in testicle atrophy. Material/Methods In this article we present ultrasonographic spectrum of ETT in neonates, which were diagnosed and treated in our hospital during the last 8 years (2008–2015), in correlation with clinical and intraoperative findings. Results Thirteen neonates with ETT were enrolled in the study – 11 patients with a single testicle affected and 2 patients with bilateral testicular torsion. Most common signs on clinical examination were: hardened and enlarged testicle and discoloration of the scrotum. Most common ultrasonographic signs were: abnormal size or echostructure of the affected testicle and absence of the blood flow in Doppler ultrasonography. In 3 patients ultrasound elastography was performed, which appeared very useful in testicle structure assessment. Conclusions Testicular torsion may concern boys even in the perinatal period. Ultrasonographic picture of acute scrotum in young boys may be confused. Coexistence of the abnormal size or echostructure of the torsed testicle with absence of the blood flow in Doppler ultrasonography appear as very specific but late ultrasonographic sings. Ultrasound elastography may be a very useful tool for visualisation of a very common clinical sign – hardening of the necrotic testicle. PMID:27757176

  4. Identification of a conserved sequence in the non-coding regions of many human genes.

    PubMed Central

    Donehower, L A; Slagle, B L; Wilde, M; Darlington, G; Butel, J S

    1989-01-01

    We have analyzed a sequence of approximately 70 base pairs (bp) that shows a high degree of similarity to sequences present in the non-coding regions of a number of human and other mammalian genes. The sequence was discovered in a fragment of human genomic DNA adjacent to an integrated hepatitis B virus genome in cells derived from human hepatocellular carcinoma tissue. When one of the viral flanking sequences was compared to nucleotide sequences in GenBank, more than thirty human genes were identified that contained a similar sequence in their non-coding regions. The sequence element was usually found once or twice in a gene, either in an intron or in the 5' or 3' flanking regions. It did not share any similarities with known short interspersed nucleotide elements (SINEs) or presently known gene regulatory elements. This element was highly conserved at the same position within the corresponding human and mouse genes for myoglobin and N-myc, indicating evolutionary conservation and possible functional importance. Preliminary DNase I footprinting data suggested that the element or its adjacent sequences may bind nuclear factors to generate specific DNase I hypersensitive sites. The size, structure, and evolutionary conservation of this sequence indicates that it is distinct from other types of short interspersed repetitive elements. It is possible that the element may have a cis-acting functional role in the genome. Images PMID:2536922

  5. Cordon-bleu is a conserved gene involved in neural tube formation.

    PubMed

    Carroll, Elizabeth A; Gerrelli, Dianne; Gasca, Stéphan; Berg, Elizabeth; Beier, David R; Copp, Andrew J; Klingensmith, John

    2003-10-01

    The axial midline is an important source of patterning and morphogenesis cues in the vertebrate embryo. The midline derives from a small group of cells in the gastrulating embryo, known as "the organizer" in recognition of its ability to organize an entire body plan. The mammalian organizer, the node, gives rise to axial midline structures: the notochord, dorsal foregut, and part of the floor plate of the neural tube. Only some of the genes that direct midline development are known. In this study, we present the complete coding sequence for a novel gene, cordon-bleu (cobl), expressed specifically in the node and its derivatives until organogenesis stages. The deduced sequence does not resemble any gene of known function. However, cobl is widely conserved: apparent orthologs and paralogs are found in many vertebrate species, with several sequence domains of high conservation but unknown function. We find that chicken cordon-bleu is similarly expressed in the node and its derivatives, suggesting functional conservation. We also report the sequence and nonoverlapping expression of a related mouse gene, Coblr1. Finally, we show that cobl interacts with the neurulation gene Vangl2 to facilitate midbrain neural tube closure, demonstrating roles for both cobl and Vangl2 in midbrain neurulation.

  6. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    PubMed Central

    Fauteux, François; Strömvik, Martina V

    2009-01-01

    Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

  7. Low Temperature-Induced Circulating Triiodothyronine Accelerates Seasonal Testicular Regression

    PubMed Central

    Ikegami, Keisuke; Atsumi, Yusuke; Yorinaga, Eriko; Ono, Hiroko; Murayama, Itaru; Nakane, Yusuke; Ota, Wataru; Arai, Natsumi; Tega, Akinori; Iigo, Masayuki; Darras, Veerle M.; Tsutsui, Kazuyoshi; Hayashi, Yoshitaka; Yoshida, Shosei

    2015-01-01

    In temperate zones, animals restrict breeding to specific seasons to maximize the survival of their offspring. Birds have evolved highly sophisticated mechanisms of seasonal regulation, and their testicular mass can change 100-fold within a few weeks. Recent studies on Japanese quail revealed that seasonal gonadal development is regulated by central thyroid hormone activation within the hypothalamus, depending on the photoperiodic changes. By contrast, the mechanisms underlying seasonal testicular regression remain unclear. Here we show the effects of short day and low temperature on testicular regression in quail. Low temperature stimulus accelerated short day-induced testicular regression by shutting down the hypothalamus-pituitary-gonadal axis and inducing meiotic arrest and germ cell apoptosis. Induction of T3 coincided with the climax of testicular regression. Temporal gene expression analysis over the course of apoptosis revealed the suppression of LH response genes and activation of T3 response genes involved in amphibian metamorphosis within the testis. Daily ip administration of T3 mimicked the effects of low temperature stimulus on germ cell apoptosis and testicular mass. Although type 2 deiodinase, a thyroid hormone-activating enzyme, in the brown adipose tissue generates circulating T3 under low-temperature conditions in mammals, there is no distinct brown adipose tissue in birds. In birds, type 2 deiodinase is induced by low temperature exclusively in the liver, which appears to be caused by increased food consumption. We conclude that birds use low temperature-induced circulating T3 not only for adaptive thermoregulation but also to trigger apoptosis to accelerate seasonal testicular regression. PMID:25406020

  8. Paradoxical DNA Repair and Peroxide Resistance Gene Conservation in Bacillus pumilus SAFR-032

    PubMed Central

    Qin, Xiang; Jiang, Huaiyang; Igboeli, Okezie C.; Muzny, Donna; Dugan-Rocha, Shannon; Ding, Yan; Hawes, Alicia; Liu, Wen; Perez, Lesette; Kovar, Christie; Dinh, Huyen; Lee, Sandra; Nazareth, Lynne; Blyth, Peter; Holder, Michael; Buhay, Christian; Tirumalai, Madhan R.; Liu, Yamei; Dasgupta, Indrani; Bokhetache, Lina; Fujita, Masaya; Karouia, Fathi; Eswara Moorthy, Prahathees; Siefert, Johnathan; Uzman, Akif; Buzumbo, Prince; Verma, Avani; Zwiya, Hiba; McWilliams, Brian D.; Olowu, Adeola; Clinkenbeard, Kenneth D.; Newcombe, David; Golebiewski, Lisa; Petrosino, Joseph F.; Nicholson, Wayne L.; Fox, George E.; Venkateswaran, Kasthuri; Highlander, Sarah K.; Weinstock, George M.

    2007-01-01

    Background Bacillus spores are notoriously resistant to unfavorable conditions such as UV radiation, γ-radiation, H2O2, desiccation, chemical disinfection, or starvation. Bacillus pumilus SAFR-032 survives standard decontamination procedures of the Jet Propulsion Lab spacecraft assembly facility, and both spores and vegetative cells of this strain exhibit elevated resistance to UV radiation and H2O2 compared to other Bacillus species. Principal Findings The genome of B. pumilus SAFR-032 was sequenced and annotated. Lists of genes relevant to DNA repair and the oxidative stress response were generated and compared to B. subtilis and B. licheniformis. Differences in conservation of genes, gene order, and protein sequences are highlighted because they potentially explain the extreme resistance phenotype of B. pumilus. The B. pumilus genome includes genes not found in B. subtilis or B. licheniformis and conserved genes with sequence divergence, but paradoxically lacks several genes that function in UV or H2O2 resistance in other Bacillus species. Significance This study identifies several candidate genes for further research into UV and H2O2 resistance. These findings will help explain the resistance of B. pumilus and are applicable to understanding sterilization survival strategies of microbes. PMID:17895969

  9. Conservation and Diversification of an Ancestral Chordate Gene Regulatory Network for Dorsoventral Patterning

    PubMed Central

    Kozmikova, Iryna; Smolikova, Jana; Vlcek, Cestmir; Kozmik, Zbynek

    2011-01-01

    Formation of a dorsoventral axis is a key event in the early development of most animal embryos. It is well established that bone morphogenetic proteins (Bmps) and Wnts are key mediators of dorsoventral patterning in vertebrates. In the cephalochordate amphioxus, genes encoding Bmps and transcription factors downstream of Bmp signaling such as Vent are expressed in patterns reminiscent of those of their vertebrate orthologues. However, the key question is whether the conservation of expression patterns of network constituents implies conservation of functional network interactions, and if so, how an increased functional complexity can evolve. Using heterologous systems, namely by reporter gene assays in mammalian cell lines and by transgenesis in medaka fish, we have compared the gene regulatory network implicated in dorsoventral patterning of the basal chordate amphioxus and vertebrates. We found that Bmp but not canonical Wnt signaling regulates promoters of genes encoding homeodomain proteins AmphiVent1 and AmphiVent2. Furthermore, AmphiVent1 and AmphiVent2 promoters appear to be correctly regulated in the context of a vertebrate embryo. Finally, we show that AmphiVent1 is able to directly repress promoters of AmphiGoosecoid and AmphiChordin genes. Repression of genes encoding dorsal-specific signaling molecule Chordin and transcription factor Goosecoid by Xenopus and zebrafish Vent genes represents a key regulatory interaction during vertebrate axis formation. Our data indicate high evolutionary conservation of a core Bmp-triggered gene regulatory network for dorsoventral patterning in chordates and suggest that co-option of the canonical Wnt signaling pathway for dorsoventral patterning in vertebrates represents one of the innovations through which an increased morphological complexity of vertebrate embryo is achieved. PMID:21304903

  10. A tree of life based on ninety-eight expressed genes conserved across diverse eukaryotic species

    PubMed Central

    Jayaswal, Pawan Kumar; Dogra, Vivek; Shanker, Asheesh; Sharma, Tilak Raj

    2017-01-01

    Rapid advances in DNA sequencing technologies have resulted in the accumulation of large data sets in the public domain, facilitating comparative studies to provide novel insights into the evolution of life. Phylogenetic studies across the eukaryotic taxa have been reported but on the basis of a limited number of genes. Here we present a genome-wide analysis across different plant, fungal, protist, and animal species, with reference to the 36,002 expressed genes of the rice genome. Our analysis revealed 9831 genes unique to rice and 98 genes conserved across all 49 eukaryotic species analysed. The 98 genes conserved across diverse eukaryotes mostly exhibited binding and catalytic activities and shared common sequence motifs; and hence appeared to have a common origin. The 98 conserved genes belonged to 22 functional gene families including 26S protease, actin, ADP–ribosylation factor, ATP synthase, casein kinase, DEAD-box protein, DnaK, elongation factor 2, glyceraldehyde 3-phosphate, phosphatase 2A, ras-related protein, Ser/Thr protein phosphatase family protein, tubulin, ubiquitin and others. The consensus Bayesian eukaryotic tree of life developed in this study demonstrated widely separated clades of plants, fungi, and animals. Musa acuminata provided an evolutionary link between monocotyledons and dicotyledons, and Salpingoeca rosetta provided an evolutionary link between fungi and animals, which indicating that protozoan species are close relatives of fungi and animals. The divergence times for 1176 species pairs were estimated accurately by integrating fossil information with synonymous substitution rates in the comprehensive set of 98 genes. The present study provides valuable insight into the evolution of eukaryotes. PMID:28922368

  11. The Atrazine Catabolism Genes atzABC Are Widespread and Highly Conserved

    PubMed Central

    de Souza, Mervyn L.; Seffernick, Jennifer; Martinez, Betsy; Sadowsky, Michael J.; Wackett, Lawrence P.

    1998-01-01

    Pseudomonas strain ADP metabolizes the herbicide atrazine via three enzymatic steps, encoded by the genes atzABC, to yield cyanuric acid, a nitrogen source for many bacteria. Here, we show that five geographically distinct atrazine-degrading bacteria contain genes homologous to atzA, -B, and -C. The sequence identities of the atz genes from different atrazine-degrading bacteria were greater than 99% in all pairwise comparisons. This differs from bacterial genes involved in the catabolism of other chlorinated compounds, for which the average sequence identity in pairwise comparisons of the known members of a class ranged from 25 to 56%. Our results indicate that globally distributed atrazine-catabolic genes are highly conserved in diverse genera of bacteria. PMID:9537398

  12. Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu.

    PubMed

    Dasgupta, Ujjaini; Dixit, Bharat L; Rusch, Melissa; Selleck, Scott; The, Inge

    2007-08-01

    Heparan sulfate proteoglycans play a vital role in signaling of various growth factors in both Drosophila and vertebrates. In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG) biosynthesis. This impairs distribution and signaling activities of various morphogens such as Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Mutations in members of the exostosin (EXT) gene family lead to hereditary multiple exostosis in humans leading to bone outgrowths and tumors. In this study, we provide genetic and biochemical evidence that the human EXT1 (hEXT1) gene is conserved through species and can functionally complement the ttv mutation in Drosophila. The hEXT1 gene was able to rescue a ttv null mutant to adulthood and restore GAG biosynthesis.

  13. Conservation of Pax gene expression in ectodermal placodes of the lamprey

    NASA Technical Reports Server (NTRS)

    McCauley, David W.; Bronner-Fraser, Marianne

    2002-01-01

    Ectodermal placodes contribute to the cranial ganglia and sense organs of the head and, together with neural crest cells, represent defining features of the vertebrate embryo. The identity of different placodes appears to be specified in part by the expression of different Pax genes, with Pax-3/7 class genes being expressed in the trigeminal placode of mice, chick, frogs and fish, and Pax-2/5/8 class genes expressed in the otic placode. Here, we present the cloning and expression pattern of lamprey Pax-7 and Pax-2, which mark the trigeminal and otic placodes, respectively, as well as other structures characteristic of vertebrate Pax genes. These results suggest conservation of Pax genes and placodal structures in basal and derived vertebrates.

  14. Conservation of Pax gene expression in ectodermal placodes of the lamprey.

    PubMed

    McCauley, David W; Bronner-Fraser, Marianne

    2002-04-03

    Ectodermal placodes contribute to the cranial ganglia and sense organs of the head and, together with neural crest cells, represent defining features of the vertebrate embryo. The identity of different placodes appears to be specified in part by the expression of different Pax genes, with Pax-3/7 class genes being expressed in the trigeminal placode of mice, chick, frogs and fish, and Pax-2/5/8 class genes expressed in the otic placode. Here, we present the cloning and expression pattern of lamprey Pax-7 and Pax-2, which mark the trigeminal and otic placodes, respectively, as well as other structures characteristic of vertebrate Pax genes. These results suggest conservation of Pax genes and placodal structures in basal and derived vertebrates.

  15. Regulation of SHOOT MERISTEMLESS genes via an upstream-conserved noncoding sequence coordinates leaf development

    PubMed Central

    Uchida, Naoyuki; Townsley, Brad; Chung, Kook-Hyun; Sinha, Neelima

    2007-01-01

    The indeterminate shoot apical meristem of plants is characterized by the expression of the Class 1 KNOTTED1-LIKE HOMEOBOX (KNOX1) genes. KNOX1 genes have been implicated in the acquisition and/or maintenance of meristematic fate. One of the earliest indicators of a switch in fate from indeterminate meristem to determinate leaf primordium is the down-regulation of KNOX1 genes orthologous to SHOOT MERISTEMLESS (STM) in Arabidopsis (hereafter called STM genes) in the initiating primordia. In simple leafed plants, this down-regulation persists during leaf formation. In compound leafed plants, however, KNOX1 gene expression is reestablished later in the developing primordia, creating an indeterminate environment for leaflet formation. Despite this knowledge, most aspects of how STM gene expression is regulated remain largely unknown. Here, we identify two evolutionarily conserved noncoding sequences within the 5′ upstream region of STM genes in both simple and compound leafed species across monocots and dicots. We show that one of these elements is involved in the regulation of the persistent repression and/or the reestablishment of STM expression in the developing leaves but is not involved in the initial down-regulation in the initiating primordia. We also show evidence that this regulation is developmentally significant for leaf formation in the pathway involving ASYMMETRIC LEAVES1/2 (AS1/2) gene expression; these genes are known to function in leaf development. Together, these findings reveal a regulatory point of leaf development mediated through a conserved, noncoding sequence in STM genes. PMID:17898165

  16. Phylogenetic analysis reveals conservation and diversification of micro RNA166 genes among diverse plant species.

    PubMed

    Barik, Suvakanta; SarkarDas, Shabari; Singh, Archita; Gautam, Vibhav; Kumar, Pramod; Majee, Manoj; Sarkar, Ananda K

    2014-01-01

    Similar to the majority of the microRNAs, mature miR166s are derived from multiple members of MIR166 genes (precursors) and regulate various aspects of plant development by negatively regulating their target genes (Class III HD-ZIP). The evolutionary conservation or functional diversification of miRNA166 family members remains elusive. Here, we show the phylogenetic relationships among MIR166 precursor and mature sequences from three diverse model plant species. Despite strong conservation, some mature miR166 sequences, such as ppt-miR166m, have undergone sequence variation. Critical sequence variation in ppt-miR166m has led to functional diversification, as it targets non-HD-ZIPIII gene transcript (s). MIR166 precursor sequences have diverged in a lineage specific manner, and both precursors and mature osa-miR166i/j are highly conserved. Interestingly, polycistronic MIR166s were present in Physcomitrella and Oryza but not in Arabidopsis. The nature of cis-regulatory motifs on the upstream promoter sequences of MIR166 genes indicates their possible contribution to the functional variation observed among miR166 species.

  17. Fibrinogen {alpha} genes: Conservation of bipartite transcripts and carboxy-terminal-extended {alpha} subunits in vertebrates

    SciTech Connect

    Fu, Y.; Cao, Y.; Hertzberg, K.M.; Grieninger, G.

    1995-11-01

    All three well-studied subunits of the clotting protein fibrinogen ({alpha}, {beta}, {gamma}) share N-terminal structural homologies, but until recently only the {beta} and {gamma} chains were recognized as having similar globular C-termini. With the discovery of an extra exon in the human fibrinogen {alpha} gene (exon VI), a minor form of the {alpha} subunit ({alpha}{sub E}) with an extended {beta}- and {gamma}-like C-terminus has been identified. In the present study, the polymerase chain reaction has been used to identify sequences that encode counterparts to {alpha}{sub E} in chicken, rabbit, rat, and baboon. The basic six-exon structure of the fibrinogen {alpha} genes is shown to be conserved among mammals and birds, as are the intron positions. Bipartite transcripts - still bearing an intron prior to the last exon - are found among the products of the various vertebrate fibrinogen {alpha} genes. The last exon represents the largest conserved segment of the gene and, in each species examined, encodes exactly 236 amino acids. The C-termini of these {alpha}{sub E} chains align without a single gap and are between 76 and 99% identical. Since the exon VI-encoded domain of {alpha}{sub E} is as well conserved as the corresponding regions of the {beta} and {gamma} chains, it follows that it is equally important and that {alpha}{sub E}-fibrinogen plays a vital, if as-yet unrecognized physiological role. 21 refs., 7 figs., 1 tab.

  18. Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate Paramecium.

    PubMed

    Catania, Francesco; Lynch, Michael

    2010-05-04

    In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa) remains a virtually unexplored issue. By screening Paramecium tetraurelia's 3' untranslated regions for 8-mers that were previously found to be preserved in mammalian 3' UTRs, we detect and characterize a motif that is distinctly conserved in the ribosomal genes of this ciliate. The motif appears to be conserved across Paramecium aurelia species but is absent from the ribosomal genes of four additional non-Paramecium species surveyed, including another ciliate, Tetrahymena thermophila. Motif-free ribosomal genes retain fewer paralogs in the genome and appear to be lost more rapidly relative to motif-containing genes. Features associated with the discovered preserved motif are consistent with this 8-mer playing a role in post-transcriptional regulation. Our observations 1) shed light on the evolution of a putative regulatory motif across large phylogenetic distances; 2) are expected to facilitate the understanding of the modulation of ribosomal genes expression in Paramecium; and 3) reveal a largely unexplored--and presumably not restricted to Paramecium--association between the presence/absence of a DNA motif and the evolutionary fate of its host genes.

  19. Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate Paramecium

    PubMed Central

    2010-01-01

    Background In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa) remains a virtually unexplored issue. Results By screening Paramecium tetraurelia's 3' untranslated regions for 8-mers that were previously found to be preserved in mammalian 3' UTRs, we detect and characterize a motif that is distinctly conserved in the ribosomal genes of this ciliate. The motif appears to be conserved across Paramecium aurelia species but is absent from the ribosomal genes of four additional non-Paramecium species surveyed, including another ciliate, Tetrahymena thermophila. Motif-free ribosomal genes retain fewer paralogs in the genome and appear to be lost more rapidly relative to motif-containing genes. Features associated with the discovered preserved motif are consistent with this 8-mer playing a role in post-transcriptional regulation. Conclusions Our observations 1) shed light on the evolution of a putative regulatory motif across large phylogenetic distances; 2) are expected to facilitate the understanding of the modulation of ribosomal genes expression in Paramecium; and 3) reveal a largely unexplored--and presumably not restricted to Paramecium--association between the presence/absence of a DNA motif and the evolutionary fate of its host genes. PMID:20441586

  20. Conserved gene clusters in bacterial genomes provide further support for the primacy of RNA

    NASA Technical Reports Server (NTRS)

    Siefert, J. L.; Martin, K. A.; Abdi, F.; Widger, W. R.; Fox, G. E.

    1997-01-01

    Five complete bacterial genome sequences have been released to the scientific community. These include four (eu)Bacteria, Haemophilus influenzae, Mycoplasma genitalium, M. pneumoniae, and Synechocystis PCC 6803, as well as one Archaeon, Methanococcus jannaschii. Features of organization shared by these genomes are likely to have arisen very early in the history of the bacteria and thus can be expected to provide further insight into the nature of early ancestors. Results of a genome comparison of these five organisms confirm earlier observations that gene order is remarkably unpreserved. There are, nevertheless, at least 16 clusters of two or more genes whose order remains the same among the four (eu)Bacteria and these are presumed to reflect conserved elements of coordinated gene expression that require gene proximity. Eight of these gene orders are essentially conserved in the Archaea as well. Many of these clusters are known to be regulated by RNA-level mechanisms in Escherichia coli, which supports the earlier suggestion that this type of regulation of gene expression may have arisen very early. We conclude that although the last common ancestor may have had a DNA genome, it likely was preceded by progenotes with an RNA genome.

  1. Conserved Fungal Genes as Potential Targets for Broad-Spectrum Antifungal Drug Discovery†

    PubMed Central

    Liu, Mengping; Healy, Matthew D.; Dougherty, Brian A.; Esposito, Kim M.; Maurice, Trina C.; Mazzucco, Charles E.; Bruccoleri, Robert E.; Davison, Daniel B.; Frosco, Marybeth; Barrett, John F.; Wang, Ying-Kai

    2006-01-01

    The discovery of novel classes of antifungal drugs depends to a certain extent on the identification of new, unexplored targets that are essential for growth of fungal pathogens. Likewise, the broad-spectrum capacity of future antifungals requires the target gene(s) to be conserved among key fungal pathogens. Using a genome comparison (or concordance) tool, we identified 240 conserved genes as candidates for potential antifungal targets in 10 fungal genomes. To facilitate the identification of essential genes in Candida albicans, we developed a repressible C. albicans MET3 (CaMET3) promoter system capable of evaluating gene essentiality on a genome-wide scale. The CaMET3 promoter was found to be highly amenable to controlled gene expression, a prerequisite for use in target-based whole-cell screening. When the expression of the known antifungal target C. albicans ERG1 was reduced via down-regulation of the CaMET3 promoter, the CaERG1 conditional mutant strain became hypersensitive, specifically to its inhibitor, terbinafine. Furthermore, parallel screening against a small compound library using the CaERG1 conditional mutant under normal and repressed conditions uncovered several hypersensitive compound hits. This work therefore demonstrates a streamlined process for proceeding from selection and validation of candidate antifungal targets to screening for specific inhibitors. PMID:16607011

  2. Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein motif with a Drosophila omb gene

    SciTech Connect

    Campbell, C.; Goodrich, K.; Casey, G.; Beatty, B.

    1995-07-20

    We have identified and cloned a human gene (TBX2) that exhibits strong sequence homology within a putative DNA binding domain to the drosophila optomotor-blind (omb) gene and lesser homology to the DNA binding domain of the murine brachyury or T gene. Unlike omb, which is expressed in neural tissue, or T, which is not expressed in adult animals, TBX2 is expressed primarily in adult in kidney, lung, and placenta as multiple transcripts of between {approximately} 2 and 4 kb. At least part of this transcript heterogenity appears to be due to alternative polyadenylation. This is the first reported human member of a new family of highly evolutionarily conserved DNA binding proteins, the Tbx or T-box proteins. The human gene has been mapped by somatic cell hybrid mapping and chromosomal in situ hybridization to chromosome 17q23, a region frequently altered in ovarian carcinomas. 19 refs., 6 figs.

  3. Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats - altered levels of gene expression, enzymes and hormones.

    PubMed

    Kumar, Vikas; Kural, Mool Raj; Pereira, B M J; Roy, Partha

    2008-12-01

    Mentha spicata Labiatae, commonly known as spearmint, can be used for various kinds of illnesses in herbal medicines and food industries. One of the prominent functions of this plant extract is its anti-androgenic activity. The present study investigated the probable correlation between oxidative stress in hypothalamic region and anti-androgenic action of this plant's aqueous extract on rats. Decreased activities of enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in hypothalamus of treated rats indicated spearmint induced oxidative stress. Further RT-PCR and immunoblot analysis demonstrated the decreased expression of some of the steroidogenic enzymes, cytochrome P450scc, cytochrome P450C17, 3beta-Hydroxysteroid dehydrogenase (3beta-HSD), 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) and other related proteins like, steroidogenic acute regulatory protein, androgen receptor and scavenger receptor class B-1. Further, in vitro enzyme assays demonstrated depressed activities of testicular 3beta-HSD and 17beta-HSD enzymes. Histopathology indicated a decreased sperm density in cauda epididymis and degeneration of ductus deference. Our study suggested that spearmint probably induced oxidative stress in hypothalamus resulting in decreased synthesis of LH and FSH which in turn down-regulated the production of testicular testosterone through the disruption of a number of intermediate cascades.

  4. Conservation, Divergence, and Genome-Wide Distribution of PAL and POX A Gene Families in Plants

    PubMed Central

    Rawal, H. C.; Singh, N. K.; Sharma, T. R.

    2013-01-01

    Genome-wide identification and phylogenetic and syntenic comparison were performed for the genes responsible for phenylalanine ammonia lyase (PAL) and peroxidase A (POX A) enzymes in nine plant species representing very diverse groups like legumes (Glycine max and Medicago truncatula), fruits (Vitis vinifera), cereals (Sorghum bicolor, Zea mays, and Oryza sativa), trees (Populus trichocarpa), and model dicot (Arabidopsis thaliana) and monocot (Brachypodium distachyon) species. A total of 87 and 1045 genes in PAL and POX A gene families, respectively, have been identified in these species. The phylogenetic and syntenic comparison along with motif distributions shows a high degree of conservation of PAL genes, suggesting that these genes may predate monocot/eudicot divergence. The POX A family genes, present in clusters at the subtelomeric regions of chromosomes, might be evolving and expanding with higher rate than the PAL gene family. Our analysis showed that during the expansion of POX A gene family, many groups and subgroups have evolved, resulting in a high level of functional divergence among monocots and dicots. These results will act as a first step toward the understanding of monocot/eudicot evolution and functional characterization of these gene families in the future. PMID:23671845

  5. Conservation of DNA curvature signals in regulatory regions of prokaryotic genes

    PubMed Central

    Jáuregui, Ruy; Abreu-Goodger, Cei; Moreno-Hagelsieb, Gabriel; Collado-Vides, Julio; Merino, Enrique

    2003-01-01

    DNA curvature plays a well-characterized role in many transcriptional regulation mechanisms. We present evidence for the conservation of curvature signals in putative regulatory regions of several archaeal and eubacterial genomes. Genes with highly curved upstream regions were identified in orthologous groups, based on the annotations of the Cluster of Orthologous Groups of proteins (COG) database. COGs possessing a significant number of genes with curvature signals were analyzed, and conserved properties were found in several cases. Curvature signals related to regulatory sites, previously described in single organisms, were located in a broad spectrum of bacterial genomes. Global regulatory proteins, such as HU, IHF and FIS, known to bind to curved DNA and to be autoregulated, were found to present conserved DNA curvature signals in their regulatory regions, emphasizing the fact that structural parameters of the DNA molecule are conserved elements in the process of transcriptional regulation of some systems. It is currently an open question whether these diverse systems are part of an integrated global regulatory response in different microorganisms. PMID:14627810

  6. Phylogenetic conservation of immunoglobulin heavy chains: direct comparison of hamster and mouse Cmu genes.

    PubMed

    McGuire, K L; Duncan, W R; Tucker, P W

    1985-08-12

    We have analyzed the JH-Cmu locus of the Syrian hamster by DNA cloning and sequencing. The single Cmu gene is highly homologous to that of the mouse. The hamster equivalents of the JH and switch (S) recombination regions are arranged as in the mouse, but surprisingly are not highly conserved. Also unlike its close murine relative, the Smu regions among inbred hamster strains are not polymorphic. The complete nucleotide sequence of hamster and mouse Cmu genes have been compared to partial Cmu sequences of other species. Conservation within a portion of the 3' untranslated region may signify functional requirements for 3' end processing. Mutational frequencies within exons and introns of hamster and mouse do not support the theory that the rate of DNA transitions to transversions decreases with evolutionary distance.

  7. Primary testicular lymphoma.

    PubMed Central

    Vural, Filiz; Cagirgan, Seckin; Saydam, Guray; Hekimgil, Mine; Soyer, Nur Akad; Tombuloglu, Murat

    2007-01-01

    We evaluated clinical features, management and survival of 12 patients with primary testicular non-Hodgkin's lymphoma presented to our hematology unit between January 1992 and July 2006, retrospectively. The median age of patients was 47 years at presentation (range 29-78 years) and > 80% of them were < 50 years old. In the majority of cases, orchidectomy was performed as diagnostic and first-line therapeutic procedures. Dominant histological subtype was diffuse large B-cell non-Hodgkin's lymphoma. Seven patients out of 12 (58%) were Ann Arbor stages I and II, and the remaining five patients (42%) were stages III and IV. All the patients received doxorubicin-based chemotherapy and achieved complete remission. The addition of rituximab and central nervous system prophylaxis with intrathecal combined chemotherapy containing methotrexate, cytarabine and dexametasone were applied to three patients who were recently admitted. The rate of relapse was 8% and progression-free survival (PFS) at 10 years was 88%. Median duration of response was 84 months (range 14-173 months), median 97.5 months of follow-up. All patients are alive and in case remission. Because of the spreading nature and relapse probability at different sites, including central nervous system and contralateral testis, systemic treatment with doxorubicin-based chemotherapy with or without prophylaxis for contralateral testis and the central nervous system seems to improve the outcome of primary testicular lymphoma. PMID:18020104

  8. A Conserved Structural Signature of the Homeobox Coding DNA in HOX genes.

    PubMed

    Fongang, Bernard; Kong, Fanping; Negi, Surendra; Braun, Werner; Kudlicki, Andrzej

    2016-10-14

    The homeobox encodes a DNA-binding domain found in transcription factors regulating key developmental processes. The most notable examples of homeobox containing genes are the Hox genes, arranged on chromosomes in the same order as their expression domains along the body axis. The mechanisms responsible for the synchronous regulation of Hox genes and the molecular function of their colinearity remain unknown. Here we report the discovery of a conserved structural signature of the 180-base pair DNA fragment comprising the homeobox. We demonstrate that the homeobox DNA has a characteristic 3-base-pair periodicity in the hydroxyl radical cleavage pattern. This periodic pattern is significant in most of the 39 mammalian Hox genes and in other homeobox-containing transcription factors. The signature is present in segmented bilaterian animals as evolutionarily distant as humans and flies. It remains conserved despite the fact that it would be disrupted by synonymous mutations, which raises the possibility of evolutionary selective pressure acting on the structure of the coding DNA. The homeobox coding DNA may therefore have a secondary function, possibly as a regulatory element. The existence of such element may have important consequences for understanding how these genes are regulated.

  9. A Conserved Structural Signature of the Homeobox Coding DNA in HOX genes

    PubMed Central

    Fongang, Bernard; Kong, Fanping; Negi, Surendra; Braun, Werner; Kudlicki, Andrzej

    2016-01-01

    The homeobox encodes a DNA-binding domain found in transcription factors regulating key developmental processes. The most notable examples of homeobox containing genes are the Hox genes, arranged on chromosomes in the same order as their expression domains along the body axis. The mechanisms responsible for the synchronous regulation of Hox genes and the molecular function of their colinearity remain unknown. Here we report the discovery of a conserved structural signature of the 180-base pair DNA fragment comprising the homeobox. We demonstrate that the homeobox DNA has a characteristic 3-base-pair periodicity in the hydroxyl radical cleavage pattern. This periodic pattern is significant in most of the 39 mammalian Hox genes and in other homeobox-containing transcription factors. The signature is present in segmented bilaterian animals as evolutionarily distant as humans and flies. It remains conserved despite the fact that it would be disrupted by synonymous mutations, which raises the possibility of evolutionary selective pressure acting on the structure of the coding DNA. The homeobox coding DNA may therefore have a secondary function, possibly as a regulatory element. The existence of such element may have important consequences for understanding how these genes are regulated. PMID:27739488

  10. Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis.

    PubMed

    Yang, Hongwen

    2013-06-01

    L-gulono-gamma-lactone oxidase (GULO) catalyzes the final step in vertebrate vitamin C biosynthesis. Vitamin C-incapable vertebrates lack the GULO gene. Gene structure and phylogenetic analyses showed that vertebrate GULO genes are 64-95% identical at the amino acid level and consist of 11 conserved exons. GULO pseudogenes have multiple indel mutations and premature stop codons in higher primates, guinea pigs, and some bats. No GULO-like sequences were identified in teleost fishes. During animal GULO evolution, exon F was subdivided into F1 and F2. Additional GULO retropseudogenes were identified in dogs, cats, and giant pandas. GULO-flanking genome regions acquired frequent segment translocations and inversions during vertebrate evolution. Purifying selection was detected across vertebrate GULO genes (d(N)/d(S) = 0.069), except for some positively selected sites identified in sharks and frogs. These positive sites demonstrated little functional significance when mapped onto the three-dimensional GULO protein structure. Vertebrate GULO genes are conserved except for those that are lost.

  11. Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

    PubMed Central

    Fuse, Yuji; Tamaoki, Junya; Akiyama, Shin-ichi; Muratani, Masafumi

    2016-01-01

    The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7) and 2 enzymes involved in glucose metabolism (pgd and fbp1a) were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates. PMID:28116036

  12. Regulation of the segmentation gene fushi tarazu has been functionally conserved in Drosophila.

    PubMed Central

    Maier, D; Preiss, A; Powell, J R

    1990-01-01

    An evolutionary approach was applied to identify elements involved in the regulation of the segmentation gene fushi tarazu (ftz) by comparing the Drosophila melanogaster ftz gene with its Drosophila hydei homologue. The overall organization of the ftz gene is very similar in both species. Surprisingly, ftz proved to be inverted in the ANT-C of D. hydei with respect to D. melanogaster. Strong homologies extend over the entire 6 kb of the ftz upstream region with the best match in the 'upstream element'. We identified several highly conserved boxes embedded in unrelated sequences that correspond extremely well to two germ layer specific enhancers in the upstream element. Transformation experiments revealed that D. hydei ftz gene products can restore D. melanogaster ftz function and, furthermore, that trans-acting factors from D. melanogaster recognize and control D. hydei ftz regulatory elements. These findings indicate a conservation of the entire regulatory network among segmentation genes for several millions of years during the evolution of Drosophila. Images Fig. 2. Fig. 6. PMID:2174353

  13. Comparative genomic analysis reveals the evolutionary conservation of Pax gene family.

    PubMed

    Wang, Wei; Zhong, Jing; Wang, Yi-Quan

    2010-01-01

    The Pax gene family encodes a group of transcription factors whose evolution has accompanied the major morphological and functional innovations of vertebrate species. The evolutionary conservation throughout diverse lineages of metazoan and the functional importance in development rendered Pax family an ideal system to address the relationship inside Chordata phylum. In the present study, we sequenced and annotated four genomic regions containing Chinese amphioxus (Branchiostoma belcheri) Pax genes, and retrieved homologous sequences from public database. In comparison with vertebrate homologues, the predicted amphioxus Pax proteins display high sequence conservation. Evidences from the molecular phylogenetic studies and gene organization analyses supports cephalochordates have a much closer relationship to vertebrates than that between tunicates and vertebrates, contrasting to urochordate relatives hypothesis proposed by several latest studies. Analysis of phylogenetic topology derived from concatenated subfamily datasets uncovered a potential statistical bias of supermatrix approach. Furthermore, we deduced an evolutionary scenario of Pax gene family. This scenario provided a plausible explanation for the origin and dynamics of the Pax gene members.

  14. CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation.

    PubMed

    Nikulova, Anna A; Favorov, Alexander V; Sutormin, Roman A; Makeev, Vsevolod J; Mironov, Andrey A

    2012-07-01

    Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory 'grammar', or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila.

  15. Functional conservation of the fruitless male sex-determination gene across 250 Myr of insect evolution.

    PubMed

    Gailey, Donald A; Billeter, Jean-Christophe; Liu, Jim H; Bauzon, Frederick; Allendorfer, Jane B; Goodwin, Stephen F

    2006-03-01

    Male sexual behavior in the fruit fly Drosophila melanogaster is regulated by fruitless (fru), a sex-determination gene specifying the synthesis of BTB-Zn finger proteins that likely function as male-specific transcriptional regulators. Expression of fru in the nervous system specifies male sexual behavior and the muscle of Lawrence (MOL), an abdominal muscle that develops in males but not in females. We have isolated the fru ortholog from the malaria mosquito Anopheles gambiae and show the gene's conserved genomic structure. We demonstrate that male-specific mosquito fru protein isoforms arise by conserved mechanisms of sex-specifically activated and alternative exon splicing. A male-determining function of mosquito fru is revealed by ectopic expression of the male mosquito isoform FRUMC in fruit flies; this results in MOL development in both fru-mutant males and fru+ females who otherwise develop no MOL. In parallel, we provide evidence of a unique feature of muscle differentiation within the fifth abdominal segment of male mosquitoes that strongly resembles the fruit fly MOL. Given these conserved features within the context of 250 Myr of evolutionary divergence between Drosophila and Anopheles, we hypothesize that fru is the prototypic gene of male sexual behavior among dipteran insects.

  16. Making teeth to order: conserved genes reveal an ancient molecular pattern in paddlefish (Actinopterygii)

    PubMed Central

    Smith, Moya M.; Johanson, Zerina; Butts, Thomas; Ericsson, Rolf; Modrell, Melinda; Tulenko, Frank J.; Davis, Marcus C.; Fraser, Gareth J.

    2015-01-01

    Ray-finned fishes (Actinopterygii) are the dominant vertebrate group today (+30 000 species, predominantly teleosts), with great morphological diversity, including their dentitions. How dental morphological variation evolved is best addressed by considering a range of taxa across actinopterygian phylogeny; here we examine the dentition of Polyodon spathula (American paddlefish), assigned to the basal group Acipenseriformes. Although teeth are present and functional in young individuals of Polyodon, they are completely absent in adults. Our current understanding of developmental genes operating in the dentition is primarily restricted to teleosts; we show that shh and bmp4, as highly conserved epithelial and mesenchymal genes for gnathostome tooth development, are similarly expressed at Polyodon tooth loci, thus extending this conserved developmental pattern within the Actinopterygii. These genes map spatio-temporal tooth initiation in Polyodon larvae and provide new data in both oral and pharyngeal tooth sites. Variation in cellular intensity of shh maps timing of tooth morphogenesis, revealing a second odontogenic wave as alternate sites within tooth rows, a dental pattern also present in more derived actinopterygians. Developmental timing for each tooth field in Polyodon follows a gradient, from rostral to caudal and ventral to dorsal, repeated during subsequent loss of teeth. The transitory Polyodon dentition is modified by cessation of tooth addition and loss. As such, Polyodon represents a basal actinopterygian model for the evolution of developmental novelty: initial conservation, followed by tooth loss, accommodating the adult trophic modification to filter-feeding. PMID:25788604

  17. Identification of a conserved sequence in the non-coding regions of many human genes

    SciTech Connect

    Donehower, L.A.; Slagle, B.L.; Wilde, M.; Darlington, G.; Butel, J.S. )

    1989-01-25

    The authors have analyzed a sequence of approximately 70 base pairs (bp) that shows a high degree of similarity to sequences present in the non-coding regions of a number of human and other mammalian genes. The sequence was discovered in a fragment of human genomic DNA adjacent to an integrated hepatitis B virus genome in cells derived from human hepatocellular carcinoma tissue. When one of the viral flanking sequences was compared to nucleotide sequences in GenBank, more than thirty human genes were identified that contained a similar sequence in their non-coding regions. This element was highly conserved at the same position within the corresponding human and mouse genes for myoglobin and N-myc, indicating evolutionary conservation and possible functional importance. Preliminary DNase I footprinting data suggested that the element or its adjacent sequences may bind nuclear factors to generate specific DNase I hypersensitive sites. The size, structure, and evolutionary conservation of this sequence indicates that it is distinct from other types of short interspersed repetitive elements. It is possible that the element may have a cis-acting functional role in the genome.

  18. Gene expression suggests conserved mechanisms patterning the heads of insects and myriapods.

    PubMed

    Janssen, Ralf; Budd, Graham E; Damen, Wim G M

    2011-09-01

    Segmentation, i.e. the subdivision of the body into serially homologous units, is one of the hallmarks of the arthropods. Arthropod segmentation is best understood in the fly Drosophila melanogaster. But different from the situation in most arthropods in this species all segments are formed from the early blastoderm (so called long-germ developmental mode). In most other arthropods only the anterior segments are formed in a similar way (so called short-germ developmental mode). Posterior segments are added one at a time or in pairs of two from a posterior segment addition zone. The segmentation mechanisms are not universally conserved among arthropods and only little is known about the genetic patterning of the anterior segments. Here we present the expression patterns of the insect head patterning gene orthologs hunchback (hb), orthodenticle (otd), buttonhead-like (btdl), collier (col), cap-n-collar (cnc) and crocodile (croc), and the trunk gap gene Krüppel (Kr) in the myriapod Glomeris marginata. Conserved expression of these genes in insects and a myriapod suggests that the anterior segmentation system may be conserved in at least these two classes of arthropods. This finding implies that the anterior patterning mechanism already existed in the last common ancestor of insects and myriapods.

  19. Evolutionary analysis of the mammalian M1 aminopeptidases reveals conserved exon structure and gene death.

    PubMed

    Maynard, Karen Beasley; Smith, Shannon A; Davis, Anthony C; Trivette, Andrew; Seipelt-Thiemann, Rebecca L

    2014-11-15

    The members of the M1 aminopeptidase family share conserved domains, yet show functional divergence within the family as a whole. In order to better understand this family, this study analyzed the mammalian members in depth at exon, gene, and protein levels. The twelve human members, eleven rat members, and eleven mouse members were first analyzed in multiple alignments to visualize both reported and unreported conserved domains. Phylogenetic trees were then generated for humans, rats, mice, and all mammals to determine how closely related the homologs were and to gain insight to the divergence in the family members. This produced three groups with similarity within the family. Next, a synteny study was completed to determine the present locations of the genes and changes that had occurred. It became apparent that gene death likely resulted in the lack of one member in mouse and rat. Finally, an in-depth analysis of the exon structure revealed that nine members of the human family and eight in mouse, are highly conserved within the exon structure. Taken together, these results indicate that the M1 aminopeptidase family is a divergent family with three subgroups and that genetic evidence mirrors categorization of the family by enzymatic function.

  20. Phylogenetic Resolution of Deep Eukaryotic and Fungal Relationships Using Highly Conserved Low-Copy Nuclear Genes.

    PubMed

    Ren, Ren; Sun, Yazhou; Zhao, Yue; Geiser, David; Ma, Hong; Zhou, Xiaofan

    2016-09-11

    A comprehensive and reliable eukaryotic tree of life is important for many aspects of biological studies from comparative developmental and physiological analyses to translational medicine and agriculture. Both gene-rich and taxon-rich approaches are effective strategies to improve phylogenetic accuracy and are greatly facilitated by marker genes that are universally distributed, well conserved, and orthologous among divergent eukaryotes. In this article, we report the identification of 943 low-copy eukaryotic genes and we show that many of these genes are promising tools in resolving eukaryotic phylogenies, despite the challenges of determining deep eukaryotic relationships. As a case study, we demonstrate that smaller subsets of ∼20 and 52 genes could resolve controversial relationships among widely divergent taxa and provide strong support for deep relationships such as the monophyly and branching order of several eukaryotic supergroups. In addition, the use of these genes resulted in fungal phylogenies that are congruent with previous phylogenomic studies that used much larger datasets, and successfully resolved several difficult relationships (e.g., forming a highly supported clade with Microsporidia, Mitosporidium and Rozella sister to other fungi). We propose that these genes are excellent for both gene-rich and taxon-rich analyses and can be applied at multiple taxonomic levels and facilitate a more complete understanding of the eukaryotic tree of life. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. rbcS genes in Solanum tuberosum: conservation of transit peptide and exon shuffling during evolution.

    PubMed Central

    Wolter, F P; Fritz, C C; Willmitzer, L; Schell, J; Schreier, P H

    1988-01-01

    Five genes of the rbcS gene family of Solanum tuberosum (potato) were studied. One of these is a cDNA clone; the other four are located on two genomic clones representing two different chromosomal loci containing one (locus 1) and three genes (locus 2), respectively. The intron/exon structure of the three genes in locus 2 is highly conserved with respect to size and position. These genes contain two introns, whereas the gene from locus 1 contains three introns. Although in most cases the amino acid sequences in the transit peptide part of different rbcS genes from the same species varied considerably more than the corresponding mature amino acid sequences, one exception found in tomato and potato indicates that the transit peptide of rbcS could have a special function. A comparison of the rbcS genes of higher plants with those of prokaryotes offers suggestive evidence that introns first served as spacer material in the process of exon shuffling and then were removed stepwise during the evolution of higher plants. PMID:3422467

  2. Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes.

    PubMed

    Black, W C; Roehrdanz, R L

    1998-12-01

    The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are basal members of Ixodidae and have the same gene order as Limulus polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA, tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln) have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes. The tRNA(Cys) gene has translocated between the control region and the tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region is duplicated, and both copies undergo concerted evolution. Primers that flank these rearrangements confirm that this gene order is conserved in all metastriate ticks examined. Correspondence analysis of amino acid and codon use in the two ticks and in nine other arthropod mitochondrial genomes indicate a strong bias in R. sanguineus towards amino acids encoded by AT-rich codons.

  3. Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals

    PubMed Central

    Nelander, Sven; Larsson, Erik; Kristiansson, Erik; Månsson, Robert; Nerman, Olle; Sigvardsson, Mikael; Mostad, Petter; Lindahl, Per

    2005-01-01

    Background The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation. Results In a screen that covered ~40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in ~10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in ~30% of all kidney specific genes respectively. The results are publicly available at . Conclusion 21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design. PMID:15882449

  4. A highly conserved NB-LRR encoding gene cluster effective against Setosphaeria turcica in sorghum

    PubMed Central

    2011-01-01

    Background The fungal pathogen Setosphaeria turcica causes turcicum or northern leaf blight disease on maize, sorghum and related grasses. A prevalent foliar disease found worldwide where the two host crops, maize and sorghum are grown. The aim of the present study was to find genes controlling the host defense response to this devastating plant pathogen. A cDNA-AFLP approach was taken to identify candidate sequences, which functions were further validated via virus induced gene silencing (VIGS), and real-time PCR analysis. Phylogenetic analysis was performed to address evolutionary events. Results cDNA-AFLP analysis was run on susceptible and resistant sorghum and maize genotypes to identify resistance-related sequences. One CC-NB-LRR encoding gene GRMZM2G005347 was found among the up-regulated maize transcripts after fungal challenge. The new plant resistance gene was designated as St referring to S. turcica. Genome sequence comparison revealed that the CC-NB-LRR encoding St genes are located on chromosome 2 in maize, and on chromosome 5 in sorghum. The six St sorghum genes reside in three pairs in one locus. When the sorghum St genes were silenced via VIGS, the resistance was clearly compromised, an observation that was supported by real-time PCR. Database searches and phylogenetic analysis suggest that the St genes have a common ancestor present before the grass subfamily split 50-70 million years ago. Today, 6 genes are present in sorghum, 9 in rice and foxtail millet, respectively, 3 in maize and 4 in Brachypodium distachyon. The St gene homologs have all highly conserved sequences, and commonly reside as gene pairs in the grass genomes. Conclusions Resistance genes to S. turcica, with a CC-NB-LRR protein domain architecture, have been found in maize and sorghum. VIGS analysis revealed their importance in the surveillance to S. turcica in sorghum. The St genes are highly conserved in sorghum, rice, foxtail millet, maize and Brachypodium, suggesting an

  5. Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservation.

    PubMed

    Botta, A; Lindsay, E A; Jurecic, V; Baldini, A

    1997-12-01

    We have constructed a comparative map in mouse of the critical region of human 22q11 deleted in DiGeorge (DGS) and Velocardiofacial (VCFS) syndromes. The map includes 11 genes potentially haploinsufficient in these deletion syndromes. We have localized all the conserved genes to mouse Chromosome (Chr) 16, bands B1-B3. The determination of gene order shows the presence of two regions (distal and proximal), containing two groups of conserved genes. The gene order in the two regions is not completely conserved; only in the proximal group is the gene order identical to human. In the distal group the gene order is inverted. These two regions are separated by a DNA segment containing at least one gene which, in the human DGS region, is the most proximal of the known deleted genes. In addition, the gene order within the distal group of genes is inverted relative to the human gene order. Furthermore, a clathrin heavy chain-like gene was not found in the mouse genome by DNA hybridization, indicating that there is an inconsistent level of gene conservation in the region. These and other independent data obtained in our laboratory clearly show a complex evolutionary history of the DGS-VCFS region. Our data provide a framework for the development of a mouse model for the 22q11 deletion with chromosome engineering technologies.

  6. Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

    PubMed

    Ahmed-Farid, Omar A H; Nasr, Maha; Ahmed, Rania F; Bakeer, Rofanda M

    2017-09-02

    Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2(nd)group; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological

  7. Functional conservation and diversification of class E floral homeotic genes in rice (Oryza sativa).

    PubMed

    Cui, Rongfeng; Han, Jiakun; Zhao, Suzhen; Su, Kunmei; Wu, Feng; Du, Xiaoqiu; Xu, Qijiang; Chong, Kang; Theissen, Günter; Meng, Zheng

    2010-03-01

    Mutant analyses in different eudicotyledonous flowering plants demonstrated that SEPALLATA-like MADS-box genes are required for the specification of sepals, petals, stamens and carpels, and for floral determinacy, thus defining class E floral organ identity genes. SEP-like genes encode MADS-domain transcription factors and constitute an angiosperm-specific gene clade whose members show remarkably different degrees of redundancy and sub-functionalization within eudicots. To better understand the evolutionary dynamics of SEP-like genes throughout the angiosperms we have knocked down SEP-like genes of rice (Oryza sativa), a distant relative of eudicots within the flowering plants. Plants affected in both OsMADS7 and OsMADS8 show severe phenotypes including late flowering, homeotic changes of lodicules, stamens and carpels into palea/lemma-like organs, and a loss of floral determinacy. Simultaneous knockdown of the four rice SEP-like genes OsMADS1, OsMADS5, OsMADS7 and OsMADS8, leads to homeotic transformation of all floral organs except the lemma into leaf-like organs. This mimics the phenotype observed with the sep1 sep2 sep3 sep4 quadruple mutant of Arabidopsis. Detailed analyses of the spatial and temporal mRNA expression and protein interaction patterns corresponding to the different rice SEP-like genes show strong similarities, but also gene-specific differences. These findings reveal conservation of SEP-like genes in specifying floral determinacy and organ identities since the separation of eudicots and monocots about 150 million years ago. However, they indicate also monocot-specific neo- and sub-functionalization events and hence underscore the evolutionary dynamics of SEP-like genes. Moreover, our findings corroborate the view that the lodicules of grasses are homologous to eudicot petals.

  8. Differences in global DNA methylation of testicular seminoma are not associated with changes in histone modifications, clinical prognosis, BRAF mutations or gene expression.

    PubMed

    Pedersen, Louise Holm; Nielsen, John E; Daugaard, Gedske; Hansen, Thomas V O; Rajpert-De Meyts, Ewa; Almstrup, Kristian

    2016-11-01

    Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively. A selected subset representing each level of DNA methylation and the TCam2 seminoma cell line were subsequently analysed for a range of other epigenetic marks (6 histone marks and 5-hydroxymethylcytosine), the presence of the BRAF V600E de novo mutation, differences in the transcriptome and finally correlated to the clinical outcome. We did not identify any histone marks or hydroxymethylation levels that correlated with the methylation level of the genome. Some histone marks, however, showed a great variation while others were found at the same level in all the investigated seminomas. We did not identify any tumours with the BRAF V600E mutation and transcriptome analysis revealed no significant differences between hypo- and hyper-methylated seminomas. Similarly, no obvious differences in the clinical manifestation of the patients representing hypo- or hyper-methylated seminomas were identified. The level of DNA methylation in testicular seminomas consequently seems secondary to the manifestation of the tumour phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype.

    PubMed

    Libé, Rossella; Horvath, Anelia; Vezzosi, Delphine; Fratticci, Amato; Coste, Joel; Perlemoine, Karine; Ragazzon, Bruno; Guillaud-Bataille, Marine; Groussin, Lionel; Clauser, Eric; Raffin-Sanson, Marie-Laure; Siegel, Jennifer; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Bertagna, Xavier; Bertherat, Jerome; Stratakis, Constantine A

    2011-01-01

    Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P < 0.0001). Among CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P < 0.001). A higher frequency of PDE11A sequence variants was also found in patients with large-cell calcifying Sertoli cell tumors (LCCSCT) compared with those without LCCSCT (50 vs. 10%, P = 0.0056). PDE11A variants were significantly associated with the copresence of PPNAD and LCCSCT in men: 81 vs. 20%, P < 0.004). The simultaneous inactivation of PRKAR1A and PDE11A by small inhibitory RNA led to an increase in cAMP-regulatory element-mediated transcriptional activity under basal conditions and after stimulation by forskolin. We demonstrate, in a large cohort of CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

  10. DLGP: A database for lineage-conserved and lineage-specific gene pairs in animal and plant genomes.

    PubMed

    Wang, Dapeng

    2016-01-15

    The conservation of gene organization in the genome with lineage-specificity is an invaluable resource to decipher their potential functionality with diverse selective constraints, especially in higher animals and plants. Gene pairs appear to be the minimal structure for such kind of gene clusters that tend to reside in their preferred locations, representing the distinctive genomic characteristics in single species or a given lineage. Despite gene families having been investigated in a widespread manner, the definition of gene pair families in various taxa still lacks adequate attention. To address this issue, we report DLGP (http://lcgbase.big.ac.cn/DLGP/) that stores the pre-calculated lineage-based gene pairs in currently available 134 animal and plant genomes and inspect them under the same analytical framework, bringing out a set of innovational features. First, the taxonomy or lineage has been classified into four levels such as Kingdom, Phylum, Class and Order. It adopts all-to-all comparison strategy to identify the possible conserved gene pairs in all species for each gene pair in certain species and reckon those that are conserved in over a significant proportion of species in a given lineage (e.g. Primates, Diptera or Poales) as the lineage-conserved gene pairs. Furthermore, it predicts the lineage-specific gene pairs by retaining the above-mentioned lineage-conserved gene pairs that are not conserved in any other lineages. Second, it carries out pairwise comparison for the gene pairs between two compared species and creates the table including all the conserved gene pairs and the image elucidating the conservation degree of gene pairs in chromosomal level. Third, it supplies gene order browser to extend gene pairs to gene clusters, allowing users to view the evolution dynamics in the gene context in an intuitive manner. This database will be able to facilitate the particular comparison between animals and plants, between vertebrates and arthropods, and

  11. Phylogeny of Bacterial and Archaeal Genomes Using Conserved Genes: Supertrees and Supermatrices

    PubMed Central

    Lang, Jenna Morgan; Darling, Aaron E.; Eisen, Jonathan A.

    2013-01-01

    Over 3000 microbial (bacterial and archaeal) genomes have been made publically available to date, providing an unprecedented opportunity to examine evolutionary genomic trends and offering valuable reference data for a variety of other studies such as metagenomics. The utility of these genome sequences is greatly enhanced when we have an understanding of how they are phylogenetically related to each other. Therefore, we here describe our efforts to reconstruct the phylogeny of all available bacterial and archaeal genomes. We identified 24, single-copy, ubiquitous genes suitable for this phylogenetic analysis. We used two approaches to combine the data for the 24 genes. First, we concatenated alignments of all genes into a single alignment from which a Maximum Likelihood (ML) tree was inferred using RAxML. Second, we used a relatively new approach to combining gene data, Bayesian Concordance Analysis (BCA), as implemented in the BUCKy software, in which the results of 24 single-gene phylogenetic analyses are used to generate a “primary concordance” tree. A comparison of the concatenated ML tree and the primary concordance (BUCKy) tree reveals that the two approaches give similar results, relative to a phylogenetic tree inferred from the 16S rRNA gene. After comparing the results and the methods used, we conclude that the current best approach for generating a single phylogenetic tree, suitable for use as a reference phylogeny for comparative analyses, is to perform a maximum likelihood analysis of a concatenated alignment of conserved, single-copy genes. PMID:23638103

  12. Role of Conserved Non-Coding Regulatory Elements in LMW Glutenin Gene Expression

    PubMed Central

    Juhász, Angéla; Makai, Szabolcs; Sebestyén, Endre; Tamás, László; Balázs, Ervin

    2011-01-01

    Transcriptional regulation of LMW glutenin genes were investigated in-silico, using publicly available gene sequences and expression data. Genes were grouped into different LMW glutenin types and their promoter profiles were determined using cis-acting regulatory elements databases and published results. The various cis-acting elements belong to some conserved non-coding regulatory regions (CREs) and might act in two different ways. There are elements, such as GCN4 motifs found in the long endosperm box that could serve as key factors in tissue-specific expression. Some other elements, such as the AACA/TA motifs or the individual prolamin box variants, might modulate the level of expression. Based on the promoter sequences and expression characteristic LMW glutenin genes might be transcribed following two different mechanisms. Most of the s- and i-type genes show a continuously increasing expression pattern. The m-type genes, however, demonstrate normal distribution in their expression profiles. Differences observed in their expression could be related to the differences found in their promoter sequences. Polymorphisms in the number and combination of cis-acting elements in their promoter regions can be of crucial importance in the diverse levels of production of single LMW glutenin gene types. PMID:22242127

  13. Functional conservation and diversification of the soybean maturity gene E1 and its homologs in legumes

    PubMed Central

    Zhang, Xingzheng; Zhai, Hong; Wang, Yaying; Tian, Xiaojie; Zhang, Yupeng; Wu, Hongyan; Lü, Shixiang; Yang, Guang; Li, Yuqiu; Wang, Lu; Hu, Bo; Bu, Qingyun; Xia, Zhengjun

    2016-01-01

    Gene regulatory networks involved in flowering time and photoperiodic responses in legumes remain unknown. Although the major maturity gene E1 has been successfully deciphered in soybean, knowledge on the functional conservation of this gene is limited to a certain extent to E1 homologs in legumes. The ectopic expression of Phvul.009G204600 (PvE1L), an E1 homolog from common bean, delayed the onset of flowering in soybean. By contrast, the ectopic expression of Medtr2g058520 (MtE1L) from Medicago truncatula did not affect the flowering of soybean. Characterization of the late-flowering mte1l mutant indicated that MtE1L promoted flowering in Medicago truncatula. Moreover, all transgenic E1, PvE1L and MtE1L soybean lines exhibited phenotypic changes in terms of plant height. Transgenic E1 or PvE1L plants were taller than the wild-type, whereas transgenic MtE1L plants produced dwarf phenotype with few nodes and short internode. Thus, functional conservation and diversification of E1 family genes from legumes in the regulation of flowering and plant growth may be associated with lineage specification and genomic duplication. PMID:27405888

  14. A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells

    PubMed Central

    Cantu', Claudio; Grande, Vito; Alborelli, Ilaria; Cassinelli, Letizia; Cantu’, Ileana; Colzani, Maria Teresa; Ierardi, Rossella; Ronzoni, Luisa; Cappellini, Maria Domenica; Ferrari, Giuliana; Ottolenghi, Sergio; Ronchi, Antonella

    2011-01-01

    The Sox6 transcription factor plays critical roles in various cell types, including erythroid cells. Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes. To identify new Sox6 target genes in erythroid cells, we used the known repressive double Sox6 consensus within the εy-globin promoter to perform a bioinformatic genome-wide search for similar, evolutionarily conserved motifs located within genes whose expression changes during erythropoiesis. We found a highly conserved Sox6 consensus within the Sox6 human gene promoter itself. This sequence is bound by Sox6 in vitro and in vivo, and mediates transcriptional repression in transient transfections in human erythroleukemic K562 cells and in primary erythroblasts. The binding of a lentiviral transduced Sox6FLAG protein to the endogenous Sox6 promoter is accompanied, in erythroid cells, by strong downregulation of the endogenous Sox6 transcript and by decreased in vivo chromatin accessibility of this region to the PstI restriction enzyme. These observations suggest that the negative Sox6 autoregulation, mediated by the double Sox6 binding site within its own promoter, may be relevant to control the Sox6 transcriptional downregulation that we observe in human erythroid cultures and in mouse bone marrow cells in late erythroid maturation. PMID:20852263

  15. Transfer RNA gene arrangement and codon usage in vertebrate mitochondrial genomes: a new insight into gene order conservation

    PubMed Central

    2010-01-01

    Background Mitochondrial (mt) gene arrangement has been highly conserved among vertebrates from jawless fishes to mammals for more than 500 million years. It remains unclear, however, whether such long-term persistence is a consequence of some constraints on the gene order. Results Based on the analysis of codon usage and tRNA gene positions, we suggest that tRNA gene order of the typical vertebrate mt-genomes may be important for their translational efficiency. The vertebrate mt-genome encodes 2 rRNA, 22 tRNA, and 13 transmembrane proteins consisting mainly of hydrophobic domains. We found that the tRNA genes specifying the hydrophobic residues were positioned close to the control region (CR), where the transcription efficiency is estimated to be relatively high. Using 47 vertebrate mt-genome sequences representing jawless fishes to mammals, we further found a correlation between codon usage and tRNA gene positions, implying that highly-used tRNA genes are located close to the CR. In addition, an analysis considering the asymmetric nature of mtDNA replication suggested that the tRNA loci that remain in single-strand for a longer time tend to have more guanine and thymine not suffering deamination mutations in their anticodon sites. Conclusions Our analyses imply the existence of translational constraint acting on the vertebrate mt-gene arrangement. Such translational constraint, together with the deamination-related constraint, may have contributed to long-term maintenance of gene order. PMID:20723209

  16. Intracisternal A-particle genes in Mus musculus: a conserved family of retrovirus-like elements.

    PubMed

    Kuff, E L; Smith, L A; Lueders, K K

    1981-03-01

    The structural organization of intracisternal A-particle genes has been studied, using isolates from a mouse gene library in lambda phage Charon 4A. The predominant gene form among the isolates was 7.3 kilobases (kb) in length. R-loops between the 7-kb (35S) A-particle genomic ribonucleic acid and several of these genes were colinear, with no visible evidence of intervening deoxyribonucleic acid sequences. One recombinant was found with an A-particle gene that contained a 1.7-kb deletion. Using the deletion as a reference, the deoxyribonucleic acid and ribonucleic acid homology regions were localized with respect to one another and to the restriction map: the 5' terminus of the ribonucleic acid was several hundred base pairs within the 5' end of the deoxyribonucleic acid homology region. Restriction endonuclease fragments encompassing the 5' and 3' regions of one 7.3-kb gene were separately subcloned into pBR322. Heteroduplexes between the two subclones revealed an approximately 300-base pair segment of terminally redundant sequences. The cloned 3' fragment hybridized with restriction fragments from the 5' end of several other A-particle genes, demonstrating the presence of common (though not necessarily identical) terminally repeated sequences. A-particle genes varied in the occurrence of specific restriction sites at characteristic internal loci. However, heteroduplexes between several variant 7.3-kb genes showed continuous homology regions even when spread under stringent hybridization conditions. The relative abundance of restriction site variants was highly conserved in 12 laboratory strains of Mus musculus, in embryonic and adult tissues of a single inbred strain, and in the SC-1 cell line of feral mouse origin, but appeared to differ in a feral Japanese substrain, Mus musculus molossinus. Some evidence suggests that subsets of A-particle genes may have similar flanking sequences. The results are discussed in terms of the evolution of this multigene family.

  17. Evolutionary analysis of multidrug resistance genes in fungi - impact of gene duplication and family conservation.

    PubMed

    Gossani, Cristiani; Bellieny-Rabelo, Daniel; Venancio, Thiago M

    2014-11-01

    Although the emergence of bacterial drug resistance is of great concern to the scientific community, few studies have evaluated this phenomenon systematically in fungi by using genome-wide datasets. In the present study, we assembled a large compendium of Saccharomyces cerevisiae chemical genetic data to study the evolution of multidrug resistance genes (MDRs) in the fungal lineage. We found that MDRs typically emerge in widely conserved families, most of which containing homologs from pathogenic fungi, such as Candida albicans and Coccidioides immitis, which could favor the evolution of drug resistance in those species. By integrating data from chemical genetics with protein family conservation, genetic and protein interactions, we found that gene families rarely have more than one MDR, indicating that paralogs evolve asymmetrically with regard to multidrug resistance roles. Furthermore, MDRs have more genetic and protein interaction partners than non-MDRs, supporting their participation in complex biochemical systems underlying the tolerance to multiple bioactive molecules. MDRs share more chemical genetic interactions with other MDRs than with non-MDRs, regardless of their evolutionary affinity. These results suggest the existence of an intricate system involved in the global drug tolerance phenotypes. Finally, MDRs are more likely to be hit repeatedly by mutations in laboratory evolution experiments, indicating that they have great adaptive potential. The results presented here not only reveal the main genomic features underlying the evolution of MDRs, but also shed light on the gene families from which drug resistance is more likely to emerge in fungi.

  18. Gene regulatory network plasticity predates a switch in function of a conserved transcription regulator.

    PubMed

    Nocedal, Isabel; Mancera, Eugenio; Johnson, Alexander D

    2017-03-22

    The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number of connections needed to form a novel network arise over evolutionary time. Here, we address this question using the network controlled by the fungal transcription regulator Ndt80. This conserved protein has undergone a dramatic switch in function-from an ancestral role regulating sporulation to a derived role regulating biofilm formation. This switch in function corresponded to a large-scale rewiring of the genes regulated by Ndt80. However, we demonstrate that the Ndt80-target gene connections were undergoing extensive rewiring prior to the switch in Ndt80's regulatory function. We propose that extensive drift in the Ndt80 regulon allowed for the exploration of alternative network structures without a loss of ancestral function, thereby facilitating the formation of a network with a new function.

  19. [Treatment of testicular cancer].

    PubMed

    Droz, Jean-Pierre; Boyle, Helen; Culine, Stéphane; Fizazi, Karim; Fléchon, Aude; Massard, Christophe

    2013-12-01

    Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since the late 1970s, disseminated GCT have been a paradigm for curable metastatic cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy followed by surgical resection of residual masses. Patients' prognosis is currently assessed using the International Germ-Cell Consensus Classification (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of patients still do not achieve cure after first-line cisplatin-based chemotherapy, and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical stage I testicular cancer is the most common presentation and different strategies are proposed: adjuvant therapies, surgery or surveillance. During the last three decades, clinical trials and strong international collaborations lead to the development of a consensus in the management of GCTs.

  20. Micropsia and testicular retractions.

    PubMed

    Myers, W A

    1977-01-01

    Five episodes of micropsia, which were precipitated by oedipal masturbatory fantasies, are described in the analysis of an adult male. Traumatic visual events and testicular retractions during the oedipal and latency years predisposed the ego functions concerned with visual perception to later involvement in conflict. The micropsia itself is seen as defending against castration anxiety by means of a series of unconscious fantasies of denial. These fantasies cause a regression to an earlier mode of visual perception (and to micropsia) characteristic of latency. The defensive modifications of the functions of the ego itself seen in micropsia are closely allied to those seen in the dèjá vu experience and in depersonalization.

  1. Conserved protein domains in a myosin heavy chain gene from Dictyostelium discoideum.

    PubMed Central

    Warrick, H M; De Lozanne, A; Leinwand, L A; Spudich, J A

    1986-01-01

    The 2116-amino acid myosin heavy chain sequence from Dictyostelium discoideum was determined from DNA sequence analysis of the cloned gene. The gene product can be divided into two distinct regions, a globular head region and a long alpha-helical, rod-like tail. In comparisons with nematode and mammalian muscle myosins, specific areas of the head region are highly conserved. These areas presumably reflect conserved functional and structural domains. Certain features that are present in the head region of nematode and mammalian muscle myosins, and that have been assumed to be important for myosin function, are missing in the Dictyostelium myosin sequence. The protein sequence of the Dictyostelium tail region is very poorly conserved with respect to the other myosins but displays the periodicities similar to those of muscle myosins. These periodicities are believed to play a role in filament formation. The 196-residue repeating unit that determines the 14.3-nm repeat seen in muscle thick filaments, the 28-residue charge repeating unit, and the 1,4 hydrophobic repeat previously described for the nematode myosin are all present in the Dictyostelium myosin rod sequence, suggesting that the filament structures of muscle and Dictyostelium myosins must be similar. PMID:3540939

  2. The transcription factor Spn1 regulates gene expression via a highly conserved novel structural motif

    PubMed Central

    Pujari, Venugopal; Radebaugh, Catherine A.; Chodaparambil, Jayanth V.; Muthurajan, Uma M.; Almeida, Adam R.; Fischbeck, Julie A.; Luger, Karolin; Stargell, Laurie A.

    2010-01-01

    Spn1 plays essential roles in the regulation of gene expression by RNA Polymerase II (RNAPII), and it is highly conserved in organisms ranging from yeast to humans. Spn1 physically and/or genetically interacts with RNAPII, TBP, TFIIS and a number of chromatin remodeling factors (Swi/Snf and Spt6). The central domain of Spn1 (residues 141-305 out of 410) is necessary and sufficient for performing the essential functions of SPN1 in yeast cells. Here we report the high-resolution (1.85Å) crystal structure of the conserved central domain of Saccharomyces cerevisiae Spn1. The central domain is comprised of eight alpha-helices in a right handed super helical arrangement, and exhibits structural similarity to domain I of TFIIS. A unique structural feature of Spn1 is a highly conserved loop, which defines one side of a pronounced cavity. The loop and the other residues forming the cavity are highly conserved at the amino acid level among all Spn1 family members, suggesting that this is a signature motif for Spn1 orthologs. The locations and the molecular characterization of temperature-sensitive mutations in Spn1 indicate that the cavity is a key attribute of Spn1 that is critical for its regulatory functions during RNAPII-mediated transcriptional activity. PMID:20875428

  3. The transcription factor Spn1 regulates gene expression via a highly conserved novel structural motif.

    PubMed

    Pujari, Venugopal; Radebaugh, Catherine A; Chodaparambil, Jayanth V; Muthurajan, Uma M; Almeida, Adam R; Fischbeck, Julie A; Luger, Karolin; Stargell, Laurie A

    2010-11-19

    Spn1/Iws1 plays essential roles in the regulation of gene expression by RNA polymerase II (RNAPII), and it is highly conserved in organisms ranging from yeast to humans. Spn1 physically and/or genetically interacts with RNAPII, TBP (TATA-binding protein), TFIIS (transcription factor IIS), and a number of chromatin remodeling factors (Swi/Snf and Spt6). The central domain of Spn1 (residues 141-305 out of 410) is necessary and sufficient for performing the essential functions of SPN1 in yeast cells. Here, we report the high-resolution (1.85 Å) crystal structure of the conserved central domain of Saccharomyces cerevisiae Spn1. The central domain is composed of eight α-helices in a right-handed superhelical arrangement and exhibits structural similarity to domain I of TFIIS. A unique structural feature of Spn1 is a highly conserved loop, which defines one side of a pronounced cavity. The loop and the other residues forming the cavity are highly conserved at the amino acid level among all Spn1 family members, suggesting that this is a signature motif for Spn1 orthologs. The locations and the molecular characterization of temperature-sensitive mutations in Spn1 indicate that the cavity is a key attribute of Spn1 that is critical for its regulatory functions during RNAPII-mediated transcriptional activity.

  4. Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians

    PubMed Central

    Stolfi, Alberto; Lowe, Elijah K; Racioppi, Claudia; Ristoratore, Filomena; Brown, C Titus; Swalla, Billie J; Christiaen, Lionel

    2014-01-01

    Ascidians present a striking dichotomy between conserved phenotypes and divergent genomes: embryonic cell lineages and gene expression patterns are conserved between distantly related species. Much research has focused on Ciona or Halocynthia spp. but development in other ascidians remains poorly characterized. In this study, we surveyed the multipotent myogenic B7.5 lineage in Molgula spp. Comparisons to the homologous lineage in Ciona revealed identical cell division and fate specification events that result in segregation of larval, cardiac, and pharyngeal muscle progenitors. Moreover, the expression patterns of key regulators are conserved, but cross-species transgenic assays uncovered incompatibility, or ‘unintelligibility’, of orthologous cis-regulatory sequences between Molgula and Ciona. These sequences drive identical expression patterns that are not recapitulated in cross-species assays. We show that this unintelligibility is likely due to changes in both cis- and trans-acting elements, hinting at widespread and frequent turnover of regulatory mechanisms underlying otherwise conserved aspects of ascidian embryogenesis. DOI: http://dx.doi.org/10.7554/eLife.03728.001 PMID:25209999

  5. Composition and Expression of Conserved MicroRNA Genes in Diploid Cotton (Gossypium) Species

    PubMed Central

    Gong, Lei; Kakrana, Atul; Arikit, Siwaret; Meyers, Blake C.; Wendel, Jonathan F.

    2013-01-01

    MicroRNAs are ubiquitous in plant genomes but vary greatly in their abundance within and conservation among plant lineages. To gain insight into the evolutionary birth/death dynamics of microRNA families, we sequenced small RNA and 5′-end PARE libraries generated from two closely related species of Gossypium. Here, we demonstrate that 33 microRNA families, with similar copy numbers and average evolutionary rates, are conserved in the two congeneric cottons. Analysis of the presence/absence of these microRNA families in other land plants sheds light on their depth of phylogenetic origin and lineage-specific loss/gain. Conserved microRNA families in Gossypium exhibit a striking interspecific asymmetry in expression, potentially connected to relative proximity to neighboring transposable elements. A complex correlated expression pattern of microRNA target genes with their controlling microRNAs indicates that possible functional divergence of conserved microRNA families can also exist even within a single plant genus. PMID:24281048

  6. General Information about Testicular Cancer

    MedlinePlus

    ... 3 tumor markers are used in staging testicular cancer : Alpha-fetoprotein (AFP) Beta-human chorionic gonadotropin (β-hCG). Lactate dehydrogenase (LDH). Tumor marker levels are measured again, ...

  7. Testicular Cancer Treatments: After Treatment

    MedlinePlus

    ... to alphafetoprotein (AFP), beta-hCG (b-hCG), and lactate dehydrogenase (LDH). AFP and b-hCG are proteins ... Our recommendations are divided by type of testicular cancer, stage, and treatment given. Clinical Stage I Nonseminoma - ...

  8. How to Perform a Testicular Self-Examination

    MedlinePlus

    ... Can Get Weight Loss Surgery? Choosing the Right Sport for You Shyness How to Do a Testicular ... autoexamen testicular Testicular self-exams (TSE) can help you check for things like cancer. Although testicular cancer is rare in teenage guys, ...

  9. What's New in Testicular Cancer Research and Treatment?

    MedlinePlus

    ... and Treatment? Testicular Cancer About Testicular Cancer What’s New in Testicular Cancer Research and Treatment? Important research ... findings may help individualize treatment and help find new drugs to treat testicular cancer that can target ...

  10. Origin of INSL3-mediated testicular descent in therian mammals.

    PubMed

    Park, Jae-Il; Semyonov, Jenia; Chang, Chia Lin; Yi, Wei; Warren, Wesley; Hsu, Sheau Yu Teddy

    2008-06-01

    Testicular descent is a unique physiological adaptation found in therian mammals allowing optimal spermatogenesis below core body temperature. Recent studies show that INSL3, produced by Leydig cells, and its receptor LGR8 (RXFP2) are essential for mediating the transabdominal phase of testicular descent during early development. However, the origin and genetic basis for this physiological adaptation is not clear. Using syntenic mapping and the functional characterization of contemporary and resurrected relaxin family hormones, we show that derivation of INSL3-mediated testicular descent involved the duplication of an ancestral RLN3-like gene that encodes an indiscriminate ligand for LGR7 (RXFP1) and LGR8. This event was followed by acquisition of the LGR7-selective characteristics by a daughter gene (RLN3) prior to the evolution of the common ancestor of monotremes, marsupials, and placentals. A subsequent mutation of the other daughter gene (INSL3) occurred before the emergence of therian mammals, which then led to the derivation of the reciprocal LGR8-specific characteristics of INSL3. The stepwise evolution of these independent signaling pathways through gene duplication and subsequent divergence is consistent with Darwinian theory of selection and adaptation, and the temporal proximity suggests an association between these genetic events and the concurrent evolution of testicular descent in ancestral therian mammals.

  11. Cancer in first-degree relatives and risk of testicular cancer in Denmark.

    PubMed

    Nordsborg, Rikke Baastrup; Meliker, Jaymie R; Wohlfahrt, Jan; Melbye, Mads; Raaschou-Nielsen, Ole

    2011-11-15

    Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population-based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3,297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. A total of 6,594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyze whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio for testicular cancer was 4.63 (95% CI: 2.41-8.87) when a father, 8.30 (95% CI: 3.81-18.10) when a brother and 5.23 (95% CI: 1.35-20.26) when a son had testicular cancer compared to no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial non-Hodgkin lymphoma and esophageal cancer were associated with testicular cancer; however, these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine.

  12. Human growth is associated with distinct patterns of gene expression in evolutionarily conserved networks

    PubMed Central

    2013-01-01

    Background A co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth. Results We conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth – infancy, childhood, puberty and final height. Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor – Hyper-geometric test, q < 0.05). The greatest degree of network ‘connectivity’ and hence functional significance was present in infancy (Wilcoxon test, p < 0.05), which then decreased through to adulthood. These observations were confirmed in a separate validation data set from lymphoid tissue. Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation. Conclusions Similar evolutionarily conserved pathways have been associated with gene expression and child growth in multiple tissues. These expression profiles associate with the developmental phases

  13. Structural genomics of highly conserved microbial genes of unknown function in search of new antibacterial targets.

    PubMed

    Abergel, Chantal; Coutard, Bruno; Byrne, Deborah; Chenivesse, Sabine; Claude, Jean-Baptiste; Deregnaucourt, Céline; Fricaux, Thierry; Gianesini-Boutreux, Celine; Jeudy, Sandra; Lebrun, Régine; Maza, Caroline; Notredame, Cédric; Poirot, Olivier; Suhre, Karsten; Varagnol, Majorie; Claverie, Jean-Michel

    2003-01-01

    With more than 100 antibacterial drugs at our disposal in the 1980's, the problem of bacterial infection was considered solved. Today, however, most hospital infections are insensitive to several classes of antibacterial drugs, and deadly strains of Staphylococcus aureus resistant to vancomycin--the last resort antibiotic--have recently begin to appear. Other life-threatening microbes, such as Enterococcus faecalis and Mycobacterium tuberculosis are already able to resist every available antibiotic. There is thus an urgent, and continuous need for new, preferably large-spectrum, antibacterial molecules, ideally targeting new biochemical pathways. Here we report on the progress of our structural genomics program aiming at the discovery of new antibacterial gene targets among evolutionary conserved genes of uncharacterized function. A series of bioinformatic and comparative genomics analyses were used to identify a set of 221 candidate genes common to Gram-positive and Gram-negative bacteria. These genes were split between two laboratories. They are now submitted to a systematic 3-D structure determination protocol including cloning, protein expression and purification, crystallization, X-ray diffraction, structure interpretation, and function prediction. We describe here our strategies for the 111 genes processed in our laboratory. Bioinformatics is used at most stages of the production process and out of 111 genes processed--and 17 months into the project--108 have been successfully cloned, 103 have exhibited detectable expression, 84 have led to the production of soluble protein, 46 have been purified, 12 have led to usable crystals, and 7 structures have been determined.

  14. Conservation of DNA photolyase genes in group II nucleopolyhedroviruses infecting plusiine insects.

    PubMed

    Xu, Fang; Vlak, Just M; van Oers, Monique M

    2008-09-01

    DNA photolyase genes (phr) encode photoreactive enzymes, which are involved in the repair of UV-damaged DNA. Cyclobutane pyrimidine dimer (CPD) specific photolyase genes are present in nucleopolyhedroviruses isolated from Chrysodeixis chalcites (ChchNPV) and Trichoplusia ni (TnSNPV), insects belonging to the Plusiinae (Noctuidae). To better understand the occurrence and evolution of these genes in baculoviruses, we investigated their possible conservation in other group II NPVs, which infect plusiine insects. A PCR based strategy using degenerate phr-specific primers was designed to detect and analyze possible photolyase genes. Six additional Plusiinae-infecting NPVs were analyzed and all, except Thysanoplusia oricalcea NPV A28-1, which is a group I NPV, contained one or more phr-like sequences. Phylogenetic analysis revealed that all photolyase genes of the tested Plusiinae-infecting baculoviruses group in a single clade, separated into three subgroups. The phylogeny of the polyhedrin sequences of these viruses confirmed that the analyzed viruses also formed a single clade in group II NPVs. We hypothesize that all plusiine group II NPVs contain one or more photolyase genes and that these have a common ancestor.

  15. Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

    PubMed Central

    Watson, D K; McWilliams, M J; Lapis, P; Lautenberger, J A; Schweinfest, C W; Papas, T S

    1988-01-01

    Cellular ets sequences homologous to v-ets of the avian leukemia virus E26 are highly conserved. In mammals the ets sequences are dispersed on two separate chromosomal loci, called ets-1 and ets-2. To determine the structure of these two genes and identify the open reading frames that code for the putative proteins, we have sequenced human ets-1 cDNAs and ets-2 cDNA clones obtained from both human and mouse. The human ETS1 gene is capable of encoding a protein of 441 amino acids. This protein is greater than 95% identical to the chicken c-ets-1 gene product. Thus, the human ETS1 gene is homologous to the chicken c-ets-1 gene, the protooncogene that the E26 virus transduced. Human and mouse ets-2 cDNA clones are closely related and contain open reading frames capable of encoding proteins of 469 and 468 residues, respectively. Direct comparison of these data with previously published findings indicates that ets is a family of genes whose members share distinct domains. PMID:2847145

  16. HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human.

    PubMed Central

    Bedford, F K; Ashworth, A; Enver, T; Wiedemann, L M

    1993-01-01

    We describe the cloning of a novel homeodomain-containing gene, which is highly conserved between mouse and human. The human cDNA was initially isolated from human haematopoietic tissue and denoted HEX (haematopoietically expressed homeobox). Sequence analysis of the coding sequences from mouse and the partial cDNA from human shows that the homeodomain is most closely related to those of the HIx and HOX11 proteins. The HEX gene is present as a single copy in the human genome. Analysis of murine genomic DNA shows, in addition to an intron-containing gene homologous to HEX, the presence of a processed copy of the gene which has arisen within the last few million years. Analysis of human and murine haematopoietic cells and cell lines, revealed expression of the HEX gene in multipotential progenitors, as well as cells of the B-lymphocyte and myeloid lineages. However HEX was not expressed in T-lymphocytes or erythroid cells. This pattern of HEX gene expression suggests that it may play a role in haematopoietic differentiation. Images PMID:8096636

  17. Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences

    PubMed Central

    Meyer, Kyle A.; Marques-Bonet, Tomas

    2017-01-01

    Previous studies have found that genes which are differentially expressed within the developing human brain disproportionately neighbor conserved noncoding sequences (CNSs) that have an elevated substitution rate in humans and in other species. One explanation for this general association of differential expression with accelerated CNSs is that genes with pre-existing patterns of differential expression have been preferentially targeted by species-specific regulatory changes. Here we provide support for an alternative explanation: genes that neighbor a greater number of CNSs have a higher probability of differential expression and a higher probability of neighboring a CNS with lineage-specific acceleration. Thus, neighboring an accelerated element from any species signals that a gene likely neighbors many CNSs. We extend the analyses beyond the prenatal time points considered in previous studies to demonstrate that this association persists across developmental and adult periods. Examining differential expression between non-neural tissues suggests that the relationship between the number of CNSs a gene neighbors and its differential expression status may be particularly strong for expression differences among brain regions. In addition, by considering this relationship, we highlight a recently defined set of putative human-specific gain-of-function sequences that, even after adjusting for the number of CNSs neighbored by genes, shows a positive relationship with upregulation in the brain compared with other tissues examined. PMID:28204568

  18. Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

    PubMed Central

    2011-01-01

    Background Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. Results By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. Conclusions Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell. PMID:21226929

  19. Neonatal Testicular Torsion; a Review Article

    PubMed Central

    Riaz-Ul-haq, Muhammad; Mahdi, Diaa Eldin Abdelhamid; Elhassan, Elbagir Uthman

    2012-01-01

    Neonatal testicular torsion, also known as perinatal testicular torsion is a subject of debate among surgeons. Neonatal testicular torsion either intrauterine or postnatal results into extravaginal torsion which is a different entity than intravaginal type but has the same devastating consequences if not diagnosed and managed well in time. Testicular torsion results into acute ischemia with its resultant sequelae such as abnormality of testicular function and fertility. Urgent surgical exploration and fixation of the other testis are the key points in the management. General anesthesia is not a contraindication for exploration as thought before. Diagnosis and controversies on management of testicular torsion are discussed in this review. PMID:23400637

  20. Conserved Overlapping Gene Arrangement, Restricted Expression, and Biochemical Activities of DNA Polymerase ν (POLN)*

    PubMed Central

    Takata, Kei-ichi; Tomida, Junya; Reh, Shelley; Swanhart, Lisa M.; Takata, Minoru; Hukriede, Neil A.; Wood, Richard D.

    2015-01-01

    DNA polymerase ν (POLN) is one of 16 DNA polymerases encoded in vertebrate genomes. It is important to determine its gene expression patterns, biological roles, and biochemical activities. By quantitative analysis of mRNA expression, we found that POLN from the zebrafish Danio rerio is expressed predominantly in testis. POLN is not detectably expressed in zebrafish embryos or in mouse embryonic stem cells. Consistent with this, injection of POLN-specific morpholino antisense oligonucleotides did not interfere with zebrafish embryonic development. Analysis of transcripts revealed that vertebrate POLN has an unusual gene expression arrangement, sharing a first exon with HAUS3, the gene encoding augmin-like complex subunit 3. HAUS3 is broadly expressed in embryonic and adult tissues, in contrast to POLN. Differential expression of POLN and HAUS3 appears to arise by alternate splicing of transcripts in mammalian cells and zebrafish. When POLN was ectopically overexpressed in human cells, it specifically coimmunoprecipitated with the homologous recombination factors BRCA1 and FANCJ, but not with previously suggested interaction partners (HELQ and members of the Fanconi anemia core complex). Purified zebrafish POLN protein is capable of thymine glycol bypass and strand displacement, with activity dependent on a basic amino acid residue known to stabilize the primer-template. These properties are conserved with the human enzyme. Although the physiological function of pol ν remains to be clarified, this study uncovers distinctive aspects of its expression control and evolutionarily conserved properties of this DNA polymerase. PMID:26269593

  1. Conserved and diversified gene families of monovalent cation/h(+) antiporters from algae to flowering plants.

    PubMed

    Chanroj, Salil; Wang, Guoying; Venema, Kees; Zhang, Muren Warren; Delwiche, Charles F; Sze, Heven

    2012-01-01

    All organisms have evolved strategies to regulate ion and pH homeostasis in response to developmental and environmental cues. One strategy is mediated by monovalent cation-proton antiporters (CPA) that are classified in two superfamilies. Many CPA1 genes from bacteria, fungi, metazoa, and plants have been functionally characterized; though roles of plant CPA2 genes encoding K(+)-efflux antiporter (KEA) and cation/H(+) exchanger (CHX) families are largely unknown. Phylogenetic analysis showed that three clades of the CPA1 Na(+)-H(+) exchanger (NHX) family have been conserved from single-celled algae to Arabidopsis. These are (i) plasma membrane-bound SOS1/AtNHX7 that share ancestry with prokaryote NhaP, (ii) endosomal AtNHX5/6 that is part of the eukaryote Intracellular-NHE clade, and (iii) a vacuolar NHX clade (AtNHX1-4) specific to plants. Early diversification of KEA genes possibly from an ancestral cyanobacterium gene is suggested by three types seen in all plants. Intriguingly, CHX genes diversified from three to four members in one subclade of early land plants to 28 genes in eight subclades of Arabidopsis. Homologs from Spirogyra or Physcomitrella share high similarity with AtCHX20, suggesting that guard cell-specific AtCHX20 and its closest relatives are founders of the family, and pollen-expressed CHX genes appeared later in monocots and early eudicots. AtCHX proteins mediate K(+) transport and pH homeostasis, and have been localized to intracellular and plasma membrane. Thus KEA genes are conserved from green algae to angiosperms, and their presence in red algae and secondary endosymbionts suggest a role in plastids. In contrast, AtNHX1-4 subtype evolved in plant cells to handle ion homeostasis of vacuoles. The great diversity of CHX genes in land plants compared to metazoa, fungi, or algae would imply a significant role of ion and pH homeostasis at dynamic endomembranes in the vegetative and reproductive success of flowering plants.

  2. Conserved and Diversified Gene Families of Monovalent Cation/H+ Antiporters from Algae to Flowering Plants

    PubMed Central

    Chanroj, Salil; Wang, Guoying; Venema, Kees; Zhang, Muren Warren; Delwiche, Charles F.; Sze, Heven

    2012-01-01

    All organisms have evolved strategies to regulate ion and pH homeostasis in response to developmental and environmental cues. One strategy is mediated by monovalent cation–proton antiporters (CPA) that are classified in two superfamilies. Many CPA1 genes from bacteria, fungi, metazoa, and plants have been functionally characterized; though roles of plant CPA2 genes encoding K+-efflux antiporter (KEA) and cation/H+ exchanger (CHX) families are largely unknown. Phylogenetic analysis showed that three clades of the CPA1 Na+–H+ exchanger (NHX) family have been conserved from single-celled algae to Arabidopsis. These are (i) plasma membrane-bound SOS1/AtNHX7 that share ancestry with prokaryote NhaP, (ii) endosomal AtNHX5/6 that is part of the eukaryote Intracellular-NHE clade, and (iii) a vacuolar NHX clade (AtNHX1–4) specific to plants. Early diversification of KEA genes possibly from an ancestral cyanobacterium gene is suggested by three types seen in all plants. Intriguingly, CHX genes diversified from three to four members in one subclade of early land plants to 28 genes in eight subclades of Arabidopsis. Homologs from Spirogyra or Physcomitrella share high similarity with AtCHX20, suggesting that guard cell-specific AtCHX20 and its closest relatives are founders of the family, and pollen-expressed CHX genes appeared later in monocots and early eudicots. AtCHX proteins mediate K+ transport and pH homeostasis, and have been localized to intracellular and plasma membrane. Thus KEA genes are conserved from green algae to angiosperms, and their presence in red algae and secondary endosymbionts suggest a role in plastids. In contrast, AtNHX1–4 subtype evolved in plant cells to handle ion homeostasis of vacuoles. The great diversity of CHX genes in land plants compared to metazoa, fungi, or algae would imply a significant role of ion and pH homeostasis at dynamic endomembranes in the vegetative and reproductive success of flowering plants. PMID:22639643

  3. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

    PubMed Central

    Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Graves, Tina; Fulton, Robert S.; Dugan, Shannon; Ding, Yan; Buhay, Christian J.; Kremitzki, Colin; Wang, Qiaoyan; Shen, Hua; Holder, Michael; Villasana, Donna; Nazareth, Lynne V.; Cree, Andrew; Courtney, Laura; Veizer, Joelle; Kotkiewicz, Holland; Cho, Ting-Jan; Koutseva, Natalia; Rozen, Steve; Muzny, Donna M.; Warren, Wesley C.; Gibbs, Richard A.; Wilson, Richard K.; Page, David C.

    2012-01-01

    The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200–300 million years1–3. Due to genetic decay, the human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes’ genes4,5. This evolutionary decay was driven by a series of five “stratification” events. Each event suppressed X-Y crossing over within a chromosome segment or “stratum”, incorporated that segment into the MSY, and subjected its genes to the erosive forces that attend the absence of crossing over2,6. The last of these events occurred 30 million years ago (mya), or 5 million years before the human and Old World monkey (OWM) lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome7–10, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the OWM lineage. To explore this question, we sequenced the MSY of the rhesus macaque, an OWM, and compared it to the human MSY. We discovered that, during the last 25 million years, MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. Within the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 mya. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite major structural differences from the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection. PMID:22367542

  4. Testicular thecoma in an 11-year-old boy with nevoid basal-cell carcinoma syndrome (Gorlin syndrome).

    PubMed

    Ueda, Masakatsu; Kanematsu, Akihiro; Nishiyama, Hiroyuki; Yoshimura, Koji; Watanabe, Kenichiro; Yorifuji, Tohru; Mikami, Yoshiki; Kamoto, Toshiyuki; Ogawa, Osamu

    2010-03-01

    We report a case of testicular thecoma in an 11-year-old Japanese boy with nevoid basal-cell carcinoma syndrome (Gorlin syndrome). He presented with left testicular swelling and underwent a radical orchiectomy on suspicion of a malignant paratesticular tumor. The tumor arose from the testis exophytically and was diagnosed as a thecoma histopathologically. Ovarian thecoma-fibroma group tumors are closely associated with Gorlin syndrome or with abnormalities in PTCH, a candidate gene for the syndrome. The occurrence of an extremely rare testicular thecoma in this case (the second in the literature) suggests that such an etiological association may also exist in the pathogenesis of testicular tumors.

  5. Chromosome banding and gene localizations support extensive conservation of chromosome structure between cattle and sheep.

    PubMed

    Hediger, R; Ansari, H A; Stranzinger, G F

    1991-01-01

    By using three gene probes, one derived from the porcine major histocompatibility complex (MHC) and two from bovine cytokeratin genes, type I (KRTA) and type II (KRTB), the hypothesis of conservation of genome structure in two members of the family Bovidae was examined. Gene mapping data revealed the MHC to be in chromosome region 23q15----q23 in cattle (BOLA) and 20q15----q23 in sheep (OLA). KRTA was localized to chromosome region 19q25----q29 in cattle and 11q25----q29 in sheep and KRTB to 5q14----q22 in cattle and 3q14----q22 in sheep. The banding patterns of the chromosome arms to which the loci were assigned were identical in both species. Moreover, the resemblances of GTG- or QFQ-banding patterns between the cattle and sheep karyotypes illustrated further chromosome homologies. These studies, based on gene mapping comparisons and comparative cytogenetics, document that within bovid chromosomes, homology of banding patterns corresponds to a homologous genetic structure. Hence, we propose that gene assignments on identified chromosomal segments in one species of the Bovidae can be extrapolated, in general, to other bovid species based on the banding homologies presented here.

  6. Adoption of conserved developmental genes in development and origin of the medusa body plan.

    PubMed

    Kraus, Johanna E M; Fredman, David; Wang, Wei; Khalturin, Konstantin; Technau, Ulrich

    2015-01-01

    The metagenesis of sessile polyps into pelagic medusae in cnidarians represents one of the most ancient complex life cycles in animals. Interestingly, scyphozoans and hydrozoans generate medusae by apparently fundamentally different processes. It is therefore unclear whether medusa formation has evolved independently in different medusozoans. To this end, a thorough understanding of the correspondence of polyp and medusa is required. We monitored the expression patterns of conserved developmental genes in developing medusae of Clytia hemisphaerica (Hydrozoa) and Aurelia aurita (Scyphozoa) and found that developing medusae and polyps share similarities in their morphology and developmental gene expression. Unexpectedly, however, polyp tentacle marker genes were consistently expressed in the developing medusa bell, suggesting that the bell of medusae corresponds to modified and fused polyp tentacle anlagen. Our data represent the first comparative gene expression analysis of developing medusae in two representatives of Scyphozoa and Hydrozoa. The results challenge prevailing views about polyp medusa body plan homology. We propose that the evolution of a new life stage may be facilitated by the adoption of existing developmental genes.

  7. Testicular cancer and antecedent diseases.

    PubMed

    Swerdlow, A J; Huttly, S R; Smith, P G

    1987-01-01

    A case-control study of the aetiology of testicular cancer was conducted using information obtained by interview and from case-notes of 259 cases with testicular cancer and two sets of control patients -238 men with diagnoses other than testicular cancer attending the same radiotherapy centres as those attended by the cases, and 251 hospital in-patients not attending radiotherapy departments. Logistic regression analyses were performed, after stratifying by age and region of residence, to estimate the relative risks (RRs) associated with various aspects of prior medical history. The risk of testicular cancer was found to be raised for men with a history of cryptorchidism (RR based on comparison with all controls = 6.3; P less than 0.001), inguinal hernia (RR = 1.6; P = 0.14), mumps orchitis (RR = 12.7; P = 0.006), atopy (RR = 1.8; P = 0.03), and meningitis (RR = 3.0; P = 0.21). Inguinal herniorrhaphy before the age of 15 years was particularly a risk factor for seminoma, whereas the relative risks were similar for seminoma and teratoma for the other factors. The results add to the growing evidence that congenital abnormalities involving the process of testicular descent and closure of the processus vaginalis are risk factors for testicular cancer, and that some types of testicular damage later in life may also be important. The findings of associations with previous atopy and certain infections suggest a possible second aetiological mechanism - that immunological abnormalities may be associated with an increased risk of testis cancer.

  8. Chromosomal mapping and genomic organization of an evolutionarily conserved zinc finger gene ZNF277.

    PubMed

    Liang, H; Guo, W; Nagarajan, L

    2000-06-01

    A novel C2H2 zinc finger gene, ZNF277, has been localized to human chromosome 7q31.1. The gene is encoded by 12 exons in a genomic fragment of >100 kb between the microsatellite markers D7S523 and D7S471, deleted in a number of malignancies. The predicted open reading frame (ORF) of 438 amino acids shows an overall homology of 50% to the putative ORF F46B6.7 of Caenorhabditis elegans. The presence of a 30-amino-acid coiled-coil domain in both the C. elegans ORF F46B6.7 and ZNF277 is suggestive of functional similarities. ESTs for the murine orthologue ZFP277 are found in early embryonic stem cells, 16-cell stage embryo, and blastocysts. The evolutionary conservation and the expression profile suggest ZNF277 to be a critical regulator of development and differentiation. Copyright 2000 Academic Press.

  9. Phylogenetic conservation and physical mapping of members of the H6 homeobox gene family.

    PubMed

    Stadler, H S; Murray, J C; Leysens, N J; Goodfellow, P J; Solursh, M

    1995-06-01

    Homeobox genes represent a class of transcription factors that play key roles in the regulation of embryogenesis and development. Here we report the identification of a homeobox-containing gene family that is highly conserved at both the nucleotide and amino acid levels in a diverse number of species. These species encompass both vertebrate and invertebrate phylogenies, ranging from Homo sapiens to Drosophila melanogaster. In humans, at least two homeobox sequences from this family were identified representing a previously reported member of this family as well as a novel homeobox sequence that we physically mapped to the 10q25.2-q26.3 region of human Chromosome (Chr) 10. Multiple members of this family were also detected in three additional vertebrate species including Equus caballus (horse), Gallus gallus (Chicken), and Mus musculus (mouse), whereas only single members were detected in Tripneustes gratilla (sea urchin), Petromyzon marinus (lamprey), Salmo salar (salmon), Ovis aries (sheep), and D. melanogaster (fruit fly).

  10. The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences.

    PubMed Central

    Fierro, F; Barredo, J L; Díez, B; Gutierrez, S; Fernández, F J; Martín, J F

    1995-01-01

    The penicillin biosynthetic genes (pcbAB, pcbC, penDE) of Penicillium chrysogenum AS-P-78 were located in a 106.5-kb DNA region that is amplified in tandem repeats (five or six copies) linked by conserved TTTACA sequences. The wild-type strains P. chrysogenum NRRL 1951 and Penicillium notatum ATCC 9478 (Fleming's isolate) contain a single copy of the 106.5-kb region. This region was bordered by the same TTTACA hexanucleotide found between tandem repeats in strain AS-P-78. A penicillin overproducer strain, P. chrysogenum E1, contains a large number of copies in tandem of a 57.9-kb DNA fragment, linked by the same hexanucleotide or its reverse complementary TGTAAA sequence. The deletion mutant P. chrysogenum npe10 showed a deletion of 57.9 kb that corresponds exactly to the DNA fragment that is amplified in E1. The conserved hexanucleotide sequence was reconstituted at the deletion site. The amplification has occurred within a single chromosome (chromosome I). The tandem reiteration and deletion appear to arise by mutation-induced site-specific recombination at the conserved hexanucleotide sequences. Images Fig. 3 PMID:7597101

  11. The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences.

    PubMed

    Fierro, F; Barredo, J L; Díez, B; Gutierrez, S; Fernández, F J; Martín, J F

    1995-06-20

    The penicillin biosynthetic genes (pcbAB, pcbC, penDE) of Penicillium chrysogenum AS-P-78 were located in a 106.5-kb DNA region that is amplified in tandem repeats (five or six copies) linked by conserved TTTACA sequences. The wild-type strains P. chrysogenum NRRL 1951 and Penicillium notatum ATCC 9478 (Fleming's isolate) contain a single copy of the 106.5-kb region. This region was bordered by the same TTTACA hexanucleotide found between tandem repeats in strain AS-P-78. A penicillin overproducer strain, P. chrysogenum E1, contains a large number of copies in tandem of a 57.9-kb DNA fragment, linked by the same hexanucleotide or its reverse complementary TGTAAA sequence. The deletion mutant P. chrysogenum npe10 showed a deletion of 57.9 kb that corresponds exactly to the DNA fragment that is amplified in E1. The conserved hexanucleotide sequence was reconstituted at the deletion site. The amplification has occurred within a single chromosome (chromosome I). The tandem reiteration and deletion appear to arise by mutation-induced site-specific recombination at the conserved hexanucleotide sequences.

  12. Conservation and diversity of gene families explored using the CODEHOP strategy in higher plants

    PubMed Central

    Morant, Marc; Hehn, Alain; Werck-Reichhart, Danièle

    2002-01-01

    Background Availability of genomewide information on an increasing but still limited number of plants offers the possibility of identifying orthologues, or related genes, in species with major economical impact and complex genomes. In this paper we exploit the recently described CODEHOP primer design and PCR strategy for targeted isolation of homologues in large gene families. Results The method was tested with two different objectives. The first was to analyze the evolution of the CYP98 family of cytochrome P450 genes involved in 3-hydroxylation of phenolic compounds and lignification in a broad range of plant species. The second was to isolate an orthologue of the sorghum glucosyl transferase UGT85B1 and to determine the complexity of the UGT85 family in wheat. P450s of the CYP98 family or closely related sequences were found in all vascular plants. No related sequence was found in moss. Neither extensive duplication of the CYP98 genes nor an orthologue of UGT85B1 were found in wheat. The UGT85A subfamily was however found to be highly variable in wheat. Conclusions Our data are in agreement with the implication of CYP98s in lignification and the evolution of 3-hydroxylation of lignin precursors with vascular plants. High conservation of the CYP98 family strongly argues in favour of an essential function in plant development. Conversely, high duplication and diversification of the UGT85A gene family in wheat suggests its involvement in adaptative response and provides a valuable pool of genes for biotechnological applications. This work demonstrates the high potential of the CODEHOP strategy for the exploration of large gene families in plants. PMID:12153706

  13. Conservation and divergence of autonomous pathway genes in the flowering regulatory network of Beta vulgaris.

    PubMed

    Abou-Elwafa, Salah F; Büttner, Bianca; Chia, Tansy; Schulze-Buxloh, Gretel; Hohmann, Uwe; Mutasa-Göttgens, Effie; Jung, Christian; Müller, Andreas E

    2011-06-01

    The transition from vegetative growth to reproductive development is a complex process that requires an integrated response to multiple environmental cues and endogenous signals. In Arabidopsis thaliana, which has a facultative requirement for vernalization and long days, the genes of the autonomous pathway function as floral promoters by repressing the central repressor and vernalization-regulatory gene FLC. Environmental regulation by seasonal changes in daylength is under control of the photoperiod pathway and its key gene CO. The root and leaf crop species Beta vulgaris in the caryophyllid clade of core eudicots, which is only very distantly related to Arabidopsis, is an obligate long-day plant and includes forms with or without vernalization requirement. FLC and CO homologues with related functions in beet have been identified, but the presence of autonomous pathway genes which function in parallel to the vernalization and photoperiod pathways has not yet been reported. Here, this begins to be addressed by the identification and genetic mapping of full-length homologues of the RNA-regulatory gene FLK and the chromatin-regulatory genes FVE, LD, and LDL1. When overexpressed in A. thaliana, BvFLK accelerates bolting in the Col-0 background and fully complements the late-bolting phenotype of an flk mutant through repression of FLC. In contrast, complementation analysis of BvFVE1 and the presence of a putative paralogue in beet suggest evolutionary divergence of FVE homologues. It is further shown that BvFVE1, unlike FVE in Arabidopsis, is under circadian clock control. Together, the data provide first evidence for evolutionary conservation of components of the autonomous pathway in B. vulgaris, while also suggesting divergence or subfunctionalization of one gene. The results are likely to be of broader relevance because B. vulgaris expands the spectrum of evolutionarily diverse species which are subject to differential developmental and/or environmental regulation

  14. Conservation and divergence of autonomous pathway genes in the flowering regulatory network of Beta vulgaris

    PubMed Central

    Abou-Elwafa, Salah F.; Büttner, Bianca; Chia, Tansy; Schulze-Buxloh, Gretel; Hohmann, Uwe; Mutasa-Göttgens, Effie; Jung, Christian; Müller, Andreas E.

    2011-01-01

    The transition from vegetative growth to reproductive development is a complex process that requires an integrated response to multiple environmental cues and endogenous signals. In Arabidopsis thaliana, which has a facultative requirement for vernalization and long days, the genes of the autonomous pathway function as floral promoters by repressing the central repressor and vernalization-regulatory gene FLC. Environmental regulation by seasonal changes in daylength is under control of the photoperiod pathway and its key gene CO. The root and leaf crop species Beta vulgaris in the caryophyllid clade of core eudicots, which is only very distantly related to Arabidopsis, is an obligate long-day plant and includes forms with or without vernalization requirement. FLC and CO homologues with related functions in beet have been identified, but the presence of autonomous pathway genes which function in parallel to the vernalization and photoperiod pathways has not yet been reported. Here, this begins to be addressed by the identification and genetic mapping of full-length homologues of the RNA-regulatory gene FLK and the chromatin-regulatory genes FVE, LD, and LDL1. When overexpressed in A. thaliana, BvFLK accelerates bolting in the Col-0 background and fully complements the late-bolting phenotype of an flk mutant through repression of FLC. In contrast, complementation analysis of BvFVE1 and the presence of a putative paralogue in beet suggest evolutionary divergence of FVE homologues. It is further shown that BvFVE1, unlike FVE in Arabidopsis, is under circadian clock control. Together, the data provide first evidence for evolutionary conservation of components of the autonomous pathway in B. vulgaris, while also suggesting divergence or subfunctionalization of one gene. The results are likely to be of broader relevance because B. vulgaris expands the spectrum of evolutionarily diverse species which are subject to differential developmental and/or environmental regulation

  15. Analysis of Sequence, Map Position, and Gene Expression Reveals Conserved Essential Genes for Iron Uptake in Arabidopsis and Tomato1[w

    PubMed Central

    Bauer, Petra; Thiel, Thomas; Klatte, Marco; Bereczky, Zsolt; Brumbarova, Tzvetina; Hell, Rüdiger; Grosse, Ivo

    2004-01-01

    Arabidopsis (Arabidopsis thaliana) and tomato (Lycopersicon esculentum) show similar physiological responses to iron deficiency, suggesting that homologous genes are involved. Essential gene functions are generally considered to be carried out by orthologs that have remained conserved in sequence and map position in evolutionarily related species. This assumption has not yet been proven for plant genomes that underwent large genome rearrangements. We addressed this question in an attempt to deduce functional gene pairs for iron reduction, iron transport, and iron regulation between Arabidopsis and tomato. Iron uptake processes are essential for plant growth. We investigated iron uptake gene pairs from tomato and Arabidopsis, namely sequence, conserved gene content of the regions containing iron uptake homologs based on conserved orthologous set marker analysis, gene expression patterns, and, in two cases, genetic data. Compared to tomato, the Arabidopsis genome revealed more and larger gene families coding for the iron uptake functions. The number of possible homologous pairs was reduced if functional expression data were taken into account in addition to sequence and map position. We predict novel homologous as well as partially redundant functions of ferric reductase-like and iron-regulated transporter-like genes in Arabidopsis and tomato. Arabidopsis nicotianamine synthase genes encode a partially redundant family. In this study, Arabidopsis gene redundancy generally reflected the presumed genome duplication structure. In some cases, statistical analysis of conserved gene regions between tomato and Arabidopsis suggested a common evolutionary origin. Although involvement of conserved genes in iron uptake was found, these essential genes seem to be of paralogous rather than orthologous origin in tomato and Arabidopsis. PMID:15531708

  16. Comprehensive analysis of imprinted genes in maize reveals allelic variation for imprinting and limited conservation with other species.

    PubMed

    Waters, Amanda J; Bilinski, Paul; Eichten, Steven R; Vaughn, Matthew W; Ross-Ibarra, Jeffrey; Gehring, Mary; Springer, Nathan M

    2013-11-26

    In plants, a subset of genes exhibit imprinting in endosperm tissue such that expression is primarily from the maternal or paternal allele. Imprinting may arise as a consequence of mechanisms for silencing of transposons during reproduction, and in some cases imprinted expression of particular genes may provide a selective advantage such that it is conserved across species. Separate mechanisms for the origin of imprinted expression patterns and maintenance of these patterns may result in substantial variation in the targets of imprinting in different species. Here we present deep sequencing of RNAs isolated from reciprocal crosses of four diverse maize genotypes, providing a comprehensive analysis that allows evaluation of imprinting at more than 95% of endosperm-expressed genes. We find that over 500 genes exhibit statistically significant parent-of-origin effects in maize endosperm tissue, but focused our analyses on a subset of these genes that had >90% expression from the maternal allele (69 genes) or from the paternal allele (108 genes) in at least one reciprocal cross. Over 10% of imprinted genes show evidence of allelic variation for imprinting. A comparison of imprinting in maize and rice reveals that 13% of genes with syntenic orthologs in both species exhibit conserved imprinting. Genes that exhibit conserved imprinting between maize and rice have elevated nonsynonymous to synonymous substitution ratios compared with other imprinted genes, suggesting a history of more rapid evolution. Together, these data suggest that imprinting only has functional relevance at a subset of loci that currently exhibit imprinting in maize.

  17. How to Do a Testicular Self Examination

    MedlinePlus

    ... of good testicular self exam sites on the internet A good article on several testicular problems, including illustrations Information on a variety of health issues affecting Men Click on this to go back ...

  18. Can Testicular Cancer Be Found Early?

    MedlinePlus

    ... testicular cancer diagnosed? ). This is an easy and painless way of finding a tumor. If you choose ... editors, and translators with extensive experience in medical writing. See all references for Testicular Cancer Last Medical ...

  19. Testicular Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Testicular Cancer URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Testicular Cancer - Multiple Languages To use the sharing features on ...

  20. On the power and limits of evolutionary conservation--unraveling bacterial gene regulatory networks.

    PubMed

    Baumbach, Jan

    2010-12-01

    The National Center for Biotechnology Information (NCBI) recently announced '1000 prokaryotic genomes are now completed and available in the Genome database'. The increasing trend will provide us with thousands of sequenced microbial organisms over the next years. However, this is only the first step in understanding how cells survive, reproduce and adapt their behavior while being exposed to changing environmental conditions. One major control mechanism is transcriptional gene regulation. Here, striking is the direct juxtaposition of the handful of bacterial model organisms to the 1000 prokaryotic genomes. Next-generation sequencing technologies will further widen this gap drastically. However, several computational approaches have proven to be helpful. The main idea is to use the known transcriptional regulatory network of reference organisms as template in order to unravel evolutionarily conserved gene regulations in newly sequenced species. This transfer essentially depends on the reliable identification of several types of conserved DNA sequences. We decompose this problem into three computational processes, review the state of the art and illustrate future perspectives.

  1. Predicting conserved essential genes in bacteria: in silico identification of putative drug targets.

    PubMed

    Duffield, Melanie; Cooper, Ian; McAlister, Erin; Bayliss, Marc; Ford, Donna; Oyston, Petra

    2010-12-01

    Many genes have been listed as putatively essential for bacterial viability in the Database of Essential Genomes (DEG), although few have been experimentally validated. By prioritising targets according to the criteria suggested by the Research and Training in Tropical Diseases (TDR) Targets database, we have developed a modified down-selection tool to identify essential genes conserved across diverse genera. Using this approach we identified 52 proteins conserved to 7 or more of the 14 genomes in DEG. We confirmed the validity of the down-selection by attempting to make mutants of 8 of these targets in a model organism, Yersinia pseudotuberculosis, which is not closely related to any of the bacteria in DEG. Mutants were recovered for only one of the 8 targets, suggesting that the other 7 were essential in Y. pseudotuberculosis, an impressive success rate compared to other approaches of identification for such targets. Identification of essential proteins common in diverse bacterial genera can then be used to facilitate the selection of effective targets for novel broad-spectrum antibiotics.

  2. The human archain gene, ARCN1, has highly conserved homologs in rice and drosophila

    SciTech Connect

    Radice, P.; Jones, C.; Perry, H.

    1995-03-01

    A novel human gene, ARCN1, has been identified in chromosome band 11q23.3. It maps approximately 50 kb telomeric to MLL, a gene that is disrupted in a number of leukemia-associated translocation chromosomes. cDNA clones representing ARCN1 hybridize to 4-kb mRNA species present in all tissues tested. Sequencing of cDNAs suggests that at least two forms of mRNA with alternative 5 {prime} ends are present within the cell. The mRNA with the longest open reading frame gives rise to a protein of 57 kDa. Although the sequence reported is novel, remarkable similarity is observed with two predicted protein sequences from partial DNA sequences generated by rice (Oryza sativa) and fruit fly (Drosophila melanogaster) genome projects. The degree of sequence conservation is comparable to that observed for highly conserved structural proteins, such as heat shock protein HSP70, and is greater than that of {gamma}-gubulin and heat shock protein HSP60. A more distant relationship to the group of clathrin-associated proteins suggests a possible role in vesicle structure or trafficking. In view of its ancient pedigree and a potential involvement in cellular architecture, the authors propose that the ARCN1 protein be named archain. 20 refs., 5 figs.

  3. Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals.

    PubMed

    Türeci, Ozlem; Koslowski, Michael; Helftenbein, Gerd; Castle, John; Rohde, Christoph; Dhaene, Karl; Seitz, Gerhard; Sahin, Ugur

    2011-08-01

    Claudin-18 isoform 2 (CLDN18.2) is one of the few members of the human claudin family of tight junction molecules with strict restriction to one cell lineage. The objective of the current study was to compare molecular structure and tissue distribution of this gastrocyte specific molecule in mammals. We show here that the CLDN18.2 protein sequence is highly conserved, in particular with regard to functionally relevant domains in mouse, rat, rabbit, dog, monkey and human and also in lizards. Moreover, promoter regions of orthologs are highly homologous, including the binding site of the transcription factor cyclic AMP-responsive element binding protein (CREB), which is known to regulate activation of human CLDN18.2. Employing RT-PCR and immunohistochemistry, we found that, analogous to the human gene, all orthologous CLDN18.2 transcripts and proteins are exclusively expressed in differentiated gastric cells. Gene structure, promoter elements and RNA expression pattern of the lung-tissue specific Claudin-18 isoform 1 (CLDN18.1) as well, are homologous across species. These findings exemplify phylogenetic conservation of lineage-specific members of a multigene family. Given that CLDN18.2 is a novel drug target candidate, our data is also relevant for drug development as it reveals all six investigated mammalian species as suitable models for testing safety of CLDN18.2 targeting regimen.

  4. Cryptorchidism and testicular cancer.

    PubMed

    Batata, M A; Whitmore, W F; Chu, F C; Hilaris, B S; Loh, J; Grabstald, H; Golbey, R

    1980-09-01

    An analysis of 125 patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor treated at our hospital from 1934 to 1975 is presented. Cryptorchidism was corrected ipsilaterally or contralaterally in 83 patients with intrascrotal testis cancer when they were from 4 to 42 years old, either spontaneously (21 patients), by orchiopexy (51 patients) or by hormonal therapy (11 patients). Forty-two cryptorchid patients (uncorrected cases) presented with either ipsilateral inguinal (24 patients), abdominal (14 patients) or contralateral intrascrotal tumors (4 patients). Tumor histologic types on orchiectomy were pure seminoma in 54 patients, embryonal carcinoma in 35, teratocarcinoma in 33 and pure choriocarcinoma in 3. The 5-year survival rates were 60 per cent for the corrected cases and 63 per cent for the uncorrected cases according to cryptorchid state, and they were 78 per cent in patients with pure seminoma and 48 per cent in patients with other germinomas according to histologic type. The majority (58 of 73) of 5-year survivors received regional lymphatic irradiation, in 39 patients with pure seminoma, and/or systemic chemotherapy, in 19 patients with germinal carcinomas, with or without regional lymphadenectomy.

  5. Polymerase Chain Reaction (PCR)-based methods for detection and identification of mycotoxigenic Penicillium species using conserved genes

    USDA-ARS?s Scientific Manuscript database

    Polymerase chain reaction amplification of conserved genes and sequence analysis provides a very powerful tool for the identification of toxigenic as well as non-toxigenic Penicillium species. Sequences are obtained by amplification of the gene fragment, sequencing via capillary electrophoresis of d...

  6. Conserved Curvature of RNA Polymerase I Core Promoter Beyond rRNA Genes: The Case of the Tritryps

    PubMed Central

    Smircich, Pablo; Duhagon, María Ana; Garat, Beatriz

    2015-01-01

    In trypanosomatids, the RNA polymerase I (RNAPI)-dependent promoters controlling the ribosomal RNA (rRNA) genes have been well identified. Although the RNAPI transcription machinery recognizes the DNA conformation instead of the DNA sequence of promoters, no conformational study has been reported for these promoters. Here we present the in silico analysis of the intrinsic DNA curvature of the rRNA gene core promoters in Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major. We found that, in spite of the absence of sequence conservation, these promoters hold conformational properties similar to other eukaryotic rRNA promoters. Our results also indicated that the intrinsic DNA curvature pattern is conserved within the Leishmania genus and also among strains of T. cruzi and T. brucei. Furthermore, we analyzed the impact of point mutations on the intrinsic curvature and their impact on the promoter activity. Furthermore, we found that the core promoters of protein-coding genes transcribed by RNAPI in T. brucei show the same conserved conformational characteristics. Overall, our results indicate that DNA intrinsic curvature of the rRNA gene core promoters is conserved in these ancient eukaryotes and such conserved curvature might be a requirement of RNAPI machinery for transcription of not only rRNA genes but also protein-coding genes. PMID:26718450

  7. [Epididymal and testicular chronic pain].

    PubMed

    Sibert, L; Safsaf, A; Rigaud, J; Delavierre, D; Labat, J-J

    2010-11-01

    To list clinical and ethiopathogenical elements relevant to the analysis of an epididymal and testicular pain. Review of published articles on the subject in the Medline(®) (PubMed(®)) database, selected according to their scientific relevance. Assessment of a chronic epididymal and testicular pain is mostly clinical and should: (1) eliminate local urological disorder; (2) suggest a neurological problem, based on signs and semiology; (3) suggest injury of nervous truncus according to medical history and scars; (4) detect referred pains, primarily back and thoracolumbar pains. The causal link between epididymal cysts, surgical aftereffect, local infection and chronic epididymal and testicular pain is not established with certainty. Spermatic cord nerve block, as a diagnostic test, should be done before undergoing any invasive procedure. The fundamental notion is being able to distinguish epididymal and testicular pain and scrotal pain, because the testis has an abdominal origin, and therefore a sympathetic instead of sacral innervation. An absence evident somatic or iatrogenous cause should suggest hypersensibility to pain. Assessment of an epididymal and testicular pain requires a global clinical examination, which should take into account every aspect of the pain, including its functional and emotional components. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  8. [Testicular torsion: A case report].

    PubMed

    García-Fernández, Gustavo; Bravo-Hernández, Alberto; Bautista-Cruz, Raúl

    2016-07-13

    The acute scrotum is an emergency. Testicular torsion represents approximately 25% of the causes. The annual incidence of testicular torsion is approximately 1/4,000 persons under 25 years, with highest prevalence between 12 and 18 years old. It usually occurs without apparent cause, but it has been associated with anatomical, traumatic, and environmental factors, among others. A male 15 year-old male, with no history of importance, was seen in the Emergency Department, presenting with a sudden and continuous pain in the left testicle. It was accompanied by a pain that radiated to the abdomen and left inguinal area, with nausea and vomiting of more than 12h onset. Doppler ultrasound showed changes suggestive of testicular torsion. Surgery was performed that showed findings of a necrotic left testicle with rotation of the spermatic cord of 360°. A left orchiectomy was performed. Testicular torsion should always be considered one of the leading causes of acute scrotal pain. Delays in diagnosis should be avoided as this is directly related to the percentage of testicular salvage or loss. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Structural but not functional conservation of an immune molecule: a tachylectin-like gene in Hydractinia.

    PubMed

    Mali, Brahim; Soza-Ried, Jorge; Frohme, Marcus; Frank, Uri

    2006-01-01

    Tachylectin-related proteins are a recently characterized group of pattern recognition molecules, functioning in the innate immunity of various animals, from the ancient sponges to vertebrates. Tachylectins are characterized by six internal tandem repeats forming beta-propeller domains. We have identified and characterized a tachylectin-related gene in the colonial marine hydroid, Hydractinia echinata. The predicted gene product, termed CTRN, contained an N-terminal signal peptide and had a well-conserved tachylectin-like structure. RT-PCR analyses revealed only post-metamorphic expression while no mRNA was detected during embryonic development or in planula larvae. Exposure of colonies to LPS under conditions known to activate an immune response in Hydractinia did not result in upregulation of the gene. In situ hybridization analysis of metamorphosed animals detected CTRN transcripts only in a small subpopulation of neurons and their precursor cells, localized in a ring-like structure around the mouth of polyps. The same ring-like structure of CTRN expressing neurons was also observed in young polyp buds, predicting the position of the future mouth. This type of expression pattern can hardly be attributed to an immune-relevant gene. Thus, despite high structural similarity to tachylectins, this cnidarian member of this group seems to be an exception to all other tachylectins identified so far as it seems to have no function in cnidarian innate immunity.

  10. Conservation, Duplication, and Divergence of Five Opsin Genes in Insect Evolution

    PubMed Central

    Feuda, Roberto; Marlétaz, Ferdinand; Bentley, Michael A.; Holland, Peter W.H.

    2016-01-01

    Opsin proteins covalently bind to small molecular chromophores and each protein-chromophore complex is sensitive to particular wavelengths of light. Multiple opsins with different wavelength absorbance peaks are required for color vision. Comparing opsin responses is challenging at low light levels, explaining why color vision is often lost in nocturnal species. Here, we investigated opsin evolution in 27 phylogenetically diverse insect species including several transitions between photic niches (nocturnal, diurnal, and crepuscular). We find widespread conservation of five distinct opsin genes, more than commonly considered. These comprise one c-opsin plus four r-opsins (long wavelength sensitive or LWS, blue sensitive, ultra violet [UV] sensitive and the often overlooked Rh7 gene). Several recent opsin gene duplications are also detected. The diversity of opsin genes is consistent with color vision in diurnal, crepuscular, and nocturnal insects. Tests for positive selection in relation to photic niche reveal evidence for adaptive evolution in UV-sensitive opsins in day-flying insects in general, and in LWS opsins of day-flying Lepidoptera specifically. PMID:26865071

  11. [Bioinformatic prediction of conserved microRNAs and their target genes in eggplant (Solanum melongena L.)].

    PubMed

    Zhang, Lei; Chao, Jiang-Tao; Cui, Meng-Meng; Chen, Ya-Qiong; Zong, Peng; Sun, Yu-He

    2011-07-01

    MicroRNAs (miRNAs), a recently discovered class of small (-21nt), non-coding, endogenous, single-stranded RNAs in eukaryotes, regulate gene expression negatively at the post-transcriptional levels depending on the extent of complementation between miRNA and mRNA. To date, a large number of miRNAs have been reported in many species, but none for eggplant (Solanum melongena L.). In this paper, a computational homology search approach based on the conservation of miRNA sequences and the stem-loop hairpin secondary structures of miRNAs was adopted. The search was started with the known plant miRNAs compared to eggplant expressed sequence tags (EST) databases to find potential miRNAs. Following a range of filtering criteria, a total of 16 potential miRNAs belonging to 12 families were identified. Three pairs of sense and antisense strand eggplant miRNAs belonging to three different miRNA families were also found. Furthermore, miR390 and miR399 sense/antisense pairs are identified for the first time in plants. Using online software psRNATarget, we further predicted the target genes of these 16 miRNAs and got 71 potential targets genes on base of 15 eggplant miRNAs. Most of these target genes were predicted to encode proteins that play key role in eggplant growth, development, metabolism, and stress responses.

  12. SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature

    PubMed Central

    Sandoval, Gloria Tatiana Vinasco; Jaimes, Giovanna Carola; Barrios, Mauricio Coll; Cespedes, Camila; Velasco, Harvy Mauricio

    2014-01-01

    SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate short stature (DSS). However, this gene has also been found to be mutated in cases of idiopathic short stature (ISS) with a 3–15% frequency. In this study, the multiplex ligation-dependent probe amplification (MLPA) technique was employed to determine the frequency of SHOX gene mutations and their conserved noncoding elements (CNE) in Colombian patients with ISS. Patients were referred from different centers around the county. From a sample of 62 patients, 8.1% deletions and insertions in the intragenic regions and in the CNE were found. This result is similar to others published in other countries. Moreover, an isolated case of CNE 9 duplication and a new intron 6b deletion in another patient, associated with ISS, are described. This is one of the first studies of a Latin American population in which deletions/duplications of the SHOX gene and its CNE are examined in patients with ISS. PMID:24689071

  13. Conservation, Duplication, and Divergence of Five Opsin Genes in Insect Evolution.

    PubMed

    Feuda, Roberto; Marlétaz, Ferdinand; Bentley, Michael A; Holland, Peter W H

    2016-02-09

    Opsin proteins covalently bind to small molecular chromophores and each protein-chromophore complex is sensitive to particular wavelengths of light. Multiple opsins with different wavelength absorbance peaks are required for color vision. Comparing opsin responses is challenging at low light levels, explaining why color vision is often lost in nocturnal species. Here, we investigated opsin evolution in 27 phylogenetically diverse insect species including several transitions between photic niches (nocturnal, diurnal, and crepuscular). We find widespread conservation of five distinct opsin genes, more than commonly considered. These comprise one c-opsin plus four r-opsins (long wavelength sensitive or LWS, blue sensitive, ultra violet [UV] sensitive and the often overlooked Rh7 gene). Several recent opsin gene duplications are also detected. The diversity of opsin genes is consistent with color vision in diurnal, crepuscular, and nocturnal insects. Tests for positive selection in relation to photic niche reveal evidence for adaptive evolution in UV-sensitive opsins in day-flying insects in general, and in LWS opsins of day-flying Lepidoptera specifically. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13.

    PubMed

    Streit, Adrian; Kohler, Reto; Marty, Thomas; Belfiore, Marco; Takacs-Vellai, Krisztina; Vigano, Maria-Alessandra; Schnabel, Ralf; Affolter, Markus; Müller, Fritz

    2002-02-15

    Caenorhabditis elegans contains a set of six cluster-type homeobox (Hox) genes that are required during larval development. Some of them, but unlike in flies not all of them, are also required during embryogenesis. It has been suggested that the control of the embryonic expression of the worm Hox genes might differ from that of other species by being regulated in a lineal rather than a regional mode. Here, we present a trans-species analysis of the cis-regulatory region of ceh-13, the worm ortholog of the Drosophila labial and the vertebrate Hox1 genes, and find that the molecular mechanisms that regulate its expression may be similar to what has been found in species that follow a regulative, non-cell-autonomous mode of development. We have identified two enhancer fragments that are involved in different aspects of the embryonic ceh-13 expression pattern. We show that important features of comma-stage expression depend on an autoregulatory input that requires ceh-13 and ceh-20 functions. Our data show that the molecular nature of Hox1 class gene autoregulation has been conserved between worms, flies, and vertebrates. The second regulatory sequence is sufficient to drive correct early embryonic expression of ceh-13. Interestingly, this enhancer fragment acts as a response element of the Wnt/WG signaling pathway in Drosophila embryos.

  15. Physical mapping of the elephant X chromosome: conservation of gene order over 105 million years.

    PubMed

    Delgado, Claudia Leticia Rodríguez; Waters, Paul D; Gilbert, Clément; Robinson, Terence J; Graves, Jennifer A Marshall

    2009-01-01

    All therian mammals (eutherians and marsupials) have an XX female/XY male sex chromosome system or some variant of it. The X and Y evolved from a homologous pair of autosomes over the 166 million years since therian mammals diverged from monotremes. Comparing the sex chromosomes of eutherians and marsupials defined an ancient X conserved region that is shared between species of these mammalian clades. However, the eutherian X (and the Y) was augmented by a recent addition (XAR) that is autosomal in marsupials. XAR is part of the X in primates, rodents, and artiodactyls (which belong to the eutherian clade Boreoeutheria), but it is uncertain whether XAR is part of the X chromosome in more distantly related eutherian mammals. Here we report on the gene content and order on the X of the elephant (Loxodonta africana)-a representative of Afrotheria, a basal endemic clade of African mammals-and compare these findings to those of other documented eutherian species. A total of 17 genes were mapped to the elephant X chromosome. Our results support the hypothesis that the eutherian X and Y chromosomes were augmented by the addition of autosomal material prior to eutherian radiation. Not only does the elephant X bear the same suite of genes as other eutherian X chromosomes, but gene order appears to have been maintained across 105 million years of evolution, perhaps reflecting strong constraints posed by the eutherian X inactivation system.

  16. Conservation in the involvement of heterochronic genes and hormones during developmental transitions.

    PubMed

    Faunes, Fernando; Larraín, Juan

    2016-08-01

    Developmental transitions include molting in some invertebrates and the metamorphosis of insects and amphibians. While the study of Caenorhabditis elegans larval transitions was crucial to determine the genetic control of these transitions, Drosophila melanogaster and Xenopus laevis have been classic models to study the role of hormones in metamorphosis. Here we review how heterochronic genes (lin-4, let-7, lin-28, lin-41), hormones (dafachronic acid, ecdysone, thyroid hormone) and the environment regulate developmental transitions. Recent evidence suggests that some heterochronic genes also regulate transitions in higher organisms that they are controlled by hormones involved in metamorphosis. We also discuss evidence demonstrating that heterochronic genes and hormones regulate the proliferation and differentiation of embryonic and neural stem cells. We propose the hypothesis that developmental transitions are regulated by an evolutionary conserved mechanism in which heterochronic genes and hormones interact to control stem/progenitor cells proliferation, cell cycle exit, quiescence and differentiation and determine the proper timing of developmental transitions. Finally, we discuss the relevance of these studies to understand post-embryonic development, puberty and regeneration in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution.

    PubMed

    Otto, Edgar; Hoefele, Julia; Ruf, Rainer; Mueller, Adelheid M; Hiller, Karl S; Wolf, Matthias T F; Schuermann, Maria J; Becker, Achim; Birkenhäger, Ralf; Sudbrak, Ralf; Hennies, Hans C; Nürnberg, Peter; Hildebrandt, Friedhelm

    2002-11-01

    Nephronophthisis (NPHP) comprises a group of autosomal recessive cystic kidney diseases, which constitute the most frequent genetic cause for end-stage renal failure in children and young adults. The most prominent histologic feature of NPHP consists of development of renal fibrosis, which, in chronic renal failure of any origin, represents the pathogenic event correlated most strongly to loss of renal function. Four gene loci for NPHP have been mapped to chromosomes 2q13 (NPHP1), 9q22 (NPHP2), 3q22 (NPHP3), and 1p36 (NPHP4). At all four loci, linkage has also been demonstrated in families with the association of NPHP and retinitis pigmentosa, known as "Senior-Løken syndrome" (SLS). Identification of the gene for NPHP type 1 had revealed nephrocystin as a novel docking protein, providing new insights into mechanisms of cell-cell and cell-matrix signaling. We here report identification of the gene (NPHP4) causing NPHP type 4, by use of high-resolution haplotype analysis and by demonstration of nine likely loss-of-function mutations in six affected families. NPHP4 encodes a novel protein, nephroretinin, that is conserved in evolution--for example, in the nematode Caenorhabditis elegans. In addition, we demonstrate two loss-of-function mutations of NPHP4 in patients from two families with SLS. Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function.

  18. Sphingolipids, Transcription Factors, and Conserved Toolkit Genes: Developmental Plasticity in the Ant Cardiocondyla obscurior

    PubMed Central

    Schrader, Lukas; Simola, Daniel F.; Heinze, Jürgen; Oettler, Jan

    2015-01-01

    Developmental plasticity allows for the remarkable morphological specialization of individuals into castes in eusocial species of Hymenoptera. Developmental trajectories that lead to alternative caste fates are typically determined by specific environmental stimuli that induce larvae to express and maintain distinct gene expression patterns. Although most eusocial species express two castes, queens and workers, the ant Cardiocondyla obscurior expresses diphenic females and males; this provides a unique system with four discrete phenotypes to study the genomic basis of developmental plasticity in ants. We sequenced and analyzed the transcriptomes of 28 individual C. obscurior larvae of known developmental trajectory, providing the first in-depth analysis of gene expression in eusocial insect larvae. Clustering and transcription factor binding site analyses revealed that different transcription factors and functionally distinct sets of genes are recruited during larval development to induce the four alternative trajectories. In particular, we found complex patterns of gene regulation pertaining to sphingolipid metabolism, a conserved molecular pathway involved in development, obesity, and aging. PMID:25725431

  19. Conservation of Arabidopsis thaliana photoperiodic flowering time genes in onion (Allium cepa L.).

    PubMed

    Taylor, Andrew; Massiah, Andrea Juliet; Thomas, Brian

    2010-10-01

    The genetics underlying onion development are poorly understood. Here the characterization of onion homologs of Arabidopsis photoperiodic flowering pathway genes is reported with the end goal of accelerating onion breeding programs by understanding the genetic basis of adaptation to different latitudes. The expression of onion GI, FKF1 and ZTL homologs under short day (SD) and long day (LD) conditions was examined using quantitative reverse transcription-PCR (qRT-PCR). The expression of AcGI and AcFKF1 was examined in onion varieties which exhibit different daylength responses. Phylogenetic trees were constructed to confirm the identity of the homologs. AcGI and AcFKF1 showed diurnal expression patterns similar to their Arabidopsis counterparts, while AcZTL was found to be constitutively expressed. AcGI showed similar expression patterns in varieties which exhibit different daylength responses, whereas AcFKF1 showed differences. It is proposed that these differences could contribute to the different daylength responses in these varieties. Phylogenetic analyses showed that all the genes isolated are very closely related to their proposed homologs. The results presented here show that key genes controlling photoperiodic flowering in Arabidopsis are conserved in onion, and a role for these genes in the photoperiodic control of bulb initiation is predicted. This theory is supported by expression and phylogenetic data.

  20. Conservation of gene order between horse and human X chromosomes as evidenced through radiation hybrid mapping.

    PubMed

    Raudsepp, Terje; Kata, Srinivas R; Piumi, François; Swinburne, June; Womack, James E; Skow, Loren C; Chowdhary, Bhanu P

    2002-03-01

    A radiation hybrid (RH) map of the equine X chromosome (ECAX) was obtained using the recently produced 5000(rad) horse x hamster hybrid panel. The map comprises 34 markers (16 genes and 18 microsatellites) and spans a total of 676 cR(5000), covering almost the entire length of ECAX. Cytogenetic alignment of the RH map was improved by fluorescent in situ hybridization mapping of six of the markers. The map integrates and refines the currently available genetic linkage, syntenic, and cytogenetic maps, and adds new loci. Comparison of the physical location of the 16 genes mapped in this study with the human genome reveals similarity in the order of the genes along the entire length of the two X chromosomes. This degree of gene order conservation across evolutionarily distantly related species has up to now been reported only between human and cat. The ECAX RH map provides a framework for the generation of a high-density map for this chromosome. The map will serve as an important tool for positional cloning of X-linked diseases/conditions in the horse.

  1. Structural complexity and evolutionary conservation of the Drosophila homeotic gene proboscipedia.

    PubMed Central

    Cribbs, D L; Pultz, M A; Johnson, D; Mazzulla, M; Kaufman, T C

    1992-01-01

    Mutations of the homeotic gene proboscipedia (pb) of Drosophila cause striking transformations of the adult mouthparts, to legs or antennae. We report here an analysis of the gene structure of pb. Coding sequences across a 34 kb interval yield, by alternative splicing, four identified mRNA forms which differ immediately upstream of the homeobox. As a consequence, the homeodomain is expected to reside in four different contexts in the predicted protein isoforms. Mammalian homologs of pb, human HOX-2H and murine Hox-2.8, were identified based on the similarities of their homeodomains (95% identity) and several other conserved motifs. Examination of a collection of pb mutant alleles with antisera directed against the N-terminal region, the center or the C-terminal region of the protein showed that, surprisingly, several partial loss-of-function pb alleles appear to generate partially functional proteins truncated at their C-termini. This suggests that a significant portion of the protein contributes quantitatively to pb function, but is partially dispensable. Finally, evolutionary considerations suggest that pb may be one of several ancient genes which preceded the process yielding the modern homeotic gene complexes. Images PMID:1348688

  2. Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells.

    PubMed

    Akingbemi, Benson T; Sottas, Chantal M; Koulova, Anna I; Klinefelter, Gary R; Hardy, Matthew P

    2004-02-01

    Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 microg/kg.d (a dose that approximates BPA levels in the environment) from postnatal d 21-35 suppressed serum LH (0.21 +/- 0.05 ng/ml; vs. control, 0.52 +/- 0.04; P < 0.01) and testosterone (T) levels (1.62 +/- 0.16 ng/ml; vs. control, 2.52 +/- 0.21; P < 0.05), in association with decreased LHbeta and increased estrogen receptor beta pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17alpha-hydroxylase/17-20 lyase. BPA decreased serum 17beta-estradiol levels from 0.31 +/- 0.02 ng/ml (control) to 0.22 +/- 0.02, 0.19 +/- 0.02, and 0.23 +/- 0.03 ng/ml in rats exposed to 2.4 microg, 10 microg, or 100 mg/kg.d BPA, respectively, from 21-35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 +/- 34 (control) to 261 +/- 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.

  3. Genes of the most conserved WOX clade in plants affect root and flower development in Arabidopsis

    PubMed Central

    2008-01-01

    Background The Wuschel related homeobox (WOX) family proteins are key regulators implicated in the determination of cell fate in plants by preventing cell differentiation. A recent WOX phylogeny, based on WOX homeodomains, showed that all of the Physcomitrella patens and Selaginella moellendorffii WOX proteins clustered into a single orthologous group. We hypothesized that members of this group might preferentially share a significant part of their function in phylogenetically distant organisms. Hence, we first validated the limits of the WOX13 orthologous group (WOX13 OG) using the occurrence of other clade specific signatures and conserved intron insertion sites. Secondly, a functional analysis using expression data and mutants was undertaken. Results The WOX13 OG contained the most conserved plant WOX proteins including the only WOX detected in the highly proliferating basal unicellular and photosynthetic organism Ostreococcus tauri. A large expansion of the WOX family was observed after the separation of mosses from other land plants and before monocots and dicots have arisen. In Arabidopsis thaliana, AtWOX13 was dynamically expressed during primary and lateral root initiation and development, in gynoecium and during embryo development. AtWOX13 appeared to affect the floral transition. An intriguing clade, represented by the functional AtWOX14 gene inside the WOX13 OG, was only found in the Brassicaceae. Compared to AtWOX13, the gene expression profile of AtWOX14 was restricted to the early stages of lateral root formation and specific to developing anthers. A mutational insertion upstream of the AtWOX14 homeodomain sequence led to abnormal root development, a delay in the floral transition and premature anther differentiation. Conclusion Our data provide evidence in favor of the WOX13 OG as the clade containing the most conserved WOX genes and established a functional link to organ initiation and development in Arabidopsis, most likely by preventing premature

  4. Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

    PubMed Central

    Lopez, Lorna M; Harris, Sarah E; Luciano, Michelle; Liewald, Dave; Davies, Gail; Gow, Alan J; Tenesa, Albert; Payton, Antony; Ke, Xiayi; Whalley, Lawrence J; Fox, Helen; Haggerty, Paul; Ollier, William; Pickles, Andrew; Porteous, David J; Horan, Michael A; Pendleton, Neil; Starr, John M; Deary, Ian J

    2012-01-01

    Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. PMID:22045296

  5. Redeployment of a conserved gene regulatory network during Aedes aegypti development.

    PubMed

    Suryamohan, Kushal; Hanson, Casey; Andrews, Emily; Sinha, Saurabh; Scheel, Molly Duman; Halfon, Marc S

    2016-08-15

    Changes in gene regulatory networks (GRNs) underlie the evolution of morphological novelty and developmental system drift. The fruitfly Drosophila melanogaster and the dengue and Zika vector mosquito Aedes aegypti have substantially similar nervous system morphology. Nevertheless, they show significant divergence in a set of genes co-expressed in the midline of the Drosophila central nervous system, including the master regulator single minded and downstream genes including short gastrulation, Star, and NetrinA. In contrast to Drosophila, we find that midline expression of these genes is either absent or severely diminished in A. aegypti. Instead, they are co-expressed in the lateral nervous system. This suggests that in A. aegypti this "midline GRN" has been redeployed to a new location while lost from its previous site of activity. In order to characterize the relevant GRNs, we employed the SCRMshaw method we previously developed to identify transcriptional cis-regulatory modules in both species. Analysis of these regulatory sequences in transgenic Drosophila suggests that the altered gene expression observed in A. aegypti is the result of trans-dependent redeployment of the GRN, potentially stemming from cis-mediated changes in the expression of sim and other as-yet unidentified regulators. Our results illustrate a novel "repeal, replace, and redeploy" mode of evolution in which a conserved GRN acquires a different function at a new site while its original function is co-opted by a different GRN. This represents a striking example of developmental system drift in which the dramatic shift in gene expression does not result in gross morphological changes, but in more subtle differences in development and function of the late embryonic nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Redeployment of a conserved gene regulatory network during Aedes aegypti development

    PubMed Central

    Suryamohan, Kushal; Hanson, Casey; Andrews, Emily; Sinha, Saurabh; Scheel, Molly Duman; Halfon, Marc S.

    2016-01-01

    Changes in gene regulatory networks (GRNs) underlie the evolution of morphological novelty and developmental system drift. The fruitfly Drosophila melanogaster and the dengue and Zika vector mosquito Aedes aegypti have substantially similar nervous system morphology. Nevertheless, they show significant divergence in a set of genes co-expressed in the midline of the Drosophila central nervous system, including the master regulator single minded and downstream genes including short gastrulation, Star, and NetrinA. In contrast to Drosophila, we find that midline expression of these genes is either absent or severely diminished in A. aegypti. Instead, they are co-expressed in the lateral nervous system. This suggests that in A. aegypti this “midline GRN” has been redeployed to a new location while lost from its previous site of activity. In order to characterize the relevant GRNs, we employed the SCRMshaw method we previously developed to identify transcriptional cis-regulatory modules in both species. Analysis of these regulatory sequences in transgenic Drosophila suggests that the altered gene expression observed in A. aegypti is the result of trans-dependent redeployment of the GRN, potentially stemming from cis-mediated changes in the expression of sim and other as-yet unidentified regulators. Our results illustrate a novel “repeal, replace, and redeploy” mode of evolution in which a conserved GRN acquires a different function at a new site while its original function is co-opted by a different GRN. This represents a striking example of developmental system drift in which the dramatic shift in gene expression does not result in gross morphological changes, but in more subtle differences in development and function of the late embryonic nervous system. PMID:27341759

  7. 21 CFR 876.3750 - Testicular prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Testicular prosthesis. 876.3750 Section 876.3750...) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3750 Testicular prosthesis. (a) Identification. A testicular prosthesis is an implanted device that consists of a solid or gel-filled...

  8. 21 CFR 876.3750 - Testicular prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Testicular prosthesis. 876.3750 Section 876.3750...) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3750 Testicular prosthesis. (a) Identification. A testicular prosthesis is an implanted device that consists of a solid or gel-filled...

  9. 21 CFR 876.3750 - Testicular prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Testicular prosthesis. 876.3750 Section 876.3750...) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3750 Testicular prosthesis. (a) Identification. A testicular prosthesis is an implanted device that consists of a solid or gel-filled...

  10. Regulatory conservation of protein coding and microRNA genes in vertebrates: lessons from the opossum genome.

    PubMed

    Mahony, Shaun; Corcoran, David L; Feingold, Eleanor; Benos, Panayiotis V

    2007-01-01

    Being the first noneutherian mammal sequenced, Monodelphis domestica (opossum) offers great potential for enhancing our understanding of the evolutionary processes that take place in mammals. This study focuses on the evolutionary relationships between conservation of noncoding sequences, cis-regulatory elements, and biologic functions of regulated genes in opossum and eight vertebrate species. Analysis of 145 intergenic microRNA and all protein coding genes revealed that the upstream sequences of the former are up to twice as conserved as the latter among mammals, except in the first 500 base pairs, where the conservation is similar. Comparison of promoter conservation in 513 protein coding genes and related transcription factor binding sites (TFBSs) showed that 41% of the known human TFBSs are located in the 6.7% of promoter regions that are conserved between human and opossum. Some core biologic processes exhibited significantly fewer conserved TFBSs in human-opossum comparisons, suggesting greater functional divergence. A new measure of efficiency in multigenome phylogenetic footprinting (base regulatory potential rate [BRPR]) shows that including human-opossum conservation increases specificity in finding human TFBSs. Opossum facilitates better estimation of promoter conservation and TFBS turnover among mammals. The fact that substantial TFBS numbers are located in a small proportion of the human-opossum conserved sequences emphasizes the importance of marsupial genomes for phylogenetic footprinting-based motif discovery strategies. The BRPR measure is expected to help select genome combinations for optimal performance of these algorithms. Finally, although the etiology of the microRNA upstream increased conservation remains unknown, it is expected to have strong implications for our understanding of regulation of their expression.

  11. Conservation of symbiotic nitrogen fixation gene sequences in Rhizobium japonicum and Bradyrhizobium japonicum.

    PubMed Central

    Masterson, R V; Prakash, R K; Atherly, A G

    1985-01-01

    Southern hybridization with nif (nitrogen fixation) and nod (nodulation) DNA probes from Rhizobium meliloti against intact plasmid DNA of Rhizobium japonicum and Bradyrhizobium japonicum strains indicated that both nif and nod sequences are on plasmid DNA in most R. japonicum strains. An exception is found with R. japonicum strain USDA194 and all B. japonicum strains where nif and nod sequences are on the chromosome. In R. japonicum strains, with the exception of strain USDA205, both nif and nod sequences are on the same plasmid. In strain USDA205, the nif genes are on a 112-megadalton plasmid, and nod genes are on a 195-megadalton plasmid. Hybridization to EcoRI digests of total DNA to nif and nod probes from R. meliloti show that the nif and nod sequences are conserved in both R. japonicum and B. japonicum strains regardless of the plasmid or chromosomal location of these genes. In addition, nif DNA hybridization patterns were identical among all R. japonicum strains and with most of the B. japonicum strains examined. Similarly, many of the bands that hybridize to the nodulation probe isolated from R. meliloti were found to be common among R. japonicum strains. Under reduced hybridization stringency conditions, strong conservation of nodulation sequences was observed in strains of B. japonicum. We have also found that the plasmid pRjaUSDA193, which possess nif and nod sequences, does not possess sequence homology with any plasmid of USDA194, but is homologous to parts of the chromosome of USDA194. Strain USDA194 is unique, since nif and nod sequences are present on the chromosome instead of on a plasmid as observed with all other strains examined. Images PMID:4008441

  12. Gene expression suggests conserved aspects of Hox gene regulation in arthropods and provides additional support for monophyletic Myriapoda.

    PubMed

    Janssen, Ralf; Budd, Graham E

    2010-07-05

    Antisense transcripts of Ultrabithorax (aUbx) in the millipede Glomeris and the centipede Lithobius are expressed in patterns complementary to that of the Ubx sense transcripts. A similar complementary expression pattern has been described for non-coding RNAs (ncRNAs) of the bithoraxoid (bxd) locus in Drosophila, in which the transcription of bxd ncRNAs represses Ubx via transcriptional interference. We discuss our findings in the context of possibly conserved mechanisms of Ubx regulation in myriapods and the fly.Bicistronic transcription of Ubx and Antennapedia (Antp) has been reported previously for a myriapod and a number of crustaceans. In this paper, we show that Ubx/Antp bicistronic transcripts also occur in Glomeris and an onychophoran, suggesting further conserved mechanisms of Hox gene regulation in arthropods.Myriapod monophyly is supported by the expression of aUbx in all investigated myriapods, whereas in other arthropod classes, including the Onychophora, aUbx is not expressed. Of the two splice variants of Ubx/Antp only one could be isolated from myriapods, representing a possible further synapomorphy of the Myriapoda.

  13. Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

    PubMed Central

    Lü, M; Tian, H; Cao, Y-x; He, X; Chen, L; Song, X; Ping, P; Huang, H; Sun, F

    2015-01-01

    Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1-C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis. PMID:26539909

  14. Contribution of IL-12/IL-35 Common Subunit p35 to Maintaining the Testicular Immune Privilege

    PubMed Central

    Terayama, Hayato; Yoshimoto, Takayuki; Hirai, Shuichi; Naito, Munekazu; Qu, Ning; Hatayama, Naoyuki; Hayashi, Shogo; Mitobe, Kana; Furusawa, Jun-ichi; Mizoguchi, Izuru; Kezuka, Takeshi; Goto, Hiroshi; Suyama, Kaori; Moriyama, Hiroshi; Sakabe, Kou; Itoh, Masahiro

    2014-01-01

    The testis is an organ with immune privilege. The comprehensive blood–testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body’s immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus−induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various immune responses, but their roles in testicular immune privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular immune privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular immune privilege, in part in an IL-35-dependent manner. PMID:24760014

  15. A stationary-phase gene in Saccharomyces cerevisiae is a member of a novel, highly conserved gene family.

    PubMed Central

    Braun, E L; Fuge, E K; Padilla, P A; Werner-Washburne, M

    1996-01-01

    The regulation of cellular growth and proliferation in response to environmental cues is critical for development and the maintenance of viability in all organisms. In unicellular organisms, such as the budding yeast Saccharomyces cerevisiae, growth and proliferation are regulated by nutrient availability. We have described changes in the pattern of protein synthesis during the growth of S. cerevisiae cells to stationary phase (E. K. Fuge, E. L. Braun, and M. Werner-Washburne, J. Bacteriol. 176:5802-5813, 1994) and noted a protein, which we designated Snz1p (p35), that shows increased synthesis after entry into stationary phase. We report here the identification of the SNZ1 gene, which encodes this protein. We detected increased SNZ1 mRNA accumulation almost 2 days after glucose exhaustion, significantly later than that of mRNAs encoded by other postexponential genes. SNZ1-related sequences were detected in phylogenetically diverse organisms by sequence comparisons and low-stringency hybridization. Multiple SNZ1-related sequences were detected in some organisms, including S. cerevisiae. Snz1p was found to be among the most evolutionarily conserved proteins currently identified, indicating that we have identified a novel, highly conserved protein involved in growth arrest in S. cerevisiae. The broad phylogenetic distribution, the regulation of the SNZ1 mRNA and protein in S. cerevisiae, and identification of a Snz protein modified during sporulation in the gram-positive bacterium Bacillus subtilis support the hypothesis that Snz proteins are part of an ancient response that occurs during nutrient limitation and growth arrest. PMID:8955308

  16. Functional Conservation of MIKC*-Type MADS Box Genes in Arabidopsis and Rice Pollen Maturation[C][W

    PubMed Central

    Liu, Yuan; Cui, Shaojie; Wu, Feng; Yan, Shuo; Lin, Xuelei; Du, Xiaoqiu; Chong, Kang; Schilling, Susanne; Theißen, Günter; Meng, Zheng

    2013-01-01

    There are two groups of MADS intervening keratin-like and C-terminal (MIKC)-type MADS box genes, MIKCC type and MIKC* type. In seed plants, the MIKCC type shows considerable diversity, but the MIKC* type has only two subgroups, P- and S-clade, which show conserved expression in the gametophyte. To examine the functional conservation of MIKC*-type genes, we characterized all three rice (Oryza sativa) MIKC*-type genes. All three genes are specifically expressed late in pollen development. The single knockdown or knockout lines, respectively, of the S-clade MADS62 and MADS63 did not show a mutant phenotype, but lines in which both S-clade genes were affected showed severe defects in pollen maturation and germination, as did knockdown lines of MADS68, the only P-clade gene in rice. The rice MIKC*-type proteins form strong heterodimeric complexes solely with partners from the other subclade; these complexes specifically bind to N10-type C-A-rich-G-boxes in vitro and regulate downstream gene expression by binding to N10-type promoter motifs. The rice MIKC* genes have a much lower degree of functional redundancy than the Arabidopsis thaliana MIKC* genes. Nevertheless, our data indicate that the function of heterodimeric MIKC*-type protein complexes in pollen development has been conserved since the divergence of monocots and eudicots, roughly 150 million years ago. PMID:23613199

  17. Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants, and humans.

    PubMed

    Hayashi, Kazuhiro; Ogiyama, Yuki; Yokomi, Kazumasa; Nakagawa, Tsuyoshi; Kaino, Tomohiro; Kawamukai, Makoto

    2014-01-01

    Coenzyme Q (CoQ) is an essential factor for aerobic growth and oxidative phosphorylation in the electron transport system. The biosynthetic pathway for CoQ has been proposed mainly from biochemical and genetic analyses of Escherichia coli and Saccharomyces cerevisiae; however, the biosynthetic pathway in higher eukaryotes has been explored in only a limited number of studies. We previously reported the roles of several genes involved in CoQ synthesis in the fission yeast Schizosaccharomyces pombe. Here, we expand these findings by identifying ten genes (dps1, dlp1, ppt1, and coq3-9) that are required for CoQ synthesis. CoQ10-deficient S. pombe coq deletion strains were generated and characterized. All mutant fission yeast strains were sensitive to oxidative stress, produced a large amount of sulfide, required an antioxidant to grow on minimal medium, and did not survive at the stationary phase. To compare the biosynthetic pathway of CoQ in fission yeast with that in higher eukaryotes, the ability of CoQ biosynthetic genes from humans and plants (Arabidopsis thaliana) to functionally complement the S. pombe coq deletion strains was determined. With the exception of COQ9, expression of all other human and plant COQ genes recovered CoQ10 production by the fission yeast coq deletion strains, although the addition of a mitochondrial targeting sequence was required for human COQ3 and COQ7, as well as A. thaliana COQ6. In summary, this study describes the functional conservation of CoQ biosynthetic genes between yeasts, humans, and plants.

  18. An evolutionarily conserved mutual interdependence between Aire and microRNAs in promiscuous gene expression.

    PubMed

    Ucar, Olga; Tykocinski, Lars-Oliver; Dooley, James; Liston, Adrian; Kyewski, Bruno

    2013-07-01

    The establishment and maintenance of central tolerance depends to a large extent on the ability of medullary thymic epithelial cells to express a variety of tissue-restricted antigens, the so-called promiscuous gene expression (pGE). Autoimmune regulator (Aire) is to date the best characterised transcriptional regulator known to at least partially coordinate pGE. There is accruing evidence that the expression of Aire-dependent and -independent genes is modulated by higher order chromatin configuration, epigenetic modifications and post-transcriptional control. Given the involvement of microRNAs (miRNAs) as potent post-transcriptional modulators of gene expression, we investigated their role in the regulation of pGE in purified mouse and human thymic epithelial cells (TECs). Microarray profiling of TEC subpopulations revealed evolutionarily conserved cell type and differentiation-specific miRNA signatures with a subset of miRNAs being significantly upregulated during terminal medullary thymic epithelial cell differentiation. The differential regulation of this subset of miRNAs was correlated with Aire expression and some of these miRNAs were misexpressed in the Aire knockout thymus. In turn, the specific absence of miRNAs in TECs resulted in a progressive reduction of Aire expression and pGE, affecting both Aire-dependent and -independent genes. In contrast, the absence of miR-29a only affected the Aire-dependent gene pool. These findings reveal a mutual interdependence of miRNA and Aire. © 2013 The Authors. European Journal of Immunology published byWiley-VCH Verlag GmbH & Co. KGaA Weinheim.

  19. IRES-dependent translated genes in fungi: computational prediction, phylogenetic conservation and functional association.

    PubMed

    Peguero-Sanchez, Esteban; Pardo-Lopez, Liliana; Merino, Enrique

    2015-12-15

    The initiation of translation via cellular internal ribosome entry sites plays an important role in the stress response and certain physiological conditions in which canonical cap-dependent translation initiation is compromised. Currently, only a limited number of these regulatory elements have been experimentally identified. Notably, cellular internal ribosome entry sites lack conservation of both the primary sequence and mRNA secondary structure, rendering their identification difficult. Despite their biological importance, the currently available computational strategies to predict them have had limited success. We developed a bioinformatic method based on a support vector machine for the prediction of internal ribosome entry sites in fungi using the 5'-UTR sequences of 20 non-redundant fungal organisms. Additionally, we performed a comparative analysis and characterization of the functional relationships among the gene products predicted to be translated by this cap-independent mechanism. Using our method, we predicted 6,532 internal ribosome entry sites in 20 non-redundant fungal organisms. Some orthologous groups were enriched with our positive predictions. This is the case of the HSP70 chaperone family, which remarkably has two verified internal ribosome entry sites, one in humans and the other in flies. A second example is the orthologous group of the eIF4G repression protein Sbp1p, which has two homologous genes known to be translated by this cap-independent mechanism, one in mice and the other in yeast. These examples emphasize the wide conservation of these regulatory elements as a result of selective pressure. In addition, we performed a protein-protein interaction network characterization of the gene products of our positive predictions using Saccharomyces cerevisiae as a model, which revealed a highly connected and modular topology, suggesting a functional association. A remarkable example of this functional association is our prediction of internal

  20. Deep Conservation of Genes Required for Both Drosophila melanogaster and Caenorhabditis elegans Sleep Includes a Role for Dopaminergic Signaling

    PubMed Central

    Singh, Komudi; Ju, Jennifer Y.; Walsh, Melissa B.; DiIorio, Michael A.; Hart, Anne C.

    2014-01-01

    Objectives: Cross-species conservation of sleep-like behaviors predicts the presence of conserved molecular mechanisms underlying sleep. However, limited experimental evidence of conservation exists. Here, this prediction is tested directly. Measurements and Results: During lethargus, Caenorhabditis elegans spontaneously sleep in short bouts that are interspersed with bouts of spontaneous locomotion. We identified 26 genes required for Drosophila melanogaster sleep. Twenty orthologous C. elegans genes were selected based on similarity. Their effect on C. elegans sleep and arousal during the last larval lethargus was assessed. The 20 most similar genes altered both the quantity of sleep and arousal thresholds. In 18 cases, the direction of change was concordant with Drosophila studies published previously. Additionally, we delineated a conserved genetic pathway by which dopamine regulates sleep and arousal. In C. elegans neurons, G-alpha S, adenylyl cyclase, and protein kinase A act downstream of D1 dopamine receptors to regulate these behaviors. Finally, a quantitative analysis of genes examined herein revealed that C. elegans arousal thresholds were directly correlated with amount of sleep during lethargus. However, bout duration varies little and was not correlated with arousal thresholds. Conclusions: The comprehensive analysis presented here suggests that conserved genes and pathways are required for sleep in invertebrates and, likely, across the entire animal kingdom. The genetic pathway delineated in this study implicates G-alpha S and previously known genes downstream of dopamine signaling in sleep. Quantitative analysis of various components of quiescence suggests that interdependent or identical cellular and molecular mechanisms are likely to regulate both arousal and sleep entry. Citation: Singh K, Ju JY, Walsh MB, Dilorio MA, Hart AC. Deep conservation of genes required for both Drosophila melanogaster and Caenorhabditis elegans sleep includes a role for

  1. Gene regulatory network plasticity predates a switch in function of a conserved transcription regulator

    PubMed Central

    Nocedal, Isabel; Mancera, Eugenio; Johnson, Alexander D

    2017-01-01

    The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number of connections needed to form a novel network arise over evolutionary time. Here, we address this question using the network controlled by the fungal transcription regulator Ndt80. This conserved protein has undergone a dramatic switch in function—from an ancestral role regulating sporulation to a derived role regulating biofilm formation. This switch in function corresponded to a large-scale rewiring of the genes regulated by Ndt80. However, we demonstrate that the Ndt80-target gene connections were undergoing extensive rewiring prior to the switch in Ndt80’s regulatory function. We propose that extensive drift in the Ndt80 regulon allowed for the exploration of alternative network structures without a loss of ancestral function, thereby facilitating the formation of a network with a new function. DOI: http://dx.doi.org/10.7554/eLife.23250.001 PMID:28327289

  2. Remarkable intron and exon sequence conservation in human and mouse homeobox Hox 1. 3 genes

    SciTech Connect

    Tournier-Lasserve, E.; Odenwald, W.F.; Garbern, J.; Trojanowski, J.; Lazzarini, R.A.

    1989-05-01

    A high degree of conservation exists between the Hox 1.3 homeobox genes of mice and humans. The two genes occupy the same relative positions in their respective Hox 1 gene clusters, they show extensive sequence similarities in their coding and noncoding portions, and both are transcribed into multiple transcripts of similar sizes. The predicted human Hox 1.3 protein differs from its murine counterpart in only 7 of 270 amino acids. The sequence similarity in the 250 base pairs upstream of the initiation codon is 98%, the similarity between the two introns, both 960 base pairs long, is 72%, and the similarity in the 3' noncoding region from termination codon to polyadenylation signal is 90%. Both mouse and human Hox 1.3 introns contain a sequence with homology to a mating-type-controlled cis element of the yeast Ty1 transposon. DNA-binding studies with a recombinant mouse Hox 1.3 protein identified two binding sites in the intron, both of which were within the region of shared homology with this Ty1 cis element.

  3. H3K36ac Is an Evolutionary Conserved Plant Histone Modification That Marks Active Genes.

    PubMed

    Mahrez, Walid; Arellano, Minerva Susana Trejo; Moreno-Romero, Jordi; Nakamura, Miyuki; Shu, Huan; Nanni, Paolo; Köhler, Claudia; Gruissem, Wilhelm; Hennig, Lars

    2016-03-01

    In eukaryotic cells, histones are subject to a large number of posttranslational modifications whose sequential or combinatorial action affects chromatin structure and genome function. We identified acetylation at Lys-36 in histone H3 (H3K36ac) as a new chromatin modification in plants. The H3K36ac modification is evolutionary conserved in seed plants, including the gymnosperm Norway spruce (Picea abies) and the angiosperms rice (Oryza sativa), tobacco (Nicotiana tabacum), and Arabidopsis (Arabidopsis thaliana). In Arabidopsis, H3K36ac is highly enriched in euchromatin but not in heterochromatin. Genome-wide chromatin immunoprecipitation sequencing experiments revealed that H3K36ac peaks at the 5' end of genes, mainly on the two nucleosomes immediately distal to the transcription start site, independently of gene length. H3K36ac overlaps with H3K4me3 and the H2A.Z histone variant. The histone acetyl transferase GCN5 and the histone deacetylase HDA19 are required for H3K36ac homeostasis. H3K36ac and H3K36me3 show negative crosstalk, which is mediated by GCN5 and the histone methyl transferase SDG8. Although H3K36ac is associated with gene activity, we did not find a linear relationship between H3K36ac and transcript levels, suggesting that H3K36ac is a binary indicator of transcription. © 2016 American Society of Plant Biologists. All Rights Reserved.

  4. Evolutionary analysis of two complement C4 genes: Ancient duplication and conservation during jawed vertebrate evolution.

    PubMed

    Nonaka, Mayumi I; Terado, Tokio; Kimura, Hiroshi; Nonaka, Masaru

    2017-03-01

    The complement C4 is a thioester-containing protein, and a histidine (H) residue catalyzes the cleavage of the thioester to allow covalent binding to carbohydrates on target cells. Some mammalian and teleost species possess an additional isotype where the catalytic H is replaced by an aspartic acid (D), which binds preferentially to proteins. We found the two C4 isotypes in many other jawed vertebrates, including sharks and birds/reptiles. Phylogenetic analysis suggested that C4 gene duplication occurred in the early days of the jawed vertebrate evolution. The D-type C4 of bony fish except for mammals formed a cluster, termed D-lineage. The D-lineage genes were located in a syntenic region outside MHC, and evolved conservatively. Mammals lost the D-lineage before speciation, but D-type C4 was regenerated by recent gene duplication in some mammalian species or groups. Dual C4 molecules with different substrate specificities would have contributed to development of the antibody-dependent classical pathway.

  5. Cloning and expression study of the lobster (Homarus americanus) vitellogenin: Conservation in gene structure among decapods.

    PubMed

    Tiu, Shirley Hiu Kwan; Hui, Ho-Lam; Tsukimura, Brian; Tobe, Stephen S; He, Jian-Guo; Chan, Siu-Ming

    2009-01-01

    This study reports the molecular characterization of the vitellogenin (Vg) of the lobster, Homarus americanus. Based on the annual collection of female lobsters, vitellogenesis commences in early March and continues through to September of each year. Using an antibody to vitellin of the lobster, H. americanus, several immunoreactive ovarian proteins were initially identified by Western blot analysis. The 80kDa protein contained the amino acid sequence APWGGNTPRC, identified subsequently by cDNA cloning to be identical to the lobster Vg. In common with the shrimp Metapenaeus ensis and crab Charybdis feriatus, the lobster HaVg1 gene comprises 14 introns and 15 exons. The deduced HaVg1 precursor is most similar to the Vg of the crayfish Cherax quadricarinatus (57%), followed by M. ensis (40-43% identity) and C. feriatus (38%). The results from genomic and RT-PCR cloning also confirmed the presence of multiple Vg genes in lobster. At early reproductive stages, the hepatopancreas HaVg1 transcript levels are low but increased to a maximum in animals with mature oocytes. The ovary, however, also expressed low levels of HaVg1. Using in vitro explant culture, treatment of hepatopancreas fragments with farnesoic acid or 20-hydroxyecdysone resulted in a significant stimulation in HaVg1 expression. From this study, it appears that Vg gene organization and expression pattern in decapods is highly conserved. Similar endocrine mechanisms may govern the process of vitellogenesis across the decapods.

  6. Identification, characterization and phylogenic analysis of conserved genes within the p74 gene region of Choristoneura fumiferana granulovirus genome.

    PubMed

    Rashidan, Kianoush Khajeh; Nassoury, Nasha; Giannopoulos, Paresa N; Mauffette, Yves; Guertin, Claude

    2004-11-30

    The genes located within the p74 gene region of the Choristoneura fumiferana granulovirus (ChfuGV) were identified by sequencing an 8.9 kb BamHI restriction fragment on the ChfuGV genome. The global guanine-cytosine (GC) content of this region of the genome was 33.02%. This paper presents the ORFs within the p74 gene region along with their transcriptional orientations. This region contains a total of 15 open reading frames (ORFs). Among those, 8 ORFs were found to be homologues to the baculoviral ORFs: Cf-i-p , Cf-vi, Cf-vii, Cf-viii (ubiquitin), Cf-xi (pp31), Cf-xii (lef-11), Cf-xiii (sod) and Cf-xv-p (p74). To date, no specific function has been assigned to the ORFs: Cf-i, Cf-ii, Cf-iii, Cf-iv, Cf-v, Cf-vi, Cf-vii, Cf-ix and Cf-x. The most noticeable ORFs located in this region of the ChfuGV genome were ubiquitin, lef-11, sod, fibrillin and p74. The phylogenetic trees (constructed using conceptual products of major conserved ORFs) and gene arrangement in this region were used to further examine the classification of the members of the granulovirus genus. Comparative studies demonstrated that ChfuGV along with the Cydia pomonella granulovirus (CpGV), Phthorimaea operculella granulovirus (PhopGV), Adoxophyes orana granulovirus (AoGV) and Cryptophlebia leucotreta granulovirus (ClGV) share a high degree of amino acids sequence and gene arrangement preservation within the studied region. These results support a previous report, which classified a granuloviruses into 2 distinct groups: Group I: ChfuGV, CpGV, PhopGV and AoGV and Group II: Xestia c-nigrum granulovirus (XcGV) and Plutella xylostella granulovirus (PxGV). The phylogenetic and gene arrangement studies also placed ClGV as a novel member of the Group I granuloviruses.

  7. Ultrasound demonstration of testicular microlithiasis in pediatric patients: is there an association with testicular germ cell tumors?

    PubMed

    Volokhina, Yulia V; Oyoyo, Udochukwu E; Miller, John H

    2014-01-01

    There is suggestion that testicular microlithiasis predicts risk of testicular malignancy, especially testicular germ cell tumors. This association remains uncertain. We retrospectively reviewed testicular germ cell tumor occurrence in patients with testicular microlithiasis to assess this association and determined the prevalence of testicular microlithiasis in symptomatic boys. This study was IRB and HIPAA compliant. Two-thousand six-hundred twenty-five testicular US exams performed on 2,266 children (younger than 19 years of age) in our institution from 2000 through 2011 were reviewed for presence of testicular microlithiasis and masses. Testicular microlithiasis was defined as presence of five or more testicular microcalcifications on a single US image. Incidence of testicular germ cell tumors was calculated in a group of patients with testicular microlithiasis and in a control group without testicular microlithiasis. Relative risk, odds ratio, 90% and 95%CI were calculated. Eighty-seven patients out of 2,266 had testicular microlithiasis. One child was found to have both testicular germ cell tumor and testicular microlithiasis. In 2,179 children without testicular microlithiasis, 8 had testicular germ cell tumors. Incidence of testicular microlithiasis was 3.8%. Incidence of testicular germ cell tumors in testicular microlithiasis patients was 1.2%, and 0.38% in non-testicular microlithiasis patients. Relative risk of testicular germ cell tumors in testicular microlithiasis patients vs. non-testicular microlithiasis patients was 3.13 (90%CI: 0.55-17.76; 95%CI: 0.40-24.76), odds ratio 3.16 (90%CI: 0.55-18.32; 95%CI: 0.39-25.5). There is no association between testicular microlithiasis and testicular germ cell tumors. We had hoped to do a meta-analysis, but only two studies had a sufficient case control group of non-testicular microlithiasis patients.

  8. Cloning of noggin gene from hydra and analysis of its functional conservation using Xenopus laevis embryos.

    PubMed

    Chandramore, Kalpana; Ito, Yuzuro; Takahashi, Shuji; Asashima, Makoto; Ghaskadbi, Surendra

    2010-01-01

    Hydra, a member of phylum Cnidaria that arose early in evolution, is endowed with a defined axis, organized nervous system, and active behavior. It is a powerful model system for the elucidation of evolution of developmental mechanisms in animals. Here, we describe the identification and cloning of noggin-like gene from hydra. Noggin is a secreted protein involved at multiple stages of vertebrate embryonic development including neural induction and is known to exert its effects by inhibiting the bone morphogenetic protein (BMP)-signaling pathway. Sequence analysis revealed that hydra Noggin shows considerable similarity with its orthologs at the amino acid level. When microinjected in the early Xenopus embryos, hydra noggin mRNA induced a secondary axis in 100% of the injected embryos, demonstrating functional conservation of hydra noggin in vertebrates. This was further confirmed by the partial rescue of Xenopus embryos by hydra noggin mRNA from UV-induced ventralization. By using animal cap assay in Xenopus embryos, we demonstrate that these effects of hydra noggin in Xenopus embryos are because of inhibition of BMP signaling by Noggin. Our data indicate that BMP/Noggin antagonism predates the bilaterian divergence and is conserved during the evolution.

  9. A case of testicular infarction from the complications of Klebsiella oxytoca induced acute epididymitis.

    PubMed

    Lee, Wonae; Park, Heeyoon; Lee, Gilho

    2016-04-01

    Herein, we reported a case of testicular infarction in a patient with Klebsiella oxytoca induced acute epididymitis. Acute left epididymitis progressed into testicular infarction requiring orchiectomy in spite of antibiotics treatment. Ordinary urine cultures did not reveal any specific organism, suggesting viable but noncultureable state. We amplified a bacterial 16S ribosomal subunit gene from the urine and orchiectomized samples, and we found K. oxytoca infections from both of them.

  10. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    NASA Astrophysics Data System (ADS)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  11. A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

    PubMed Central

    2010-01-01

    Background The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase) level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features. Results BAC shotgun sequencing of the hexaploid wheat (Triticum aestivum cv. Chinese Spring) genome has been used to assemble a group of 15 wheat BACs from the chromosome 3B physical map FPC contig ctg1034 into a 783,553 bp genomic sequence. This ctg1034 sequence was annotated for biological features such as genes and transposable elements. A three-gene island was identified among >80% repetitive DNA sequence. Using bioinformatics analysis there were no observable similarity in their gene functions. The ctg1034 gene island also displayed complete conservation of gene order and orientation with syntenic gene islands found in publicly available genome sequences of Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays, even though the intergenic space and introns were divergent. Conclusion We propose that ctg1034 is located within the heterochromatic C-band region of deletion bin 3BL7 based on the identification of heterochromatic tandem repeats and presence of significant matches to chromodomain-containing gypsy LTR retrotransposable elements. We also speculate that this location, among other highly repetitive sequences, may account for the relative stability in gene order and orientation within the gene

  12. Interspecific comparison of the period gene of Drosophila reveals large blocks of non-conserved coding DNA.

    PubMed Central

    Colot, H V; Hall, J C; Rosbash, M

    1988-01-01

    We have cloned and sequenced the coding region of the period (per) gene from Drosophila pseudoobscura and D. virilis. A comparison with that of D. melanogaster reveals that the conceptual translation products consist of interspersed blocks of conserved and non-conserved amino acid sequence. The non-conserved portion, comprising approximately 33% of the protein sequence, includes the perfect Thr-Gly repeat of D. melanogaster, which is absent from the D. pseudoobscura and D. virilis proteins. Based on these observations and cross-species transformation experiments, we suggest that the interspecific variability in the per primary amino acid sequence contributes to the control of species-specific behaviors. PMID:3208754

  13. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.

    PubMed

    Carmona-Antoñanzas, Greta; Tocher, Douglas R; Martinez-Rubio, Laura; Leaver, Michael J

    2014-01-15

    Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. © 2013.

  14. Members of the zinc finger protein gene family sharing a conserved N-terminal module.

    PubMed Central

    Rosati, M; Marino, M; Franzè, A; Tramontano, A; Grimaldi, G

    1991-01-01

    We report the isolation of human members of a sub-family of structurally related finger protein genes. These potentially encode polypeptides containing finger motifs of the Krüppel type at the C-terminus, and a conserved amino acid module at the N-terminus; because of its invariant location the latter is referred to as finger preceding box (FPB). The FPB, detected also in previously described finger proteins from human, mouse and Xenopus, extends over approximately 65 amino acids and appears to be composed of two contiguous modules: FPB-A (residues 1-42) and FPB-B (residues 43-65). The latter is absent in some of the members analyzed. Elements A and B and the zinc finger domain are encoded by separate exons in the ZNF2 gene, a human member of this sub-family. The positioning of introns within this gene is remarkable. One intron flanks and a second interrupts the first codon of the FPB-A and FPB-B modules, respectively. A third intron occurs a few nucleotides downstream of FPB-B marking its separation from the remainder of the coding sequences. This organization, together with the absence of FPB-B in some cDNAs, supports the hypothesis that mRNAs encoding polypeptides that include one, both or none of the FPB-A and FPB-B modules may be assembled through alternative splicing pathways. Northern analyses showed that members of this sub-family are expressed as multiple transcripts in several cell lines. The sequences of distinct cDNAs homologous to the ZNF2 gene indicate that alternative splicing events adjoin either coding or non coding exons to the FPB sequences. Images PMID:1945843

  15. Conserved but Attenuated Parental Gene Expression in Allopolyploids: Constitutive Zinc Hyperaccumulation in the Allotetraploid Arabidopsis kamchatica.

    PubMed

    Paape, Timothy; Hatakeyama, Masaomi; Shimizu-Inatsugi, Rie; Cereghetti, Teo; Onda, Yoshihiko; Kenta, Tanaka; Sese, Jun; Shimizu, Kentaro K

    2016-11-01

    Allopolyploidization combines parental genomes and often confers broader species distribution. However, little is known about parentally transmitted gene expression underlying quantitative traits following allopolyploidization because of the complexity of polyploid genomes. The allopolyploid species Arabidopsis kamchatica is a natural hybrid of the zinc hyperaccumulator Arabidopsis halleri and of the nonaccumulator Arabidopsis lyrata We found that A. kamchatica retained the ability to hyperaccumulate zinc from A. halleri and grows in soils with both low and high metal content. Hyperaccumulation of zinc by A. kamchatica was reduced to about half of A. halleri, but is 10-fold greater than A. lyrata Homeologs derived from A. halleri had significantly higher levels of expression of genes such as HEAVY METAL ATPASE4 (HMA4), METAL TRANSPORTER PROTEIN1 and other metal ion transporters than those derived from A. lyrata, which suggests cis-regulatory differences. A. kamchatica has on average about half the expression of these genes compared with A. halleri due to fixed heterozygosity inherent in allopolyploids. Zinc treatment significantly changed the ratios of expression of 1% of homeologous pairs, including genes putatively involved in metal homeostasis. Resequencing data showed a significant reduction in genetic diversity over a large genomic region (290 kb) surrounding the HMA4 locus derived from the A. halleri parent compared with the syntenic A. lyrata-derived region, which suggests different evolutionary histories. We also estimated that three A. halleri-derived HMA4 copies are present in A. kamchatica Our findings support a transcriptomic model in which environment-related transcriptional patterns of both parents are conserved but attenuated in the allopolyploids. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. Conserved but Attenuated Parental Gene Expression in Allopolyploids: Constitutive Zinc Hyperaccumulation in the Allotetraploid Arabidopsis kamchatica

    PubMed Central

    Paape, Timothy; Hatakeyama, Masaomi; Shimizu-Inatsugi, Rie; Cereghetti, Teo; Onda, Yoshihiko; Kenta, Tanaka; Sese, Jun; Shimizu, Kentaro K.

    2016-01-01

    Allopolyploidization combines parental genomes and often confers broader species distribution. However, little is known about parentally transmitted gene expression underlying quantitative traits following allopolyploidization because of the complexity of polyploid genomes. The allopolyploid species Arabidopsis kamchatica is a natural hybrid of the zinc hyperaccumulator Arabidopsis halleri and of the nonaccumulator Arabidopsis lyrata. We found that A. kamchatica retained the ability to hyperaccumulate zinc from A. halleri and grows in soils with both low and high metal content. Hyperaccumulation of zinc by A. kamchatica was reduced to about half of A. halleri, but is 10-fold greater than A. lyrata. Homeologs derived from A. halleri had significantly higher levels of expression of genes such as HEAVY METAL ATPASE4 (HMA4), METAL TRANSPORTER PROTEIN1 and other metal ion transporters than those derived from A. lyrata, which suggests cis-regulatory differences. A. kamchatica has on average about half the expression of these genes compared with A. halleri due to fixed heterozygosity inherent in allopolyploids. Zinc treatment significantly changed the ratios of expression of 1% of homeologous pairs, including genes putatively involved in metal homeostasis. Resequencing data showed a significant reduction in genetic diversity over a large genomic region (290 kb) surrounding the HMA4 locus derived from the A. halleri parent compared with the syntenic A. lyrata-derived region, which suggests different evolutionary histories. We also estimated that three A. halleri-derived HMA4 copies are present in A. kamchatica. Our findings support a transcriptomic model in which environment-related transcriptional patterns of both parents are conserved but attenuated in the allopolyploids. PMID:27413047

  17. Conservation of MAP kinase activity and MSP genes in parthenogenetic nematodes

    PubMed Central

    2010-01-01

    Background MAP (mitogen-activated protein) kinase activation is a prerequisite for oocyte maturation, ovulation and fertilisation in many animals. In the hermaphroditic nematode Caenorhabditis elegans, an MSP (major sperm protein) dependent pathway is utilised for MAP kinase activation and successive oocyte maturation with extracellular MSP released from sperm acting as activator. How oocyte-to-embryo transition is triggered in parthenogenetic nematode species that lack sperm, is not known. Results We investigated two key elements of oocyte-to-embryo transition, MSP expression and MAP kinase signaling, in two parthenogenetic nematodes and their close hermaphroditic relatives. While activated MAP kinase is present in all analysed nematodes irrespective of the reproductive mode, MSP expression differs. In contrast to hermaphroditic or bisexual species, we do not find MSP expression at the protein level in parthenogenetic nematodes. However, genomic sequence analysis indicates that functional MSP genes are present in several parthenogenetic species. Conclusions We present three alternative interpretations to explain our findings. (1) MSP has lost its function as a trigger of MAP kinase activation and is not expressed in parthenogenetic nematodes. Activation of the MAP kinase pathway is achieved by another, unknown mechanism. Functional MSP genes are required for occasionally emerging males found in some parthenogenetic species. (2) Because of long-term disadvantages, parthenogenesis is of recent origin. MSP genes remained intact during this short intervall although they are useless. As in the first scenario, an unknown mechanism is responsible for MAP kinase activation. (3) The molecular machinery regulating oocyte-to-embryo transition in parthenogenetic nematodes is conserved with respect to C. elegans, thus requiring intact MSP genes. However, MSP expression has been shifted to non-sperm cells and is reduced below the detection limits, but is still sufficient to

  18. Drugs Approved for Testicular Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  19. Testicular Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  20. Cancer testis antigen expression in testicular germ cell tumorigenesis.

    PubMed

    Bode, Peter K; Thielken, Andrea; Brandt, Simone; Barghorn, André; Lohe, Bernd; Knuth, Alexander; Moch, Holger

    2014-06-01

    Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in non-seminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas.

  1. Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice.

    PubMed

    Kwon, Jun Tae; Ham, Sera; Jeon, Suyeon; Kim, Youil; Oh, Seungmin; Cho, Chunghee

    2017-01-01

    The identification and characterization of germ cell-specific genes are essential if we hope to comprehensively understand the mechanisms of spermatogenesis and fertilization. Here, we searched the mouse UniGene databases and identified 13 novel genes as being putatively testis-specific or -predominant. Our in silico and in vitro analyses revealed that the expressions of these genes are testis- and germ cell-specific, and that they are regulated in a stage-specific manner during spermatogenesis. We generated antibodies against the proteins encoded by seven of the genes to facilitate their characterization in male germ cells. Immunoblotting and immunofluorescence analyses revealed that one of these proteins was expressed only in testicular germ cells, three were expressed in both testicular germ cells and testicular sperm, and the remaining three were expressed in sperm of the testicular stages and in mature sperm from the epididymis. Further analysis of the latter three proteins showed that they were all associated with cytoskeletal structures in the sperm flagellum. Among them, MORN5, which is predicted to contain three MORN motifs, is conserved between mouse and human sperm. In conclusion, we herein identify 13 authentic genes with male germ cell-specific expression, and provide comprehensive information about these genes and their encoded products. Our finding will facilitate future investigations into the functional roles of these novel genes in spermatogenesis and sperm functions.

  2. Sequence Similarity of Clostridium difficile Strains by Analysis of Conserved Genes and Genome Content Is Reflected by Their Ribotype Affiliation

    PubMed Central

    Kurka, Hedwig; Ehrenreich, Armin; Ludwig, Wolfgang; Monot, Marc; Rupnik, Maja; Barbut, Frederic; Indra, Alexander; Dupuy, Bruno; Liebl, Wolfgang

    2014-01-01

    PCR-ribotyping is a broadly used method for the classification of isolates of Clostridium difficile, an emerging intestinal pathogen, causing infections with increased disease severity and incidence in several European and North American countries. We have now carried out clustering analysis with selected genes of numerous C. difficile strains as well as gene content comparisons of their genomes in order to broaden our view of the relatedness of strains assigned to different ribotypes. We analyzed the genomic content of 48 C. difficile strains representing 21 different ribotypes. The calculation of distance matrix-based dendrograms using the neighbor joining method for 14 conserved genes (standard phylogenetic marker genes) from the genomes of the C. difficile strains demonstrated that the genes from strains with the same ribotype generally clustered together. Further, certain ribotypes always clustered together and formed ribotype groups, i.e. ribotypes 078, 033 and 126, as well as ribotypes 002 and 017, indicating their relatedness. Comparisons of the gene contents of the genomes of ribotypes that clustered according to the conserved gene analysis revealed that the number of common genes of the ribotypes belonging to each of these three ribotype groups were very similar for the 078/033/126 group (at most 69 specific genes between the different strains with the same ribotype) but less similar for the 002/017 group (86 genes difference). It appears that the ribotype is indicative not only of a specific pattern of the amplified 16S–23S rRNA intergenic spacer but also reflects specific differences in the nucleotide sequences of the conserved genes studied here. It can be anticipated that the sequence deviations of more genes of C. difficile strains are correlated with their PCR-ribotype. In conclusion, the results of this study corroborate and extend the concept of clonal C. difficile lineages, which correlate with ribotypes affiliation. PMID:24482682

  3. A WDR Gene Is a Conserved Member of a Chitin Synthase Gene Cluster and Influences the Cell Wall in Aspergillus nidulans

    PubMed Central

    Guerriero, Gea; Silvestrini, Lucia; Obersriebnig, Michael; Hausman, Jean-Francois; Strauss, Joseph; Ezcurra, Inés

    2016-01-01

    WD40 repeat (WDR) proteins are pleiotropic molecular hubs. We identify a WDR gene that is a conserved genomic neighbor of a chitin synthase gene in Ascomycetes. The WDR gene is unique to fungi and plants, and was called Fungal Plant WD (FPWD). FPWD is within a cell wall metabolism gene cluster in the Ascomycetes (Pezizomycotina) comprising chsD, a Chs activator and a GH17 glucanase. The FPWD, AN1556.2 locus was deleted in Aspergillus nidulans strain SAA.111 by gene replacement and only heterokaryon transformants were obtained. The re-annotation of Aspergilli genomes shows that AN1556.2 consists of two tightly linked separate genes, i.e., the WDR gene and a putative beta-flanking gene of unknown function. The WDR and the beta-flanking genes are conserved genomic neighbors localized within a recently identified metabolic cell wall gene cluster in genomes of Aspergilli. The heterokaryons displayed increased susceptibility to drugs affecting the cell wall, and their phenotypes, observed by optical, confocal, scanning electron and atomic force microscopy, suggest cell wall alterations. Quantitative real-time PCR shows altered expression of some cell wall-related genes. The possible implications on cell wall biosynthesis are discussed. PMID:27367684

  4. A WDR Gene Is a Conserved Member of a Chitin Synthase Gene Cluster and Influences the Cell Wall in Aspergillus nidulans.

    PubMed

    Guerriero, Gea; Silvestrini, Lucia; Obersriebnig, Michael; Hausman, Jean-Francois; Strauss, Joseph; Ezcurra, Inés

    2016-06-29

    WD40 repeat (WDR) proteins are pleiotropic molecular hubs. We identify a WDR gene that is a conserved genomic neighbor of a chitin synthase gene in Ascomycetes. The WDR gene is unique to fungi and plants, and was called Fungal Plant WD (FPWD). FPWD is within a cell wall metabolism gene cluster in the Ascomycetes (Pezizomycotina) comprising chsD, a Chs activator and a GH17 glucanase. The FPWD, AN1556.2 locus was deleted in Aspergillus nidulans strain SAA.111 by gene replacement and only heterokaryon transformants were obtained. The re-annotation of Aspergilli genomes shows that AN1556.2 consists of two tightly linked separate genes, i.e., the WDR gene and a putative beta-flanking gene of unknown function. The WDR and the beta-flanking genes are conserved genomic neighbors localized within a recently identified metabolic cell wall gene cluster in genomes of Aspergilli. The heterokaryons displayed increased susceptibility to drugs affecting the cell wall, and their phenotypes, observed by optical, confocal, scanning electron and atomic force microscopy, suggest cell wall alterations. Quantitative real-time PCR shows altered expression of some cell wall-related genes. The possible implications on cell wall biosynthesis are discussed.

  5. Conservation analysis predicts in vivo occupancy of glucocorticoid receptor-binding sequences at glucocorticoid-induced genes.

    PubMed

    So, Alex Yick-Lun; Cooper, Samantha B; Feldman, Brian J; Manuchehri, Mitra; Yamamoto, Keith R

    2008-04-15

    The glucocorticoid receptor (GR) interacts with specific GR-binding sequences (GBSs) at glucocorticoid response elements (GREs) to orchestrate transcriptional networks. Although the sequences of the GBSs are highly variable among different GREs, the precise sequence within an individual GRE is highly conserved. In this study, we examined whether sequence conservation of sites resembling GBSs is sufficient to predict GR occupancy of GREs at genes responsive to glucocorticoids. Indeed, we found that the level of conservation of these sites at genes up-regulated by glucocorticoids in mouse C3H10T1/2 mesenchymal stem-like cells correlated directly with the extent of occupancy by GR. In striking contrast, we failed to observe GR occupancy of GBSs at genes repressed by glucocorticoids, despite the occurrence of these sites at a frequency similar to that of the induced genes. Thus, GR occupancy of the GBS motif correlates with induction but not repression, and GBS conservation alone is sufficient to predict GR occupancy and GRE function at induced genes.

  6. Conservation, spillover and gene flow within a network of Northern European marine protected areas.

    PubMed

    Huserbråten, Mats Brockstedt Olsen; Moland, Even; Knutsen, Halvor; Olsen, Esben Moland; André, Carl; Stenseth, Nils Chr

    2013-01-01

    To ensure that marine protected areas (MPAs) benefit conservation and fisheries, the effectiveness of MPA designs has to be evaluated in field studies. Using an interdisciplinary approach, we empirically assessed the design of a network of northern MPAs where fishing for European lobster (Homarusgammarus) is prohibited. First, we demonstrate a high level of residency and survival (50%) for almost a year (363 days) within MPAs, despite small MPA sizes (0.5-1 km(2)). Second, we demonstrate limited export (4.7%) of lobsters tagged within MPAs (N = 1810) to neighbouring fished areas, over a median distance of 1.6 km out to maximum 21 km away from MPA centres. In comparison, median movement distance of lobsters recaptured within MPAs was 164 m, and recapture rate was high (40%). Third, we demonstrate a high level of gene flow within the study region, with an estimated F ST of less than 0.0001 over a ≈ 400 km coastline. Thus, the restricted movement of older life stages, combined with a high level of gene flow suggests that connectivity is primarily driven by larval drift. Larval export from the MPAs can most likely affect areas far beyond their borders. Our findings are of high importance for the design of MPA networks for sedentary species with pelagic early life stages.

  7. Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

    PubMed Central

    Marthandan, S.; Baumgart, M.; Priebe, S.; Groth, M.; Schaer, J.; Kaether, C.; Guthke, R.; Cellerino, A.; Platzer, M.; Diekmann, S.; Hemmerich, P.

    2016-01-01

    Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains. PMID:27140416

  8. The current source of human Alu retroposons is a conserved gene shared with Old World monkey

    SciTech Connect

    Britten, R.J.; Stout, D.B.; Davidson, E.H. )

    1989-05-01

    A significant fraction of human Alu repeated sequences are members of the precise, recently inserted class. A cloned member of this class has been used as a probe for interspecies hybridization and thermal stability determination. The probe was reassociated with human, mandrill, and spider monkey DNA under conditions such that only almost perfectly matching duplexes could form. Equally precise hybrids were formed with human and mandrill DNA (Old World monkey) but not with spider monkey DNA (New World). These measurements as well as reassociation kinetics show the presence in mandrill DNA of many precise class Alu sequences that are very similar or identical in quantity and sequence to those in human DNA. Human and mandrill are moderately distant species with a single-copy DNA divergence of about 6%. Nevertheless, their recently inserted Alu sequences arise by retroposition of transcripts of source genes with nearly identical sequences. Apparently a gene present in our common ancestor at the time of branching was inherited and highly conserved in sequence in both the lineage of Old World monkeys and the lineage of apes and man.

  9. Conserved and essential transcription factors for cellulase gene expression in ascomycete fungi

    PubMed Central

    Coradetti, Samuel T.; Craig, James P.; Xiong, Yi; Shock, Teresa; Tian, Chaoguang; Glass, N. Louise

    2012-01-01

    Rational engineering of filamentous fungi for improved cellulase production is hampered by our incomplete knowledge of transcriptional regulatory networks. We therefore used the model filamentous fungus Neurospora crassa to search for uncharacterized transcription factors associated with cellulose deconstruction. A screen of a N. crassa transcription factor deletion collection identified two uncharacterized zinc binuclear cluster transcription factors (clr-1 and clr-2) that were required for growth and enzymatic activity on cellulose, but were not required for growth or hemicellulase activity on xylan. Transcriptional profiling with next-generation sequencing methods refined our understanding of the N. crassa transcriptional response to cellulose and demonstrated that clr-1 and clr-2 were required for the bulk of that response, including induction of all major cellulase and some major hemicellulase genes. Functional CLR-1 was necessary for expression of clr-2 and efficient cellobiose utilization. Phylogenetic analyses showed that CLR-1 and CLR-2 are conserved in the genomes of most filamentous ascomycete fungi capable of degrading cellulose. In Aspergillus nidulans, a strain carrying a deletion of the clr-2 homolog (clrB) failed to induce cellulase gene expression and lacked cellulolytic activity on Avicel. Further manipulation of this control system in industrial production strains may significantly improve yields of cellulases for cellulosic biofuel production. PMID:22532664

  10. Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq.

    PubMed

    Marthandan, S; Baumgart, M; Priebe, S; Groth, M; Schaer, J; Kaether, C; Guthke, R; Cellerino, A; Platzer, M; Diekmann, S; Hemmerich, P

    2016-01-01

    Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.

  11. Conservation, Spillover and Gene Flow within a Network of Northern European Marine Protected Areas

    PubMed Central

    Huserbråten, Mats Brockstedt Olsen; Moland, Even; Knutsen, Halvor; Olsen, Esben Moland; André, Carl; Stenseth, Nils Chr.

    2013-01-01

    To ensure that marine protected areas (MPAs) benefit conservation and fisheries, the effectiveness of MPA designs has to be evaluated in field studies. Using an interdisciplinary approach, we empirically assessed the design of a network of northern MPAs where fishing for European lobster (Homarusgammarus) is prohibited. First, we demonstrate a high level of residency and survival (50%) for almost a year (363 days) within MPAs, despite small MPA sizes (0.5-1 km2). Second, we demonstrate limited export (4.7%) of lobsters tagged within MPAs (N = 1810) to neighbouring fished areas, over a median distance of 1.6 km out to maximum 21 km away from MPA centres. In comparison, median movement distance of lobsters recaptured within MPAs was 164 m, and recapture rate was high (40%). Third, we demonstrate a high level of gene flow within the study region, with an estimated FST of less than 0.0001 over a ≈ 400 km coastline. Thus, the restricted movement of older life stages, combined with a high level of gene flow suggests that connectivity is primarily driven by larval drift. Larval export from the MPAs can most likely affect areas far beyond their borders. Our findings are of high importance for the design of MPA networks for sedentary species with pelagic early life stages. PMID:24039927

  12. The pathogenic properties of a novel and conserved gene product, KerV, in proteobacteria.

    PubMed

    An, Dingding; Apidianakis, Yiorgos; Boechat, Ana Laura; Baldini, Regina L; Goumnerov, Boyan C; Rahme, Laurence G

    2009-09-25

    Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design.

  13. The Pathogenic Properties of a Novel and Conserved Gene Product, KerV, in Proteobacteria

    PubMed Central

    An, Dingding; Apidianakis, Yiorgos; Boechat, Ana Laura; Baldini, Regina L.; Goumnerov, Boyan C.; Rahme, Laurence G.

    2009-01-01

    Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design. PMID:19779606

  14. Cloning and characterization of murine Aqp5: evidence for a conserved aquaporin gene cluster.

    PubMed

    Krane, C M; Towne, J E; Menon, A G

    1999-05-01

    Aquaporin 5 (Aqp5), a member of the aquaporin family of membrane water channels, is thought to modulate the osmolality of fluids in the eye, lung, and salivary gland. Here, we report the cloning and genomic characterization of murine Aqp5 and its expression in relevant mouse tissues. This gene, comprised of four exons encoding 265 amino acids (121, 55, 28, and 61 amino acids respectively), is transcribed into an approximate 1.8-kb mRNA detected in lung, parotid, submandibular, sublingual, and lacrimal tissues. Aqp5 encodes a protein that is 98% identical to rat Aqp5. An Aqp5 antibody detects an approximately 27-kDa protein band in mouse lung, and an additional 29 kDa band in salivary gland. Cloning and physical mapping genomic fragments contiguous with Aqp5 revealed two other members of the aquaporin family: Aqp2 and Aqp6, arrayed head to tail in the order Aqp2-Aqp5-Aqp6, and provides evidence of a gene cluster conserved in order and orientation in both mice and humans.

  15. Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A.

    PubMed

    Drews, Valerie L; Shi, Kehui; de Haan, Georgius; Meisler, Miriam H

    2007-10-01

    SCN8A is a major neuronal sodium channel gene expressed throughout the central and peripheral nervous systems. Mutations of SCN8A result in movement disorders and impaired cognition. To investigate the basis for the tissue-specific expression of SCN8A, we located conserved, potentially regulatory sequences in the human, mouse, chicken, and fish genes by 5' RACE of brain RNA and genomic sequence comparison. A highly conserved 5' noncoding exon, exon 1c, is present in vertebrates from fish to mammals and appears to define the ancestral promoter region. The distance from exon 1c to the first coding exon increased tenfold during vertebrate evolution, largely by insertion of repetitive elements. The mammalian gene acquired three novel, mutually exclusive noncoding exons that are not represented in the lower vertebrates. Within the shared exon 1c, we identified four short sequence elements of 10-20 bp with an unusually high level of evolutionary conservation. The conserved elements are most similar to consensus sites for the transcription factors Pou6f1/Brn5, YY1, and REST/NRSF. Introduction of mutations into the predicted Pou6f1 and REST sites reduced promoter activity in transfected neuronal cells. A 470-bp promoter fragment containing all of the conserved elements directed brain-specific expression of the LacZ reporter in transgenic mice. Transgene expression was highest in hippocampal neurons and cerebellar Purkinje cells, consistent with the expression of the endogenous gene. The compact cluster of conserved regulatory elements in SCN8A provides a useful target for molecular analysis of neuronal gene expression.

  16. SOR1, a gene required for photosensitizer and singlet oxygen resistance in Cercospora fungi, is highly conserved in divergent organisms.

    PubMed

    Ehrenshaft, M; Jenns, A E; Chung, K R; Daub, M E

    1998-03-01

    Filamentous Cercospora fungi are resistant to photosensitizing compounds that generate singlet oxygen. C. nicotianae photosensitizer-sensitive mutants were restored to full resistance by transformation with SOR1 (Singlet Oxygen Resistance 1), a gene recovered from a wild-type genomic library. SOR1 null mutants generated via targeted gene replacement confirmed the requirement for SOR1 in photosensitizer resistance. SOR1 RNA is present throughout the growth cycle. Although resistance to singlet oxygen is rare in biological systems, SOR1, a gene with demonstrated activity against singlet-oxygen-generating photosensitizers, is highly conserved in organisms from widely diverse taxa. The characterization of SOR1 provides an additional phenotype to this large group of evolutionarily conserved genes.

  17. Conservation of the Exon-Intron Structure of Long Intergenic Non-Coding RNA Genes in Eutherian Mammals

    PubMed Central

    Chernikova, Diana; Managadze, David; Glazko, Galina V.; Makalowski, Wojciech; Rogozin, Igor B.

    2016-01-01

    The abundance of mammalian long intergenic non-coding RNA (lincRNA) genes is high, yet their functions remain largely unknown. One possible way to study this important question is to use large-scale comparisons of various characteristics of lincRNA with those of protein-coding genes for which a large body of functional information is available. A prominent feature of mammalian protein-coding genes is the high evolutionary conservation of the exon-intron structure. Comparative analysis of putative intron positions in lincRNA genes from various mammalian genomes suggests that some lincRNA introns have been conserved for over 100 million years, thus the primary and/or secondary structure of these molecules is likely to be functionally important. PMID:27429005

  18. The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation.

    PubMed

    Schumacher, A; Lichtarge, O; Schwartz, S; Magnuson, T

    1998-11-15

    Similar to Drosophila, murine Polycomb-group (PcG) genes regulate anterior-posterior patterning of segmented axial structures by transcriptional repression of homeotic gene expression. The murine PcG gene eed (embryonic ectoderm development) encodes a 441-amino-acid protein with five WD motifs which, except for the amino terminus, is highly homologous to Drosophila ESC (Extra Sex Combs). Here, sequence and expression analysis as well as chromosomal mapping of the human orthologue of eed is described. Absolute conservation of the human eed protein along with significant divergence at the nucleotide level reveals functional constraints operating on all residues. The human orthologue appears to be ubiquitously expressed and maps to chromsome 11q14.2-q22.3. Using the first WD motif of the beta-subunit of the bovine G protein as a structural reference, the predicted locations of two previously identified eed point mutations (A. Schumacher et al., 1996, Nature 383: 250-253) are also reported herein. The proline substitution (L196P) in the second WD motif of the l7Rn5(3354SB) null allele maps to the internal core of the inner end of the beta-propeller blade and is likely to disrupt protein folding. In contrast, the asparagine substitution (I193N) in the second WD motif of the hypomorphic l7Rn5(1989SB) allele maps onto the surface of the beta-propeller blade near the central cavity and may affect surface interactions without compromising propeller packing. These results illustrate the critical importance of all residues for eed function in mammals and support a model whereby the amino terminus might implement function(s) related to embryonic development in higher organisms. Copyright 1998 Academic Press.

  19. The importance of immune gene variability (MHC) in evolutionary ecology and conservation

    PubMed Central

    Sommer, Simone

    2005-01-01

    Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of

  20. Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene.

    PubMed

    Sheela Rani, C S; Soto-Pina, Alexandra; Iacovitti, Lorraine; Strong, Randy

    2013-07-01

    The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at -7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH-CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5'-TGACTAA at -7243 bp completely abolished the Dex-stimulated Luc activity of hTH-CRII construct. The AP-1 agonist, tetradeconoyl-12,13-phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP-1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid-responsive element in a 7 bp AP-1-like motif in the promoter region at -7.24 kb of the human TH gene.

  1. Conservation of the genes for dissimilatory sulfite reductase from Desulfovibrio vulgaris and Archaeoglobus fulgidus allows their detection by PCR.

    PubMed Central

    Karkhoff-Schweizer, R R; Huber, D P; Voordouw, G

    1995-01-01

    The structural genes for dissimilatory sulfite reductase (desulfoviridin) from Desulfovibrio vulgaris Hilden-borough were cloned as a 7.2-kbp SacII DNA fragment. Nucleotide sequencing indicated the presence of a third gene, encoding a protein of only 78 amino acids, immediately downstream from the genes for the alpha and beta subunits (dsvA and dsvB). We designated this protein DsvD and the gene encoding it the dsvD gene. The alpha- and beta-subunit sequences are highly homologous to those of the dissimilatory sulfite reductase from Archaeoglobus fulgidus, a thermophilic archaeal sulfate reducer, which grows optimally at 83 degrees C. A gene with significant homology to dsvD was also found immediately downstream from the dsrAB genes of A. fulgidus. The remarkable conservation of gene arrangement and sequence across domain (bacterial versus archaeal) and physical (mesophilic versus thermophilic) boundaries indicates an essential role for DsvD in dissimilatory sulfite reduction and allowed the construction of conserved deoxyoligonucleotide primers for detection of the dissimilatory sulfite reductase genes in the environment. PMID:7887608

  2. Structure and sequence conservation of hao cluster genes of autotrophic ammonia-oxidizing bacteria: evidence for their evolutionary history.

    PubMed

    Bergmann, David J; Hooper, Alan B; Klotz, Martin G

    2005-09-01

    Comparison of the organization and sequence of the hao (hydroxylamine oxidoreductase) gene clusters from the gammaproteobacterial autotrophic ammonia-oxidizing bacterium (aAOB) Nitrosococcus oceani and the betaproteobacterial aAOB Nitrosospira multiformis and Nitrosomonas europaea revealed a highly conserved gene cluster encoding the following proteins: hao, hydroxylamine oxidoreductase; orf2, a putative protein; cycA, cytochrome c(554); and cycB, cytochrome c(m)(552). The deduced protein sequences of HAO, c(554), and c(m)(552) were highly similar in all aAOB despite their differences in species evolution and codon usage. Phylogenetic inference revealed a broad family of multi-c-heme proteins, including HAO, the pentaheme nitrite reductase, and tetrathionate reductase. The c-hemes of this group also have a nearly identical geometry of heme orientation, which has remained conserved during divergent evolution of function. High sequence similarity is also seen within a protein family, including cytochromes c(m)(552), NrfH/B, and NapC/NirT. It is proposed that the hydroxylamine oxidation pathway evolved from a nitrite reduction pathway involved in anaerobic respiration (denitrification) during the radiation of the Proteobacteria. Conservation of the hydroxylamine oxidation module was maintained by functional pressure, and the module expanded into two separate narrow taxa after a lateral gene transfer event between gamma- and betaproteobacterial ancestors of extant aAOB. HAO-encoding genes were also found in six non-aAOB, either singly or tandemly arranged with an orf2 gene, whereas a c(554) gene was lacking. The conservation of the hao gene cluster in general and the uniqueness of the c(554) gene in particular make it a suitable target for the design of primers and probes useful for molecular ecology approaches to detect aAOB.

  3. The expression pattern of genes involved in early neurogenesis suggests distinct and conserved functions in the diplopod Glomeris marginata.

    PubMed

    Pioro, Hilary L; Stollewerk, Angelika

    2006-01-01

    We have shown recently that the expression and function of proneural genes is conserved in chelicerates and myriapods, although groups of neural precursors are specified in the ventral neuroectoderm of these arthropod groups, rather than single cells as in insects and crustaceans. We present additional evidence that the pattern of neurogenesis seen in chelicerates and in previously analyzed myriapod species is representative of both arthropod groups, by analysing the formation of neural precursors in the diplopod Archispirostreptus sp. This raises the question as to what extent the genetic network has been modified to result in different modes of neurogenesis in the arthropod group. To find out which components of the neural genetic network might account for the different mode of neural precursor formation in chelicerates and myriapods, we identified genes in the diplopod Glomeris marginata that are known to be involved in early neurogenesis in Drosophila and studied their expression pattern. In Drosophila, early neurogenesis is controlled by proneural genes that encode HLH transcription factors. These genes belong to two major subfamilies, the achaete-scute group and the atonal group. Different proneural proteins activate both a common neural programme and distinct neuronal subtype-specific target genes. We show that the expression pattern of homologs of the Drosophila proneural genes daughterless, atonal, and Sox B1 are partially conserved in Glomeris mariginata. While the expression of the pan-neural gene snail is conserved in the ventral neuroectoderm of G. marginata, we found an additional expression domain in the ventral midline. We conclude that, although the components of the genetic network involved in specification of neural precursors seem to be conserved in chelicerates, myriapods, and Drosophila, the function of some of the genes might have changed during evolution.

  4. Conserved pattern of antisense overlapping transcription in the homologous human ERCC-1 and yeast RAD10 DNA repair gene regions.

    PubMed Central

    van Duin, M; van Den Tol, J; Hoeijmakers, J H; Bootsma, D; Rupp, I P; Reynolds, P; Prakash, L; Prakash, S

    1989-01-01

    We report that the genes for the homologous Saccharomyces cerevisiae RAD10 and human ERCC-1 DNA excision repair proteins harbor overlapping antisense transcription units in their 3' regions. Since naturally occurring antisense transcription is rare in S. cerevisiae and humans (this is the first example in human cells), our findings indicate that antisense transcription in the ERCC-1-RAD10 gene regions represents an evolutionarily conserved feature. Images PMID:2471070

  5. Structure and Sequence Conservation of hao Cluster Genes of Autotrophic Ammonia-Oxidizing Bacteria: Evidence for Their Evolutionary History

    PubMed Central

    Bergmann, David J.; Hooper, Alan B.; Klotz, Martin G.

    2005-01-01

    Comparison of the organization and sequence of the hao (hydroxylamine oxidoreductase) gene clusters from the gammaproteobacterial autotrophic ammonia-oxidizing bacterium (aAOB) Nitrosococcus oceani and the betaproteobacterial aAOB Nitrosospira multiformis and Nitrosomonas europaea revealed a highly conserved gene cluster encoding the following proteins: hao, hydroxylamine oxidoreductase; orf2, a putative protein; cycA, cytochrome c554; and cycB, cytochrome cm552. The deduced protein sequences of HAO, c554, and cm552 were highly similar in all aAOB despite their differences in species evolution and codon usage. Phylogenetic inference revealed a broad family of multi-c-heme proteins, including HAO, the pentaheme nitrite reductase, and tetrathionate reductase. The c-hemes of this group also have a nearly identical geometry of heme orientation, which has remained conserved during divergent evolution of function. High sequence similarity is also seen within a protein family, including cytochromes cm552, NrfH/B, and NapC/NirT. It is proposed that the hydroxylamine oxidation pathway evolved from a nitrite reduction pathway involved in anaerobic respiration (denitrification) during the radiation of the Proteobacteria. Conservation of the hydroxylamine oxidation module was maintained by functional pressure, and the module expanded into two separate narrow taxa after a lateral gene transfer event between gamma- and betaproteobacterial ancestors of extant aAOB. HAO-encoding genes were also found in six non-aAOB, either singly or tandemly arranged with an orf2 gene, whereas a c554 gene was lacking. The conservation of the hao gene cluster in general and the uniqueness of the c554 gene in particular make it a suitable target for the design of primers and probes useful for molecular ecology approaches to detect aAOB. PMID:16151127

  6. A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity.

    PubMed

    Li, Qingyun; Barish, Scott; Okuwa, Sumie; Maciejewski, Abigail; Brandt, Alicia T; Reinhold, Dominik; Jones, Corbin D; Volkan, Pelin Cayirlioglu

    2016-01-01

    Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.

  7. A conserved role for CUP-SHAPED COTYLEDON genes during ovule development.

    PubMed

    Gonçalves, Beatriz; Hasson, Alice; Belcram, Katia; Cortizo, Millán; Morin, Halima; Nikovics, Krisztina; Vialette-Guiraud, Aurélie; Takeda, Seiji; Aida, Mitsuhiro; Laufs, Patrick; Arnaud, Nicolas

    2015-08-01

    The evolution of plant reproductive strategies has led to a remarkable diversity of structures, especially within the flower, a structure characteristic of the angiosperms. In flowering plants, sexual reproduction depends notably on the development of the gynoecium that produces and protects the ovules. In Arabidopsis thaliana, ovule initiation is promoted by the concerted action of auxin with CUC1 (CUP-SHAPED COTYLEDON1) and CUC2, two genes that encode transcription factors of the NAC family (NAM/ATAF1,2/CUC). Here we highlight an additional role for CUC2 and CUC3 in Arabidopsis thaliana ovule separation. While CUC1 and CUC2 are broadly expressed in the medial tissue of the gynoecium, CUC2 and CUC3 are expressed in the placental tissue between developing ovules. Consistent with the partial overlap between CUC1, CUC2 and CUC3 expression patterns, we show that CUC proteins can physically interact, both in yeast cells and in planta. We found that the cuc2;cuc3 double mutant specifically harbours defects in ovule separation, producing fused seeds that share the seed coat, and suggesting that CUC2 and CUC3 promote ovule separation in a partially redundant manner. Functional analyses show that CUC transcription factors are also involved in ovule development in Cardamine hirsuta. Additionally we show a conserved expression pattern of CUC orthologues between ovule primordia in other phylogenetically distant species with different gynoecium architectures. Taken together these results suggest an ancient role for CUC transcription factors in ovule separation, and shed light on the conservation of mechanisms involved in the development of innovative structures. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  8. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation.

    PubMed

    Wang, Jianbo; Hamblet, Natasha S; Mark, Sharayne; Dickinson, Mary E; Brinkman, Brendan C; Segil, Neil; Fraser, Scott E; Chen, Ping; Wallingford, John B; Wynshaw-Boris, Anthony

    2006-05-01

    The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension.

  9. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation

    PubMed Central

    Wang, Jianbo; Hamblet, Natasha S.; Mark, Sharayne; Dickinson, Mary E.; Brinkman, Brendan C.; Segil, Neil; Fraser, Scott E.; Chen, Ping; Wallingford, John B.; Wynshaw-Boris, Anthony

    2014-01-01

    The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension. PMID:16571627

  10. A conserved splicing mechanism of the LMNA gene controls premature aging.

    PubMed

    Lopez-Mejia, Isabel C; Vautrot, Valentin; De Toledo, Marion; Behm-Ansmant, Isabelle; Bourgeois, Cyril F; Navarro, Claire L; Osorio, Fernando G; Freije, José M P; Stévenin, James; De Sandre-Giovannoli, Annachiara; Lopez-Otin, Carlos; Lévy, Nicolas; Branlant, Christiane; Tazi, Jamal

    2011-12-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and leads to the production of a truncated protein (progerin) with a dominant negative effect. Here we show that HGPS mutation changes the accessibility of the 5'SS of LMNA exon 11 which is sequestered in a conserved RNA structure. Our results also reveal a regulatory role of a subset of serine-arginine (SR)-rich proteins, including serine-arginine rich splicing factor 1 (SRSF1) and SRSF6, on utilization of the 5'SS leading to lamin A or progerin production and a modulation of this regulation in the presence of the c.1824C>T mutation is shown directly on HGPS patient cells. Mutant mice carrying the equivalent mutation in the LMNA gene (c.1827C>T) also accumulate progerin and phenocopy the main cellular alterations and clinical defects of HGPS patients. RNAi-induced depletion of SRSF1 in the HGPS-like mouse embryonic fibroblasts (MEFs) allowed progerin reduction and dysmorphic nuclei phenotype correction, whereas SRSF6 depletion aggravated the HGPS-like MEF's phenotype. We demonstrate that changes in the splicing ratio between lamin A and progerin are key factors for lifespan since heterozygous mice harboring the mutation lived longer than homozygous littermates but less than the wild-type. Genetic and biochemical data together favor the view that physiological progerin production is under tight control of a conserved splicing mechanism to avoid precocious aging.

  11. A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity

    PubMed Central

    Okuwa, Sumie; Maciejewski, Abigail; Brandt, Alicia T.; Reinhold, Dominik; Jones, Corbin D.; Volkan, Pelin Cayirlioglu

    2016-01-01

    Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1–4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity. PMID:26765103

  12. Two males with SRY-positive 46,XX testicular disorder of sex development.

    PubMed

    Gunes, Sezgin; Asci, Ramazan; Okten, Gülsen; Atac, Fatih; Onat, Onur E; Ogur, Gonul; Aydin, Oguz; Ozcelik, Tayfun; Bagci, Hasan

    2013-02-01

    The 46,XX testicular disorder of sex development (46,XX testicular DSD) is a rare phenotype associated with disorder of the sex chromosomes. We describe the clinical, molecular, and cytogenetic findings of a 16- and a 30-year-old male patient with sex-determining region Y (SRY)-positive 46,XX testicular DSD. Chromosomal analysis revealed 46,XX karyotype. Fluorescence in situ hybridization (FISH) showed the SRY region translocated to the short arm of the X chromosome. The presence of the SRY gene was also confirmed by polymerase chain reaction (PCR). The X chromosome inactivation (XCI) assay showed that both patients have a random pattern of X chromosome inactivation. This report compares the symptoms and features of the SRY-positive 46,XX testicular DSD patients.

  13. Comparative genomics of the Hlx homeobox gene and protein: conservation of structure and expression from fish to mammals.

    PubMed

    Bates, Michael D; Wells, James M; Venkatesh, Byrappa

    2005-06-06

    Hlx is a homeobox transcription factor gene that is expressed in intestinal and hepatic mesenchyme of the developing mouse embryo and is essential for normal intestinal and hepatic development. Because of the morphological and molecular similarities in the development of the digestive system across species, we hypothesized that the Hlx gene and protein sequences and expression patterns would be conserved among vertebrates. Comparison of the Hlx gene orthologues of human, chimpanzee, mouse, rat, pufferfish (Fugu) and zebrafish demonstrates that these six genes share an identical organization with four exons and three introns. Comparison of the inferred Hlx protein sequences from these and three additional species (chick, Spanish ribbed newt and rainbow trout) reveals significant sequence identity, with identical homeodomains. The expression of Hlx in the mesenchyme of developing chick embryos is highly similar to that of mouse. Fugu Hlx is expressed in a tissue-specific manner that is similar though not identical to that of mouse, suggesting a conservation of Hlx function between mammals and birds. The mammalian and fish Hlx genes share a putative 5' upstream enhancer as well as an inverted repeat containing CCAAT boxes on opposite strands that we have previously shown to be important for mouse Hlx gene expression. These results suggest that the function of Hlx and the mechanisms regulating its expression are highly conserved in mammals, birds, amphibians and fish.

  14. The narrow sheath duplicate genes: sectors of dual aneuploidy reveal ancestrally conserved gene functions during maize leaf development.

    PubMed Central

    Scanlon, M J; Chen, K D; McKnight CC, I V

    2000-01-01

    The narrow sheath mutant of maize displays a leaf and plant stature phenotype controlled by the duplicate factor mutations narrow sheath1 and narrow sheath2. Mutant leaves fail to develop a lateral domain that includes the leaf margins. Genetic data are presented to show that the narrow sheath mutations map to duplicated chromosomal regions, reflecting an ancestral duplication of the maize genome. Genetic and cytogenetic evidence indicates that the original mutation at narrow sheath2 is associated with a chromosomal inversion on the long arm of chromosome 4. Meristematic sectors of dual aneuploidy were generated, producing plants genetically mosaic for NARROW SHEATH function. These mosaic plants exhibited characteristic half-plant phenotypes, in which leaves from one side of the plant were of nonmutant morphology and leaves from the opposite side were of narrow sheath mutant phenotype. The data suggest that the narrow sheath duplicate genes may perform ancestrally conserved, redundant functions in the development of a lateral domain in the maize leaf. PMID:10880496

  15. Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

    PubMed Central

    Wang, Yonggang; Xin, Ying; Tan, Yi

    2017-01-01

    Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT) and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2. PMID:28191275

  16. The role of tree improvement programs for ex situ gene conservation of coastal Douglas-fir in the Pacific Northwest.

    Treesearch

    Sara R. Lipow; G. Randy Johnson; J. Bradley St. Claiff; Keith J. Jayawickrama

    2003-01-01

    We enumerate the genetic resources for coastal Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) in tree improvement programs in the Pacific Northwest USA and evaluate how they contribute to gene conservation of the species. The first-generation programs include over four million progeny from 33,928 selections...

  17. An evolutionarily conserved gene, FUWA, plays a role in determining panicle architecture, grain shape and grain weight in rice.

    PubMed

    Chen, Jun; Gao, He; Zheng, Xiao-Ming; Jin, Mingna; Weng, Jian-Feng; Ma, Jin; Ren, Yulong; Zhou, Kunneng; Wang, Qi; Wang, Jie; Wang, Jiu-Lin; Zhang, Xin; Cheng, Zhijun; Wu, Chuanyin; Wang, Haiyang; Wan, Jian-Min

    2015-08-01

    Plant breeding relies on creation of novel allelic combinations for desired traits. Identification and utilization of beneficial alleles, rare alleles and evolutionarily conserved genes in the germplasm (referred to as 'hidden' genes) provide an effective approach to achieve this goal. Here we show that a chemically induced null mutation in an evolutionarily conserved gene, FUWA, alters multiple important agronomic traits in rice, including panicle architecture, grain shape and grain weight. FUWA encodes an NHL domain-containing protein, with preferential expression in the root meristem, shoot apical meristem and inflorescences, where it restricts excessive cell division. Sequence analysis revealed that FUWA has undergone a bottleneck effect, and become fixed in landraces and modern cultivars during domestication and breeding. We further confirm a highly conserved role of FUWA homologs in determining panicle architecture and grain development in rice, maize and sorghum through genetic transformation. Strikingly, knockdown of the FUWA transcription level by RNA interference results in an erect panicle and increased grain size in both indica and japonica genetic backgrounds. This study illustrates an approach to create new germplasm with improved agronomic traits for crop breeding by tapping into evolutionary conserved genes. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  18. Conservation of major surface protein 1 genes of Anaplasma marginale during cyclic transmission between ticks and cattle.

    PubMed

    Bowie, Michael V; de la Fuente, Jose; Kocan, Katherine M; Blouin, Edmour F; Barbet, Anthony F

    2002-01-09

    Bovine anaplasmosis is a rickettsial disease of world-wide economic importance caused by Anaplasma marginale. Several major surface proteins with conserved gene sequences have been examined as potential candidates for vaccines and/or diagnostic assays. Major surface protein 1 (MSP1) is composed of polypeptides MSP1a and MSP1b. MSP1a is expressed from the single copy gene msp1 alpha and MSP1b is expressed by members of the msp1 beta multigene family. In order to determine if the msp1 genes are conserved, primers specific for msp1 alpha, msp1 beta(1), and msp1 beta(2) genes were synthesized and used to amplify msp1 sequences of A. marginale from tick cell cultures, from cattle during acute and chronic infections and from salivary glands of Dermacentor variabilis. Protein sequences of MSP1a, MSP1b(1) and MSP1b(2) were conserved during the life cycle of the parasite. No amino acid changes were observed in MSP1a. However, small variations were observed in the MSP1b(1) and MSP1b(2) protein sequences, which could be attributed to recombination, selection for sub-populations of A. marginale in the vertebrate host and/or PCR errors. Several isolate-specific sequences were also observed. Based on the information obtained in this study, the MSP1 protein appears to be fairly well conserved and a potential vaccine candidate.

  19. THE GRK4 SUBFAMILY OF G PROTEIN-COUPLED RECEPTOR KINASES: ALTERNATIVE SPLICING, GENE ORGANIZATION, AND SEQUENCE CONSERVATION

    EPA Science Inventory

    The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation.

    Premont RT, Macrae AD, Aparicio SA, Kendall HE, Welch JE, Lefkowitz RJ.

    Department of Medicine, Howard Hughes Medical Institute, Duke Univer...

  20. THE GRK4 SUBFAMILY OF G PROTEIN-COUPLED RECEPTOR KINASES: ALTERNATIVE SPLICING, GENE ORGANIZATION, AND SEQUENCE CONSERVATION

    EPA Science Inventory

    The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation.

    Premont RT, Macrae AD, Aparicio SA, Kendall HE, Welch JE, Lefkowitz RJ.

    Department of Medicine, Howard Hughes Medical Institute, Duke Univer...

  1. The Bacterial iprA Gene Is Conserved across Enterobacteriaceae, Is Involved in Oxidative Stress Resistance, and Influences Gene Expression in Salmonella enterica Serovar Typhimurium

    PubMed Central

    Herman, Allison; Serfecz, Jacquelyn; Kinnally, Alexandra; Crosby, Kathleen; Youngman, Matthew; Wykoff, Dennis

    2016-01-01

    ABSTRACT The iprA gene (formerly known as yaiV or STM0374) is located in a two-gene operon in the Salmonella enterica serovar Typhimurium genome and is associated with altered expression during spaceflight and rotating-wall-vessel culture conditions that increase virulence. However, iprA is uncharacterized in the literature. In this report, we present the first targeted characterization of this gene, which revealed that iprA is highly conserved across Enterobacteriaceae. We found that S. Typhimurium, Escherichia coli, and Enterobacter cloacae ΔiprA mutant strains display a multi-log-fold increase in oxidative stress resistance that is complemented using a plasmid-borne wild-type (WT) copy of the S. Typhimurium iprA gene. This observation was also associated with increased catalase activity, increased S. Typhimurium survival in macrophages, and partial dependence on the katE gene and full dependence on the rpoS gene. Our results indicate that IprA protein activity is sensitive to deletion of the N- and C-terminal 10 amino acids, while a region that includes amino acids 56 to 80 is dispensable for activity. RNA sequencing (RNA-Seq) analysis revealed several genes altered in expression in the S. Typhimurium ΔiprA mutant strain compared to the WT, including those involved in fimbria formation, spvABCD-mediated virulence, ethanolamine utilization, the phosphotransferase system (PTS) transport, and flagellin phase switching from FlgB to FliC (likely a stochastic event) and several genes of hypothetical or putative function. IMPORTANCE Overall, this work reveals that the conserved iprA gene measurably influences bacterial biology and highlights the pool of currently uncharacterized genes that are conserved across bacterial genomes. These genes represent potentially useful targets for bacterial engineering, vaccine design, and other possible applications. PMID:27246569

  2. Conservation of Gene Order and Content in the Circular Chromosomes of ‘Candidatus Liberibacter asiaticus’ and Other Rhizobiales

    PubMed Central

    Kuykendall, L. David; Shao, Jonathan Y.; Hartung, John S.

    2012-01-01

    ‘Ca. Liberibacter asiaticus,’ an insect-vectored, obligate intracellular bacterium associated with citrus-greening disease, also called “HLB," is a member of the Rhizobiales along with nitrogen-fixing microsymbionts Sinorhizobium meliloti and Bradyrhizobium japonicum, plant pathogen Agrobacterium tumefaciens and facultative intracellular mammalian pathogen Bartonella henselae. Comparative analyses of their circular chromosomes identified 514 orthologous genes shared among all five species. Shared among all five species are 50 identical blocks of microsyntenous orthologous genes (MOGs), containing a total of 283 genes. While retaining highly conserved genomic blocks of microsynteny, divergent evolution, horizontal gene transfer and niche specialization have disrupted macrosynteny among the five circular chromosomes compared. Highly conserved microsyntenous gene clusters help define the Rhizobiales, an order previously defined by 16S RNA gene similarity and herein represented by the three families: Bartonellaceae, Bradyrhizobiaceae and Rhizobiaceae. Genes without orthologs in the other four species help define individual species. The circular chromosomes of each of the five Rhizobiales species examined had genes lacking orthologs in the other four species. For example, 63 proteins are encoded by genes of ‘Ca. Liberibacter asiaticus’ not shared with other members of the Rhizobiales. Of these 63 proteins, 17 have predicted functions related to DNA replication or RNA transcription, and some of these may have roles related to low genomic GC content. An additional 17 proteins have predicted functions relevant to cellular processes, particularly modifications of the cell surface. Seventeen unshared proteins have specific metabolic functions including a pathway to synthesize cholesterol encoded by a seven-gene operon. The remaining 12 proteins encoded by ‘Ca. Liberibacter asiaticus’ genes not shared with other Rhizobiales are of bacteriophage origin.

  3. Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora.

    PubMed

    Cornelis, Guillaume; Heidmann, Odile; Bernard-Stoecklin, Sibylle; Reynaud, Karine; Véron, Géraldine; Mulot, Baptiste; Dupressoir, Anne; Heidmann, Thierry

    2012-02-14

    Syncytins are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires--primates, rodents, and lagomorphs--shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest syncytin gene identified to date, and it is the first in a new major clade of eutherian mammals.

  4. What Are the Key Statistics about Testicular Cancer?

    MedlinePlus

    ... Cancer About Testicular Cancer What Are the Key Statistics About Testicular Cancer? The American Cancer Society’s estimates ... you would like to know more about survival statistics, see Testicular cancer survival rates . Visit the American ...

  5. Comparative analysis of a conserved zinc finger gene cluster on human chromosome 19q and mouse chromosome 7.

    PubMed

    Shannon, M; Ashworth, L K; Mucenski, M L; Lamerdin, J E; Branscomb, E; Stubbs, L

    1996-04-01

    Several lines of evidence now suggest that many of the zinc-finger-containing (ZNF) genes in the human genome are arranged in clusters. However, little is known about the structure or function of the clusters or about their conservation throughout evolution. Here, we report the analysis of a conserved ZNF gene cluster located in human chromosome 19q13.2 and mouse chromosome 7. Our results indicate that the human cluster consists of at least 10 related Kruppel-associated box (KRAB)-containing ZNF genes organized in tandem over a distance of 350-450 kb. Two cDNA clones representing genes in the murine cluster have been studied in detail. The KRAB A domains of these genes are nearly identical and are highly similar to human 19q13.2-derived KRAB sequences, but DNA-binding ZNF domains and other portions of the genes differ considerably. The two murine genes display distinct expression patterns, but are coexpressed in some adult tissues. These studies pave the way for a systematic analysis of the evolution of structure and function of genes within the numerous clustered ZNF families located on human chromosome 19 and elsewhere in the human and mouse genomes.

  6. Patterns of Evolutionary Conservation of Ascorbic Acid-Related Genes Following Whole-Genome Triplication in Brassica rapa

    PubMed Central

    Duan, Weike; Song, Xiaoming; Liu, Tongkun; Huang, Zhinan; Ren, Jun; Hou, Xilin; Du, Jianchang; Li, Ying

    2015-01-01

    Ascorbic acid (AsA) is an important antioxidant in plants and an essential vitamin for humans. Extending the study of AsA-related genes from Arabidopsis thaliana to Brassica rapa could shed light on the evolution of AsA in plants and inform crop breeding. In this study, we conducted whole-genome annotation, molecular-evolution and gene-expression analyses of all known AsA-related genes in B. rapa. The nucleobase–ascorbate transporter (NAT) gene family and AsA l-galactose pathway genes were also compared among plant species. Four important insights gained are that: 1) 102 AsA-related gene were identified in B. rapa and they mainly diverged 12–18 Ma accompanied by the Brassica-specific genome triplication event; 2) during their evolution, these AsA-related genes were preferentially retained, consistent with the gene dosage hypothesis; 3) the putative proteins were highly conserved, but their expression patterns varied; and 4) although the number of AsA-related genes is higher in B. rapa than in A. thaliana, the AsA contents and the numbers of expressed genes in leaves of both species are similar, the genes that are not generally expressed may serve as substitutes during emergencies. In summary, this study provides genome-wide insights into evolutionary history and mechanisms of AsA-related genes following whole-genome triplication in B. rapa. PMID:25552535

  7. Patterns of evolutionary conservation of ascorbic acid-related genes following whole-genome triplication in Brassica rapa.

    PubMed

    Duan, Weike; Song, Xiaoming; Liu, Tongkun; Huang, Zhinan; Ren, Jun; Hou, Xilin; Du, Jianchang; Li, Ying

    2014-12-31

    Ascorbic acid (AsA) is an important antioxidant in plants and an essential vitamin for humans. Extending the study of AsA-related genes from Arabidopsis thaliana to Brassica rapa could shed light on the evolution of AsA in plants and inform crop breeding. In this study, we conducted whole-genome annotation, molecular-evolution and gene-expression analyses of all known AsA-related genes in B. rapa. The nucleobase-ascorbate transporter (NAT) gene family and AsA l-galactose pathway genes were also compared among plant species. Four important insights gained are that: 1) 102 AsA-related gene were identified in B. rapa and they mainly diverged 12-18 Ma accompanied by the Brassica-specific genome triplication event; 2) during their evolution, these AsA-related genes were preferentially retained, consistent with the gene dosage hypothesis; 3) the putative proteins were highly conserved, but their expression patterns varied; and 4) although the number of AsA-related genes is higher in B. rapa than in A. thaliana, the AsA contents and the numbers of expressed genes in leaves of both species are similar, the genes that are not generally expressed may serve as substitutes during emergencies. In summary, this study provides genome-wide insights into evolutionary history and mechanisms of AsA-related genes following whole-genome triplication in B. rapa.

  8. Male-enhanced expression and genetic conservation of a gene isolated with an anti-H-Y antibody.

    PubMed

    Lau, Y F; Chan, K M; Kan, Y W; Goldberg, E

    1987-01-01

    The hypothesis of the serological H-Y antigen as the inducer molecule for mammalian male sex differentiation has been considered an important working model in developmental biology. However, because of the difficulties involved in its detection, supporting evidence in molecular terms is lacking for this hypothesis. The isolation of the gene for the serological H-Y antigen is essential to the acertainment of its proposed functions. Using recombinant DNA technology and specific anti-H-Y sera we have isolated a candidate gene, the MEA gene, for the serological H-Y antigen. Molecular characterization of the MEA gene shows male-enhanced expression and genetic conservation patterns similar to those attributed to the serological H-Y antigen. The isolation of this candidate gene for the serological H-Y antigen. The isolation of this candidate gene for the serological H-Y antigen would allow further investigations to identify the functions for this molecule in molecular terms.

  9. Expression of a mutant androgen receptor in cloned fibroblasts derived from a heterozygous carrier for the syndrome of testicular feminization.

    PubMed Central

    Elawady, M K; Allman, D R; Griffin, J E; Wilson, J D

    1983-01-01

    Thermolability of androgen binding was compared in fibroblasts cloned from normal female skin, skin from a subject with testicular feminization whose mutation is known to be associated with a thermolabile androgen receptor, and from the mother of the subject with testicular feminization. Seven of 28 clones studied from the mother exhibited thermolability of binding, indicating that the mutant gene that causes thermolability of binding, like the gene responsible for the normal androgen receptor, is X-linked. PMID:6602545

  10. Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals.

    PubMed

    Park, Seung Gu; Hannenhalli, Sridhar; Choi, Sun Shim

    2014-06-26

    Genomes of higher eukaryotes have surprisingly long first introns and in some cases, the first introns have been shown to have higher conservation relative to other introns. However, the functional relevance of conserved regions in the first introns is poorly understood. Leveraging the recent ENCODE data, here we assess potential regulatory roles of conserved regions in the first intron of human genes. We first show that relative to other downstream introns, the first introns are enriched for blocks of highly conserved sequences. We also found that the first introns are enriched for several chromatin marks indicative of active regulatory regions and this enrichment of regulatory marks is correlated with enrichment of conserved blocks in the first intron; the enrichments of conservation and regulatory marks in first intron are not entirely explained by a general, albeit variable, bias for certain marks toward the 5' end of introns. Interestingly, conservation as well as proportions of active regulatory chromatin marks in the first intron of a gene correlates positively with the numbers of exons in the gene but the correlation is significantly weakened in second introns and negligible beyond the second intron. The first intron conservation is also positively correlated with the gene's expression level in several human tissues. Finally, a gene-wise analysis shows significant enrichments of active chromatin marks in conserved regions of first introns, relative to the conserved regions in other introns of the same gene. Taken together, our analyses strongly suggest that first introns are enriched for active transcriptional regulatory signals under purifying selection.

  11. Comparative Analysis of Pistil Transcriptomes Reveals Conserved and Novel Genes Expressed in Dry, Wet, and Semidry Stigmas1[W

    PubMed Central

    Allen, Alexandra M.; Lexer, Christian; Hiscock, Simon J.

    2010-01-01

    Fertilization in angiosperms depends on a complex cellular “courtship” between haploid pollen and diploid pistil. These pollen-pistil interactions are regulated by a diversity of molecules, many of which remain to be identified and characterized. Thus, it is unclear to what extent these processes are conserved among angiosperms, a fact confounded by limited sampling across taxa. Here, we report the analysis of pistil-expressed genes in Senecio squalidus (Asteraceae), a species from euasterid II, a major clade for which there are currently no data on pistil-expressed genes. Species from the Asteraceae characteristically have a “semidry stigma,” intermediate between the “wet” and “dry” stigmas typical of the majority of angiosperms. Construction of pistil-enriched cDNA libraries for S. squalidus allowed us to address two hypotheses: (1) stigmas of S. squalidus will express genes common to wet and dry stigmas and genes specific to the semidry stigma characteristic of the Asteraceae; and (2) genes potentially essential for pistil function will be conserved between diverse angiosperm groups and therefore common to all currently available pistil transcriptome data sets, including S. squalidus. Our data support both these hypotheses. The S. squalidus pistil transcriptome contains novel genes and genes previously identified in pistils of species with dry stigmas and wet stigmas. Comparative analysis of the five pistil transcriptomes currently available (Oryza sativa, Crocus sativus, Arabidopsis thaliana, Nicotiana tabacum, and S. squalidus), representing four major angiosperm clades and the three stigma states, identified novel genes and conserved genes potentially regulating pollen-pistil interaction pathways common to monocots and eudicots. PMID:20813907

  12. A set of genes conserved in sequence and expression traces back the establishment of multicellularity in social amoebae.

    PubMed

    Schilde, Christina; Lawal, Hajara M; Noegel, Angelika A; Eichinger, Ludwig; Schaap, Pauline; Glöckner, Gernot

    2016-11-04

    The developmental cycle of Dictyostelid amoebae represents an early form of multicellularity with cell type differentiation. Mutant studies in the model Dictyostelium discoideum revealed that its developmental program integrates the actions of genes involved in signal transduction, adhesion, motility, autophagy and cell wall and matrix biosynthesis. However, due to functional redundancy and fail safe options not required in the laboratory, this single organism approach cannot capture all essential genes. To understand how multicellular organisms evolved, it is essential to recognize both the conserved core features of their developmental programs and the gene modifications that instigated phenotypic innovation. For complex organisms, such as animals, this is not within easy reach, but it is feasible for less complex forms, such as the Dictyostelid social amoebas. We compared global profiles of gene expression during the development of four social amoebae species that represent 600 mya of Dictyostelia evolution, and identified orthologous conserved genes with similar developmental up-regulation of expression using three different methods. For validation, we disrupted five genes of this core set and examined the phenotypic consequences. At least 71 of the developmentally regulated genes that were identified with all methods were likely to be already present in the last ancestor of all Dictyostelia. The lack of phenotypic changes in null mutants indicates that even highly conserved genes either participate in functionally redundant pathways or are necessary for developmental progression under adverse, non-standard laboratory conditions. Both mechanisms provide robustness to the developmental program, but impose a limit on the information that can be obtained from deleting single genes.

  13. Candidate genes associated with testicular development, sperm quality, and hormone levels of inhibin, luteinizing hormone, and insulin-like growth factor 1 in Brahman bulls.

    PubMed

    Fortes, Marina R S; Reverter, Antonio; Hawken, Rachel J; Bolormaa, Sunduimijid; Lehnert, Sigrid A

    2012-09-01

    Bull fertility is an important target for genetic improvement, and early prediction using genetic markers is therefore a goal for livestock breeding. We performed genome-wide association studies to identify genes associated with fertility traits measured in young bulls. Data from 1118 Brahman bulls were collected for six traits: blood hormone levels of inhibin (IN) at 4 mo, luteinizing hormone (LH) following a gonadotropin-releasing hormone challenge at 4 mo, and insulin-like growth factor 1 (IGF1) at 6 mo, scrotal circumference (SC) at 12 mo, ability to produce sperm (Sperm) at 18 mo, and percentage of normal sperm (PNS) at 24 mo. All the bulls were genotyped with the BovineSNP50 chip. Sires and dams of the bull population (n = 304) were genotyped with the high-density chip (∼800 000 polymorphisms) to allow for imputation, thereby contributing detail on genome regions of interest. Polymorphism associations were discovered for all traits, except for Sperm. Chromosome 2 harbored polymorphisms associated with IN. For LH, associated polymorphisms were located in five different chromosomes. A region of chromosome 14 contained polymorphisms associated with IGF1 and SC. Regions of the X chromosome showed associations with SC and PNS. Associated polymorphisms yielded candidate genes in chromosomes 2, 14, and X. These findings will contribute to the development of genetic markers to help select cattle with improved fertility and will lead to better annotation of gene function in the context of reproductive biology.

  14. Timely diagnosis of testicular cancer.

    PubMed

    Moul, Judd W

    2007-05-01

    Early detection of testicular tumors has been touted as beneficial for more than 100 years. In earlier eras, early detection was virtually the only way to improve outcomes. According to statistics that have been tracked in the literature, however, the delay from initial symptoms to definitive diagnosis by radical orchiectomy has averaged 4 to 5 months. In the modern era of effective chemotherapy, the effects of a delayed diagnosis on survival can be overcome but at the cost of a more morbid treatment regimen. Although screening on a population basis is not currently recommended by the National Cancer Institute, teaching testicular self examination to young men, particularly those who have risk factors, is reasonable.

  15. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

    PubMed

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  16. Variable Gene Dispersal Conditions and Spatial Deforestation Patterns Can Interact to Affect Tropical Tree Conservation Outcomes

    PubMed Central

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H.

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with ‘Near’ distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  17. Testicular growth and development in puberty.

    PubMed

    Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

    2017-06-01

    To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

  18. Maximal Expression of the Evolutionarily Conserved Slit2 Gene Promoter Requires Sp1

    PubMed Central

    Saunders, Jacquelyn; Wisidagama, D. Roonalika; Morford, Travis; Malone, Cindy S.

    2015-01-01

    Slit2 is a neural axon guidance and chemorepellent protein that stimulates motility in a variety of cell types. The role of Slit2 in neural development and neoplastic growth and migration has been well established, while the genetic mechanisms underlying regulation of the Slit2 gene have not. We identified the core and proximal promoter of Slit2 by mapping multiple transcriptional start sites, analyzing transcriptional activity, and confirming sequence homology for the Slit2 proximal promoter among a number of species. Deletion series and transient transfection identified the Slit2 proximal promoter as within 399 base pairs upstream of the start of transcription. A crucial region for full expression of the Slit2 proximal promoter lies between 399 base pairs and 296 base pairs upstream of the start of transcription. Computer modeling identified three transcription factor binding consensus sites within this region, of which only site-directed mutagenesis of one of the two identified Sp1 consensus sites inhibited transcriptional activity of the Slit2 proximal promoter (−399 to +253). Bioinformatics analysis of the Slit2 proximal promoter −399 base pair to −296 base pair region shows high sequence conservation over twenty-two species, and that this region follows an expected pattern of sequence divergence through evolution. PMID:26456684

  19. blue cheese Mutations Define a Novel, Conserved Gene Involved in Progressive Neural Degeneration

    PubMed Central

    Finley, Kim D.; Edeen, Philip T.; Cumming, Robert C.; Mardahl-Dumesnil, Michelle D.; Taylor, Barbara J.; Rodriguez, Maria H.; Hwang, Calvin E.; Benedetti, Michael; McKeown, Michael

    2007-01-01

    A common feature of many human neurodegenerative diseases is the accumulation of insoluble ubiquitin-containing protein aggregates in the CNS. Although Drosophila has been helpful in understanding several human neurodegenerative disorders, a loss-of-function mutation has not been identified that leads to insoluble CNS protein aggregates. The study of Drosophila mutations may identify unique components that are associated with human degenerative diseases. The Drosophila blue cheese (bchs) gene defines such a novel degenerative pathway. bchs mutants have a reduced adult life span with the age-dependent formation of protein aggregates throughout the neuropil of the CNS. These inclusions contain insoluble ubiquitinated proteins and amyloid precursor-like protein. Progressive loss of CNS size and morphology along with extensive neuronal apoptosis occurs in aged bchs mutants. BCHS protein is widely expressed in the cytoplasm of CNS neurons and is present over the entire length of axonal projections. BCHS is nearly 3500 amino acids in size, with the last 1000 amino acids consisting of three functional protein motifs implicated in vesicle transport and protein processing. This region along with previously unidentified proteins encoded in the human, mouse, and nematode genomes shows striking homology along the full length of the BCHS protein. The high degree of conservation between Drosophila and human bchs suggests that study of the functional pathway of BCHS and associated mutant phenotype may provide useful insights into human neurodegenerative disorders. PMID:12598614

  20. Refining the regulatory region upstream of SOX9 associated with 46,XX testicular disorders of Sex Development (DSD).

    PubMed

    Hyon, Capucine; Chantot-Bastaraud, Sandra; Harbuz, Radu; Bhouri, Rakia; Perrot, Nicolas; Peycelon, Matthieu; Sibony, Mathilde; Rojo, Sandra; Piguel, Xavier; Bilan, Frederic; Gilbert-Dussardier, Brigitte; Kitzis, Alain; McElreavey, Ken; Siffroi, Jean-Pierre; Bashamboo, Anu

    2015-08-01

    Disorders of Sex Development (DSD) are a heterogeneous group of disorders affecting gonad and/or genito-urinary tract development and usually the endocrine-reproductive system. A genetic diagnosis is made in only around 20% of these cases. The genetic causes of 46,XX-SRY negative testicular DSD as well as ovotesticular DSD are poorly defined. Duplications involving a region located ∼600 kb upstream of SOX9, a key gene in testis development, were reported in several cases of 46,XX DSD. Recent studies have narrowed this region down to a 78 kb interval that is duplicated or deleted respectively in 46,XX or 46,XY DSD. We identified three phenotypically normal patients presenting with azoospermia and 46,XX testicular DSD. Two brothers carried a 83.8 kb duplication located ∼600 kb upstream of SOX9 that overlapped with the previously reported rearrangements. This duplication refines the minimal region associated with 46,XX-SRY negative DSD to a 40.7-41.9 kb element located ∼600 kb upstream of SOX9. Predicted enhancer elements and evolutionary-conserved binding sites for proteins known to be involved in testis determination are located within this region.

  1. Evidence for positive selection of taurine genes within a QTL region on chromosome X associated with testicular size in Australian Brahman cattle

    PubMed Central

    2014-01-01

    Background Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69–77 and 81–92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped. Results To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential. Conclusions Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation. PMID:24410912

  2. Evidence for positive selection of taurine genes within a QTL region on chromosome X associated with testicular size in Australian Brahman cattle.

    PubMed

    Lyons, Russell E; Loan, Nguyen To; Dierens, Leanne; Fortes, Marina R S; Kelly, Matthew; McWilliam, Sean S; Li, Yutao; Bunch, Rowan J; Harrison, Blair E; Barendse, William; Lehnert, Sigrid A; Moore, Stephen S

    2014-01-10

    Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69-77 and 81-92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped. To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential. Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation.

  3. A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts

    PubMed Central

    de la Calle-Mustienes, Elisa; Feijóo, Cármen Gloria; Manzanares, Miguel; Tena, Juan J.; Rodríguez-Seguel, Elisa; Letizia, Annalisa; Allende, Miguel L.; Gómez-Skarmeta, José Luis

    2005-01-01

    Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression. PMID:16024824

  4. Conserved 5' flank homologies in dipteran 5S RNA genes that would function on 'A' form DNA.

    PubMed Central

    Rubacha, A; Sumner, W; Richter, L; Beckingham, K

    1984-01-01

    We have sequenced the 480 base pair (bp) repeating unit of the 5S RNA genes of the Dipteran fly Calliphora erythrocephala and compared this sequence to the three known 5S RNA gene sequences from the Dipteran Genus Drosophila (1,2). A striking series of five perfectly conserved homologies identically positioned within the 5' flanks of all four Dipteran 5S RNA coding regions has thus been identified. The spacing (12-13 bp) between all of these homologies is typical of A form rather than B form DNA. Given that the eukaryotic 5S RNA gene specific initiation factor TFIIIA (3) is a DNA unwinding protein (4), a role for these Dipteran 5' flank homologies in initiation site selection on 5S RNA genes transiently unwound for transcription is suggested. One of the Dipteran homology blocks is highly conserved in sequence and position in all but one of the eukaryotic 5S RNA gene sequences known to date (17/18 genes). Its sequence (consensus: TATAAG) and position (average center: -26 bp) are highly reminiscent of the polymerase II gene 'TATA' box (5). PMID:6209610

  5. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    PubMed

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others.

  6. FK506, a calcineurin inhibitor, prevents cadmium-induced testicular toxicity in mice.

    PubMed

    Martin, Lisa Joy; Chen, Haiyan; Liao, Xiaoyan; Allayee, Hooman; Shih, Diana Mouhan; Lee, Grace Sangeun; Hovland, David Norman; Robbins, Wendie Anne; Carnes, Kay; Hess, Rex Allen; Lusis, Aldons Jake; Collins, Michael David

    2007-12-01

    Cadmium, a ubiquitous environmental contaminant, damages several major organs in humans and other mammals. The molecular mechanisms for damage are not known. At high doses (5 mg/kg cadmium chloride or higher), testicular damage in mice, rats, and other rodents includes interstitial edema, hemorrhage, and changes in the seminiferous tubules affecting spermatogenesis. Necrosis is evident by 48 h. The goal of this study was to fine map and identify the cdm gene, a gene that when mutated prevents cadmium-induced testicular toxicity in mouse strains with a mutation in this gene. A serine-threonine phosphatase, calcineurin (CN), subunit A, alpha isoform (Ppp3ca), was one of the seven candidates in the cdm region that was narrowed from 5.6 to 2.0 Mb on mouse chromosome 3. An inhibitor of CN, the immunosuppressant, FK506, prevented cadmium-induced testicular damage in five pathological categories, including vascular endothelial and seminiferous epithelial endpoints. Inductively coupled plasma-mass spectrometry revealed that FK506 protected without lowering the amount of cadmium in the testes. Ppp3ca(-/-) mice were investigated but were found to exhibit endogenous testicular abnormalities, making them an inappropriate model for determining whether the inactivation of the Ppp3ca gene would afford protection from cadmium-induced testicular toxicity. The protection afforded by FK506, found by the current study, indicated that CN is likely to be important in the mechanism of cadmium toxicity in the testis and possibly other organs.

  7. Testicular shielding in penile brachytherapy

    PubMed Central

    Bindal, Arpita; Tambe, Chandrashekhar M.; Ghadi, Yogesh; Murthy, Vedang; Shrivastava, Shyam Kishore

    2015-01-01

    Purpose Penile cancer, although rare, is one of the common genitourinary cancers in India affecting mostly aged uncircumcised males. For patients presenting with small superficial lesions < 3 cm restricted to glans, surgery, radical external radiation or brachytherapy may be offered, the latter being preferred as it allows organ and function preservation. In patients receiving brachytherapy, testicular morbidity is not commonly addressed. With an aim to minimize and document the doses to testis after adequate shielding during radical interstitial brachytherapy for penile cancers, we undertook this study in 2 patients undergoing brachytherapy and forms the basis of this report. Material and methods Two patients with early stage penile cancer limited to the glans were treated with radical high-dose-rate (HDR) brachytherapy using interstitial implant. A total of 7-8 tubes were implanted in two planes, parallel to the penile shaft. A total dose of 44-48 Gy (55-60 Gy EQD2 doses with α/β = 10) was delivered in 11-12 fractions of 4 Gy each delivered twice daily. Lead sheets adding to 11 mm (4-5 half value layer) were interposed between the penile shaft and scrotum. The testicular dose was measured using thermoluminescent dosimeters. For each patient, dosimetry was done for 3 fractions and mean calculated. Results The cumulative testicular dose to left and right testis was 31.68 cGy and 42.79 cGy for patient A, and 21.96 cGy and 23.28 cGy for patient B. For the same patients, the mean cumulative dose measured at the posterior aspect of penile shaft was 722.15 cGy and 807.72 cGy, amounting to 16.4% and 16.8% of the prescribed dose. Hence, the application of lead shield 11 mm thick reduced testicular dose from 722-808 cGy to 21.96-42.57 cGy, an “absolute reduction” of 95.99 ± 1.5%. Conclusions With the use of a simple lead shield as described, we were able to effectively reduce testicular dose from “spermicidal” range to “oligospermic” range with possible

  8. Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats

    PubMed Central

    Kopalli, Spandana Rajendra; Cha, Kyu-Min; Jeong, Min-Sik; Lee, Sang-Ho; Sung, Jong-Hwan; Seo, Seok-Kyo; Kim, Si-Kwan

    2015-01-01

    Background To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods Hydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results GINST treatment (50 μg/mL, 100 μg/mL, and 200 μg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 μM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 μg/mL and 100 μg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-α, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility. PMID:27158240

  9. Conservation and loss of ribosomal RNA gene sites in diploid and polyploid Fragaria (Rosaceae)

    PubMed Central

    2011-01-01

    Background The genus Fragaria comprises species at ploidy levels ranging from diploid (2n = 2x = 14) to decaploid (2n = 10x = 70). Fluorescence in situ hybridization with 5S and 25S rDNA probes was performed to gather cytogenetic information that illuminates genomic divergence among different taxa at multiple ploidy levels, as well as to explore the evolution of ribosomal RNA genes during polyploidization in Fragaria. Results Root tip cells of diploid taxa were typified by two 5S and six 25S rDNA hybridization signals of varying intensities, providing a baseline for comparisons within the genus. In three exceptional diploid genotypes, F. nilgerrensis (CFRA 1358 and CFRA 1825) and F. vesca 'Yellow Wonder', two 5S but only four 25S rDNA sites were found but with differing site losses. The numbers of 5S and 25S rDNA signals, respectively were three and nine in a triploid F. ×bifera accession, and were four and twelve in three tetraploids, thus occurring in proportional 1.5× and 2× multiples of the typical diploid pattern. In hexaploid F. moschata, a proportional multiple of six 5S rDNA sites was observed, but the number of 25S rDNA sites was one or two less than the proportionate prediction of eighteen. This apparent tendency toward rDNA site loss at higher ploidy was markedly expanded in octoploids, which displayed only two 5S and ten 25S rDNA sites. In the two decaploids examined, the numbers of 5S and 25S rDNA signals, respectively, were four and fifteen in F. virginiana subsp. platypetala, and six and twelve in F. iturupensis. Conclusions Among diploid Fragaria species, a general consistency of rDNA site numbers implies conserved genomic organization, but highly variable 25S signal sizes and intensities and two instances of site loss suggest concurrent high dynamics of rDNA copy numbers among both homologs and non-homologs. General conservation of rDNA site numbers in lower ploidy, but marked site number reductions at higher ploidy levels, suggest complex

  10. Mitochondrial genomes of Clymenella torquata (Maldanidae) and Riftia pachyptila (Siboglinidae): evidence for conserved gene order in annelida.

    PubMed

    Jennings, Robert M; Halanych, Kenneth M

    2005-02-01

    Mitochondrial genomes are useful tools for inferring evolutionary history. However, many taxa are poorly represented by available data. Thus, to further understand the phylogenetic potential of complete mitochondrial genome sequence data in Annelida (segmented worms), we examined the complete mitochondrial sequence for Clymenella torquata (Maldanidae) and an estimated 80% of the sequence of Riftia pachyptila (Siboglinidae). These genomes have remarkably similar gene orders to previously published annelid genomes, suggesting that gene order is conserved across annelids. This result is interesting, given the high variation seen in the closely related Mollusca and Brachiopoda. Phylogenetic analyses of DNA sequence, amino acid sequence, and gene order all support the recent hypothesis that Sipuncula and Annelida are closely related. Our findings suggest that gene order data is of limited utility in annelids but that sequence data holds promise. Additionally, these genomes show AT bias (approximately 66%) and codon usage biases but have a typical gene complement for bilaterian mitochondrial genomes.

  11. Conservation and Expression Patterns Divergence of Ascorbic Acid d-mannose/l-galactose Pathway Genes in Brassica rapa

    PubMed Central

    Duan, Weike; Ren, Jun; Li, Yan; Liu, Tongkun; Song, Xiaoming; Chen, Zhongwen; Huang, Zhinan; Hou, Xilin; Li, Ying

    2016-01-01

    Ascorbic acid (AsA) participates in diverse biological processes, is regulated by multiple factors and is a potent antioxidant and cellular reductant. The D-Mannose/L-Galactose pathway is a major plant AsA biosynthetic pathway that is highly connected within biosynthetic networks, and generally conserved across plants. Previous work has shown that, although most genes of this pathway are expressed under standard growth conditions in Brassica rapa, some paralogs of these genes are not. We hypothesize that regulatory evolution in duplicate AsA pathway genes has occurred as an adaptation to environmental stressors, and that gene retention has been influenced by polyploidation events in Brassicas. To test these hypotheses, we explored the conservation of these genes in Brassicas and their expression patterns divergence in B. rapa. Similar retention and a high degree of gene sequence similarity were identified in B. rapa (A genome), B. oleracea (C genome) and B. napus (AC genome). However, the number of genes that encode the same type of enzymes varied among the three plant species. With the exception of GMP, which has nine genes, there were one to four genes that encoded the other enzymes. Moreover, we found that expression patterns divergence widely exists among these genes. (i) VTC2 and VTC5 are paralogous genes, but only VTC5 is influenced by FLC. (ii) Under light treatment, PMI1 co-regulates the AsA pool size with other D-Man/L-Gal pathway genes, whereas PMI2 is regulated only by darkness. (iii) Under NaCl, Cu2+, MeJA and wounding stresses, most of the paralogs exhibit different expression patterns. Additionally, GME and GPP are the key regulatory enzymes that limit AsA biosynthesis in response to these treatments. In conclusion, our data support that the conservative and divergent expression patterns of D-Man/L-Gal pathway genes not only avoid AsA biosynthesis network instability but also allow B. rapa to better adapt to complex environments. PMID:27313597

  12. Bacterial intra-species gene loss occurs in a largely clocklike manner mostly within a pool of less conserved and constrained genes

    PubMed Central

    Bolotin, Evgeni; Hershberg, Ruth

    2016-01-01

    Gene loss is a major contributor to the evolution of bacterial gene content. Gene loss may occur as a result of shifts in environment leading to changes in the intensity and/or directionality of selection applied for the maintenance of specific genes. Gene loss may also occur in a more neutral manner, when gene functions are lost that were not subject to strong selection to be maintained, irrespective of changes to environment. Here, we used a pangenome-based approach to investigate patterns of gene loss across 15 bacterial species. We demonstrate that gene loss tends to occur mostly within a pool of genes that are less constrained within species, even in those strains from which they are not lost, and less conserved across bacterial species. Our results indicate that shifts in selection, resulting from shifts in environment are not required to explain the majority of gene loss events occurring within a diverse collection of bacterial species. Caution should therefore be taken when attributing differences in gene content to differences in environment. PMID:27734920

  13. The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

    PubMed

    Chipman, Ariel D; Ferrier, David E K; Brena, Carlo; Qu, Jiaxin; Hughes, Daniel S T; Schröder, Reinhard; Torres-Oliva, Montserrat; Znassi, Nadia; Jiang, Huaiyang; Almeida, Francisca C; Alonso, Claudio R; Apostolou, Zivkos; Aqrawi, Peshtewani; Arthur, Wallace; Barna, Jennifer C J; Blankenburg, Kerstin P; Brites, Daniela; Capella-Gutiérrez, Salvador; Coyle, Marcus; Dearden, Peter K; Du Pasquier, Louis; Duncan, Elizabeth J; Ebert, Dieter; Eibner, Cornelius; Erikson, Galina; Evans, Peter D; Extavour, Cassandra G; Francisco, Liezl; Gabaldón, Toni; Gillis, William J; Goodwin-Horn, Elizabeth A; Green, Jack E; Griffiths-Jones, Sam; Grimmelikhuijzen, Cornelis J P; Gubbala, Sai; Guigó, Roderic; Han, Yi; Hauser, Frank; Havlak, Paul; Hayden, Luke; Helbing, Sophie; Holder, Michael; Hui, Jerome H L; Hunn, Julia P; Hunnekuhl, Vera S; Jackson, LaRonda; Javaid, Mehwish; Jhangiani, Shalini N; Jiggins, Francis M; Jones, Tamsin E; Kaiser, Tobias S; Kalra, Divya; Kenny, Nathan J; Korchina, Viktoriya; Kovar, Christie L; Kraus, F Bernhard; Lapraz, François; Lee, Sandra L; Lv, Jie; Mandapat, Christigale; Manning, Gerard; Mariotti, Marco; Mata, Robert; Mathew, Tittu; Neumann, Tobias; Newsham, Irene; Ngo, Dinh N; Ninova, Maria; Okwuonu, Geoffrey; Ongeri, Fiona; Palmer, William J; Patil, Shobha; Patraquim, Pedro; Pham, Christopher; Pu, Ling-Ling; Putman, Nicholas H; Rabouille, Catherine; Ramos, Olivia Mendivil; Rhodes, Adelaide C; Robertson, Helen E; Robertson, Hugh M; Ronshaugen, Matthew; Rozas, Julio; Saada, Nehad; Sánchez-Gracia, Alejandro; Scherer, Steven E; Schurko, Andrew M; Siggens, Kenneth W; Simmons, DeNard; Stief, Anna; Stolle, Eckart; Telford, Maximilian J; Tessmar-Raible, Kristin; Thornton, Rebecca; van der Zee, Maurijn; von Haeseler, Arndt; Williams, James M; Willis, Judith H; Wu, Yuanqing; Zou, Xiaoyan; Lawson, Daniel; Muzny, Donna M; Worley, Kim C; Gibbs, Richard A; Akam, Michael; Richards, Stephen

    2014-11-01

    Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific

  14. Genome-Wide Gene Expression Profiling Reveals Conserved and Novel Molecular Functions of the Stigma in Rice1[W

    PubMed Central

    Li, Meina; Xu, Wenying; Yang, Wenqiang; Kong, Zhaosheng; Xue, Yongbiao

    2007-01-01

    In angiosperms, the stigma provides initial nutrients and guidance cues for pollen grain germination and tube growth. However, little is known about the genes that regulate these processes in rice (Oryza sativa). Here, we generate rice stigma-specific or -preferential gene expression profiles through comparing genome-wide expression patterns of hand-dissected, unpollinated stigma at anthesis with seven tissues, including seedling shoot, seedling root, mature anther, ovary at anthesis, seeds 5 d after pollination, 10-d-old embryo, 10-d-old endosperm, and suspension-cultured cells by using both 57 K Affymetrix rice whole-genome array and 10 K rice cDNA microarray. A high reproducibility of the microarray results was detected between the two different technology platforms. In total, we identified 548 genes to be expressed specifically or predominantly in the stigma papillar cells of rice. Real-time quantitative reverse transcription-polymerase chain reaction analysis of 34 selected genes all confirmed their stigma-specific expression. The expression of five selected genes was further validated by RNA in situ hybridization. Gene Ontology analysis shows that several auxin-signaling components, transcription, and stress-related genes are significantly overrepresented in the rice stigma gene set. Interestingly, most of them also share several cis-regulatory elements with known stress-responsive genes, supporting the notion of an overlap of genetic programs regulating pollination and stress/defense responses. We also found that genes involved in cell wall metabolism and cellular communication appear to be conserved in the stigma between rice and Arabidopsis (Arabidopsis thaliana). Our results indicate that the stigmas appear to have conserved and novel molecular functions between rice and Arabidopsis. PMID:17556504

  15. The First Myriapod Genome Sequence Reveals Conservative Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima

    PubMed Central

    Chipman, Ariel D.; Ferrier, David E. K.; Brena, Carlo; Qu, Jiaxin; Hughes, Daniel S. T.; Schröder, Reinhard; Torres-Oliva, Montserrat; Znassi, Nadia; Jiang, Huaiyang; Almeida, Francisca C.; Alonso, Claudio R.; Apostolou, Zivkos; Aqrawi, Peshtewani; Arthur, Wallace; Barna, Jennifer C. J.; Blankenburg, Kerstin P.; Brites, Daniela; Capella-Gutiérrez, Salvador; Coyle, Marcus; Dearden, Peter K.; Du Pasquier, Louis; Duncan, Elizabeth J.; Ebert, Dieter; Eibner, Cornelius; Erikson, Galina; Evans, Peter D.; Extavour, Cassandra G.; Francisco, Liezl; Gabaldón, Toni; Gillis, William J.; Goodwin-Horn, Elizabeth A.; Green, Jack E.; Griffiths-Jones, Sam; Grimmelikhuijzen, Cornelis J. P.; Gubbala, Sai; Guigó, Roderic; Han, Yi; Hauser, Frank; Havlak, Paul; Hayden, Luke; Helbing, Sophie; Holder, Michael; Hui, Jerome H. L.; Hunn, Julia P.; Hunnekuhl, Vera S.; Jackson, LaRonda; Javaid, Mehwish; Jhangiani, Shalini N.; Jiggins, Francis M.; Jones, Tamsin E.; Kaiser, Tobias S.; Kalra, Divya; Kenny, Nathan J.; Korchina, Viktoriya; Kovar, Christie L.; Kraus, F. Bernhard; Lapraz, François; Lee, Sandra L.; Lv, Jie; Mandapat, Christigale; Manning, Gerard; Mariotti, Marco; Mata, Robert; Mathew, Tittu; Neumann, Tobias; Newsham, Irene; Ngo, Dinh N.; Ninova, Maria; Okwuonu, Geoffrey; Ongeri, Fiona; Palmer, William J.; Patil, Shobha; Patraquim, Pedro; Pham, Christopher; Pu, Ling-Ling; Putman, Nicholas H.; Rabouille, Catherine; Ramos, Olivia Mendivil; Rhodes, Adelaide C.; Robertson, Helen E.; Robertson, Hugh M.; Ronshaugen, Matthew; Rozas, Julio; Saada, Nehad; Sánchez-Gracia, Alejandro; Scherer, Steven E.; Schurko, Andrew M.; Siggens, Kenneth W.; Simmons, DeNard; Stief, Anna; Stolle, Eckart; Telford, Maximilian J.; Tessmar-Raible, Kristin; Thornton, Rebecca; van der Zee, Maurijn; von Haeseler, Arndt; Williams, James M.; Willis, Judith H.; Wu, Yuanqing; Zou, Xiaoyan; Lawson, Daniel; Muzny, Donna M.; Worley, Kim C.; Gibbs, Richard A.; Akam, Michael; Richards, Stephen

    2014-01-01

    Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific

  16. Inheritance and testicular cancer.

    PubMed Central

    Nicholson, P. W.; Harland, S. J.

    1995-01-01

    Statistical analysis of published data on the age of onset of germ cell tumours of the testis and of the prevalence of bilateral disease in familial and general cases suggest the following: 1. Patients with bilateral disease carry the same genetic predisposition as familial cases. 2. Males with the hereditary predisposition develop none, unilateral or bilateral tumours in the proportions 55%, 38% and 7% respectively. 3. One-third of all testis cancer patients are genetically predisposed to the disease. 4. The 2.2% risk to brothers of cases as reported elsewhere can be accounted for by the homozygous (recessive) inheritance of a single predisposing gene. PMID:7841065

  17. Subfertility and Risk of Testicular Cancer in the EPSAM Case-Control Study

    PubMed Central

    Zugna, Daniela; Fiano, Valentina; Robles Rodriguez, Nena; Maule, Milena; Gillio-Tos, Anna; Ciuffreda, Libero; Lista, Patrizia; Segnan, Nereo; Merletti, Franco; Richiardi, Lorenzo

    2016-01-01

    Background/objectives It has been suggested that subfertility and testicular cancer share genetic and environmental risk factors. We studied both subfertility and the strongest known testicular cancer susceptibility gene, the c-KIT ligand (KITLG), whose pathway is involved in spermatogenesis. Methods The EPSAM case-control study is comprised of testicular cancer patients from the Province of Turin, Italy, diagnosed between 1997 and 2008. The present analysis included 245 cases and 436 controls from EPSAM, who were aged 20 years or older at diagnosis/recruitment. The EPSAM questionnaire collected information on factors such as number of children, age at first attempt to conceive, duration of attempt to conceive, use of assisted reproduction techniques, physician-assigned diagnosis of infertility, number of siblings, and self-reported cryptorchidism. Genotyping of the KITLG single nucleotide polymorphism (SNP) rs995030 was performed on the saliva samples of 202 cases and 329 controls. Results Testicular cancer was associated with the number of children fathered 5 years before diagnosis (odds ratio (OR) per additional child: 0.78, 95% confidence interval (CI): 0.58–1.04) and sibship size (OR per additional sibling: 0.76, 95% CI: 0.66–0.88). When considering the reproductive history until 1 year before diagnosis, attempting to conceive for at least 12 months or fathering a child using assisted reproduction techniques was not associated with the risk of testicular cancer, nor was age at first attempt to conceive or physician-assigned diagnosis of infertility. The SNP rs995030 was strongly associated with risk of testicular cancer (per allele OR: 1.83; 95%CI: 1.26–2.64), but it did not modify the association between number of children and the risk of testicular cancer. Conclusion This study supports the repeatedly reported inverse association between number of children and risk of testicular cancer, but it does not find evidence of an association for other

  18. Circadian expression of the maize catalase Cat3 gene is highly conserved among diverse maize genotypes with structurally different promoters.

    PubMed Central

    Polidoros, A N; Scandalios, J G

    1998-01-01

    The Cat3 gene of maize exhibits a transcriptionally regulated circadian rhythm. In the present study we examined the following: (1) the extent of the circadian Cat3 expression between maize genotypes of diverse origin; (2) the functional significance of a Tourist transposable element located in the Cat3 promoter of the inbred line W64A, which harbors putative regulatory elements (GATA repeat, CCAAT boxes) shown to be involved in the light induction and circadian regulation of the Arabidopsis CAB2, as well as other plant genes; and (3) aspects of the physiological role of CAT-3 in maize metabolism. Results confirm that the circadian Cat3 expression is a general phenomenon in maize. Regulation of Cat3 gene expression is not dependent on the presence of the Tourist element in the promoter of the gene nor on the presence of motifs similar to those found significant in the circadian expression of the Arabidopsis CAB2 gene. Structural diversity was revealed in the Cat3 promoters of maize genotypes of diverse origins. However, highly conserved regions with putative regulatory motifs were identified. Relevance of the conserved regions to the circadian regulation of the gene is discussed. Possible physiological roles of CAT-3 are suggested. PMID:9584112

  19. CPU86017-RS attenuate hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines

    PubMed Central

    Zhang, Guo-lin; Yu, Feng; Dai, De-zai; Cheng, Yu-si; Zhang, Can; Dai, Yin

    2012-01-01

    Aim: Downregulation of androgen biosynthesis genes StAR (steroidogenic acute regulatory) and 3β-HSD (3β-hydroxysteroid dehydrogenase) contributes to low testosterone levels in hypoxic mice and is possibly related to increased expression of pro-inflammatory cytokines in the testis. The aim of this study is to investigate the effects of CPU86017-RS that block Ca2+ influx on hypoxia-induced testis insult in mice. Methods: Male ICR mice were divided into 5 groups: control group, hypoxia group, hypoxia group treated with nifedipine (10 mg/kg), hypoxia groups treated with CPU86017-RS (60 or 80 mg/kg). Hypoxia was induced by placing the mice in a chamber under 10%±0.5% O2 for 28 d (8 h per day). The mice were orally administered with drug in the last 14 d. At the end of experiment the testes of the mice were harvested. The mRNA and protein levels of StAR, 3β-HSD, connexin 43 (Cx43), matrix metalloprotease 9 (MMP9), endothelin receptor A (ETAR) and leptin receptor (OBRb) were analyzed using RT-PCR and Western blotting, respectively. The malondialdehyde (MDA), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) levels were measured using biochemical kits. Serum testosterone concentration was measured with radioimmunoassay. Results: Hypoxia significantly increased the MDA level, and decreased the LDH, ACP and SDH activities in testes. Meanwhile, hypoxia induced significant downregulation of StAR and 3β-HSD in testes responsible for reduced testosterone biosynthesis. It decreased the expression of Cx43, and increased the expression of MMP9, ETAR and OBRb, leading to abnormal testis function and structure. These changes were effectively diminished by CPU86017-RS (80 mg/kg) or nifedipine (10 mg/kg). Conclusion: Low plasma testosterone level caused by hypoxia was due to downregulation of StAR and 3β-HSD genes, in association with an increased expression of pro-inflammatory cytokines. These changes can be alleviated by CPU86017-RS or

  20. Suppression subtractive hybridization (SSH) for isolation and characterization of genes related to testicular development in the giant tiger shrimp Penaeus monodon.

    PubMed

    Leelatanawit, Rungnapa; Klinbunga, Sirawut; Aoki, Takashi; Hirono, Ikuo; Valyasevi, Rudd; Menasveta, Piamsak

    2008-11-30

    Suppression subtractive hybridization (SSH) cDNA libraries of the giant tiger shrimp, Penaeus monodon, were constructed. In total, 178 and 187 clones from the forward and reverse SSH libraries, respectively, of P. monodon were unidirectionally sequenced. From these, 37.1% and 53.5% Expressed Sequence Tags (ESTs) significantly matched known genes (E-value < 1e-04). Three isoforms of P. monodon progestin membrane receptor component 1: PM-PGMRC1-s (1980 bp), PM-PGMRC1-m (2848 bp), and PM-PGMRC1-l (2971 bp), with an identical ORF of 573 bp corresponding to a deduced polypeptide of 190 amino acids, were successfully identified by RACE-PCR. Interestingly, PMPGMRC1 showed a greater expression level in testes of juvenile than broodstock P. monodon (P < 0.05). Dopamine administration (10(-6) mol/shrimp) resulted in up-regulation of PMPGMRC1 in testes of juveniles at 3 hrs post treatment (P < 0.05), but had no effect on PM-Dmc1 (P > 0.05).

  1. Testicular cancer health education: an integrative review.

    PubMed

    Rosella, J D

    1994-10-01

    Cancer of the testis is the most common malignancy in men between the ages of 15 and 35, yet it is one of the most curable cancers. The optimistic prognosis that results from early detection and treatment of testicular cancer underscores the critical need for teaching testicular self-examination (TSE). However, an integrative review of the health education literature suggests that the men most susceptible are virtually unaware of the symptoms of testicular cancer and how to detect them. Although educational materials have been available, very little intervention research has been published on testicular cancer. The literature to date has focused on the pyschosocial factors associated with the practice of TSE and increasing knowledge of testicular cancer. Although an important beginning step, knowledge of testicular cancer alone as a preventive health behaviour is not sufficient if young men either do not know how to do the examination on their own testicles or do not believe it is important to them. Nurses should incorporate health education for testicular cancer and TSE in the delivery of routine primary health care. Furthermore, future research should aim to (a) increase knowledge through the educational curricula of high schools and colleges by use of video presentations, (b) examine the efficacy of using silicone models to ensure that men can be trained to detect the symptoms of testicular cancer, and (c) study compliance with recommendations to perform TSE.

  2. Testicular Cancer Education in the Classroom.

    ERIC Educational Resources Information Center

    Wohl, Royal E.

    1998-01-01

    Testicular cancer (TC) education is not widespread, though TC is the most common cancer in men ages 15-34 years. Teachers can positively influence young men by providing TC and testicular self-examination (TSE) education in school. The paper describes TC and TSE, discussing strategies for and barriers to implementation of TC/TSE instruction in the…

  3. 21 CFR 876.3750 - Testicular prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Testicular prosthesis. 876.3750 Section 876.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3750 Testicular prosthesis. (a...

  4. 21 CFR 876.3750 - Testicular prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Testicular prosthesis. 876.3750 Section 876.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Prosthetic Devices § 876.3750 Testicular prosthesis. (a...

  5. G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    USDA-ARS?s Scientific Manuscript database

    In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...

  6. Promoter analysis of intestinal genes induced during iron-deprivation reveals enrichment of conserved SP1-like binding sites

    PubMed Central

    Collins, James F; Hu, Zihua

    2007-01-01

    Background Iron-deficiency leads to the induction of genes related to intestinal iron absorption and homeostasis. By analyzing a large GeneChip® dataset from the rat intestine, we identified a large cluster of 228 genes that was induced by iron-deprivation. Only 2 of these genes contained 3' iron-response elements, suggesting that other regulation including transcriptional may be involved. We therefore utilized computational methods to test the hypothesis that some of the genes within this large up-regulated cluster are co-ordinately regulated by common transcriptional mechanisms. We thus identified promoters from the up-regulated gene cluster from rat, mouse and human, and performed enrichment analyses with the Clover program and the TRANSFAC database. Results Surprisingly, we found a strong statistical enrichment for SP1 binding sites in our experimental promoters as compared to background sequences. As the TRANSFAC database cannot distinguish among SP/KLF family members, many of which bind similar GC-rich DNA sequences, we surmise that SP1 or an SP1-like factor could be involved in this response. In fact, we detected induction of SP6/KLF14 in the GeneChip® studies, and confirmed it by real-time PCR. Additional computational analyses suggested that an SP1-like factor may function synergistically with a FOX TF to regulate a subset of these genes. Furthermore, analysis of promoter sequences identified many genes with multiple, conserved SP1 and FOX binding sites, the relative location of which within orthologous promoters was highly conserved. Conclusion SP1 or a closely related factor may play a primary role in the genetic response to iron-deficiency in the mammalian intestine. PMID:18005439

  7. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes.

    PubMed

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    Spermatogenesis, a study of germ cell development, is a long, orderly, and well-defined process occurring in seminiferous tubules of the testis. It is a temporal event whereby undifferentiated spermatogonial germ cells evolve into maturing spermatozoa over a period of several weeks. Spermatogenesis is characterized by three specific functional phases: proliferation, meiosis, and differentiation, and it involves spermatogonia, spermatocytes, and spermatids. Germ cells at steps of development form various cellular associations or stages, with 6, 12, and 14 specific stages being identified in human, mouse, and rat, respectively. The stages evolve over time in a given area of the seminiferous tubule forming a cycle of the seminiferous epithelium that has a well-defined duration for a given species. In this part, we discuss the proliferation and meiotic phase whereby spermatogonia undergo several mitotic divisions to form spermatocytes that undergo two meiotic divisions to form haploid spermatids. In the rat, spermatogonia can be subdivided into several classes: stem cells (A(s)), proliferating cells (A(pr), A(al)), and differentiating cells (A(1)-A(4), In, B). They are dependent on a specific microenvironment (niche) contributed by Sertoli, myoid, and Leydig cells for proper development. Spermatogonia possess several surface markers whereby they can be identified from each other. During meiosis, spermatocytes undergo chromosomal pairing, synapsis, and genetic exchang