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261.
The pea aphid genome was recently found to harbor genes for carotenoid biosynthesis, reflecting an ancestral transfer from a fungus. To explore the evolution of the carotene desaturase gene family within aphids, sequences were retrieved from a set of 34 aphid species representing numerous deeply diverging lineages of aphids and analyzed together with fungal sequences retrieved from databases. All aphids have at least one copy of this gene and some aphid species have up to seven, whereas fungal genomes consistently have a single copy. The closest relatives of aphids, adelgids, also have carotene desaturase; these sequences are most closely related to those from aphids, supporting a shared origin from a fungal to insect transfer predating the divergence of adelgids and aphids. Likewise, all aphids, and adelgids, have carotenoid profiles that are consistent with their biosynthesis using the acquired genes of fungal origin rather than derivation from food plants. The carotene desaturase was acquired from a fungal species outside of Ascomycota or Basidiomycota and closest to Mucoromycotina among sequences available in databases. In aphids, an ongoing pattern of gene duplication is indicated by the presence of both anciently and recently diverged paralogs within genomes and by the presence of a high frequency of pseudogenes that appear to be recently inactivated. Recombination among paralogs is evident, making analyses of patterns of selection difficult, but tests of selection for a nonrecombining region indicates that duplications tend to be followed by bouts of positive selection. Species of Macrosiphini, which often show color polymorphisms, typically have a larger number of desaturase copies relative to other species sampled in the study. These results indicate that aphid evolution has been accompanied by ongoing evolution of carotenogenic genes, which have undergone duplication, recombination, and occasional positive selection to yield a wide variety of carotenoid profiles in different aphid species. 相似文献
262.
Miller JP Yeh N Hofstetter CP Keskin D Goldstein AS Koff A 《The Journal of biological chemistry》2012,287(24):19775-19785
SV40 small t-antigen (ST) collaborates with SV40 large T-antigen (LT) and activated rasv12 to promote transformation in a variety of immortalized human cells. A number of oncogenes or the disruption of the general serine-threonine phosphatase protein phosphatase 2A (PP2A) can replace ST in this paradigm. However, the relationship between these oncogenes and PP2A activity is not clear. To address this, we queried the connectivity of these molecules in silico. We found that p27 was connected to each of those oncogenes that could substitute for ST. We further determined that p27 loss can substitute for the expression of ST during transformation of both rodent and human cells. Conversely, knock-in cells expressing the degradation-resistant S10A and T187A mutants of p27 were resistant to the transforming activities of ST. This suggests that p27 is an important target of the tumor-suppressive effects of PP2A and likely an important target of the multitude of cellular oncoproteins that emulate the transforming function of ST. 相似文献
263.
BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair 总被引:1,自引:0,他引:1
Bunting SF Callén E Kozak ML Kim JM Wong N López-Contreras AJ Ludwig T Baer R Faryabi RB Malhowski A Chen HT Fernandez-Capetillo O D'Andrea A Nussenzweig A 《Molecular cell》2012,46(2):125-135
Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice and rescues HR deficiency, as measured by hypersensitivity to polyADP-ribose polymerase (PARP) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), indicating that BRCA1 has an additional role in DNA crosslink repair that is distinct from HR. Disruption of the nonhomologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2 provides a key activity that cannot be bypassed by ablation of 53BP1 or Ku. 相似文献
264.
Monica J. Justice Bebra J. Gilbert Kenneth W. Kinzler Bert Vogelstein Authur M. Buchberg Jeffrey D. Ceci Yoichi Matsuda Verne M. Chapman Christos Patriotis Antonios Makris Philip N. Tsichlis Nancy A. Jenkins Neal G. Copeland 《Genomics》1992,13(4):1281-1288
An interspecific backcross between C57BL/6J and Mus spretus was used to generate a molecular genetic linkage map of mouse chromosome 18 that includes 23 molecular markers and spans approximately 86% of the estimated length of the chromosome. The Apc, Camk2a, D18Fcr1, D18Fcr2, D18Leh1, D18Leh2, Dcc, Emb-rs3, Fgfa, Fim-2/Csfmr, Gnal, Grl-1, Grp, Hk-1rs1, Ii, Kns, Lmnb, Mbp, Mcc, Mtv-38, Palb, Pdgfrb, and Tpl-2 genes were mapped relative to each other in one interspecific backcross. A second interspecific backcross and a centromere-specific DNA satellite probe were used to determine the distance of the most proximal chromosome 18 marker to the centromere. The interspecific map extends the known regions of linkage homology between mouse chromosome 18 and human chromosomes 5 and 18 and identifies a new homology segment with human chromosome 10p. It also provides molecular access to many regions of mouse chromosome 18 for the first time. 相似文献
265.
Young SF Tatter SB Valego NK Figueroa JP Thompson J Rose JC 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,284(6):R1621-R1630
Corticotropin-releasing hormone receptor type 1 (CRH-R1) expression and vasopressin type 1b (V1b) receptor protein decrease in late-gestation fetal sheep. Because hypothalamo-pituitary disconnection (HPD) has been demonstrated to prevent the morphological maturation of corticotrophs, we hypothesized that hypothalamic input is necessary for the maturational changes in CRH-R1 and V1b receptor levels. We measured CRH-R1 and V1b receptor expression in the anterior pituitaries of fetuses at 140 days gestational age (dGA) that underwent HPD or sham surgery at 120 dGA. CRH-R1 mRNA decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. However, CRH-R1 protein levels were elevated in HPD fetuses compared with sham and were not different from 120 dGA values. V1b protein levels decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. We conclude that hypothalamic input to the pituitary is necessary for the decrease in CRH-R1 receptor protein levels in late-gestation fetal sheep. However, hypothalamic input is not necessary for the decrease in V1b receptor expression seen in late gestation. 相似文献
266.
Andrea Ganna Fernando Rivadeneira Albert Hofman André G. Uitterlinden Patrik K. E. Magnusson Nancy L. Pedersen Erik Ingelsson Henning Tiemeier 《Human genetics》2013,132(5):553-561
Twin studies have estimated the heritability of longevity to be approximately 20–30 %. Genome-wide association studies (GWAS) have revealed a large number of determinants of morbidity, but so far, no new polymorphisms have been discovered to be associated with longevity per se in GWAS. We aim to determine whether the genetic architecture of mortality can be explained by single nucleotide polymorphisms (SNPs) associated with common traits and diseases related to mortality. By extensive quality control of published GWAS we created a genetic score from 707 common SNPs associated with 125 diseases or risk factors related with overall mortality. We prospectively studied the association of the genetic score with: (1) time-to-death; (2) incidence of the first of nine major diseases (coronary heart disease, stroke, heart failure, diabetes, dementia, lung, breast, colon and prostate cancers) in two population-based cohorts of Dutch and Swedish individuals (N = 15,039; age range 47–99 years). During a median follow-up of 6.3 years (max 22.2 years), we observed 4,318 deaths and 2,132 incident disease events. The genetic score was significantly associated with time-to-death [hazard ratio (HR) per added risk allele = 1.003, P value = 0.006; HR 4th vs. 1st quartile = 1.103]. The association between the genetic score and incidence of major diseases was stronger (HR per added risk allele = 1.004, P value = 0.002; HR 4th vs. 1st quartile = 1.160). Associations were stronger for individuals dying at older ages. Our findings are compatible with the view of mortality as a complex and highly polygenetic trait, not easily explainable by common genetic variants related to diseases and physiological traits. 相似文献
267.
Obesity in Adolescence Predicts Lower Educational Attainment and Income in Adulthood: The Project EAT Longitudinal Study 下载免费PDF全文
Simone A. French Melanie Wall Thomas Corbeil Nancy E. Sherwood Jerica M. Berge Dianne Neumark‐Sztainer 《Obesity (Silver Spring, Md.)》2018,26(9):1467-1473
Objective
Prospective associations between obesity in adolescence and adult socioeconomic outcomes, and potential mediators, were examined in a contemporary cohort.Methods
Longitudinal data collected in 1998 to 1999 (Project EAT‐I) and 2015 to 2016 (EAT‐IV) were analyzed for 1,796 participants who provided data at both time points. Adolescents (mean age = 14.8 years) self‐reported demographic and psychosocial variables (EAT‐I) and follow‐up outcomes (EAT‐IV). Body weight and height were directly measured. Bachelor's degree or more education, income ≥ US $50,000, and partnered status at follow‐up were examined by baseline obesity (>95th BMI percentile) using logistic regression. Self‐esteem, depression, and weight‐related teasing were examined as mediators using multivariate probit regressions. All analyses were adjusted for race, baseline age, and parent socioeconomic status.Results
Girls with obesity were significantly less likely to have achieved a bachelor’s degree (OR 0.32, 95% CI [0.18, 0.58]; P < 0.001), earn ≥ $50,000 annually (OR 0.57, 95% CI [0.33, 0.99]; P < 0.04), or be partnered (OR 0.45, 95% CI [0.27, 0.75]; P < 0.002) in adulthood. No associations were observed among boys. Among girls, depression mediated 8.5% and 23.6% of the association between adolescent obesity and adult education and income, respectively.Conclusions
Adolescent girls with obesity have lower educational attainment and income and are less likely to be partnered in later adulthood. Depression may partly mediate the associations.268.
Most pathogenic Proteus species are primarily associated with urinary tract infections, especially in persons with indwelling catheters or functional/anatomic abnormalities of the urinary tract. Urinary tract infections caused by Proteus vulgaris typically form biofilms and are resistant to commonly used antibiotics. The Rts1 conjugative plasmid from a clinical isolate of P. vulgaris carries over 300 predicted open reading frames, including antibiotic resistance genes. The maintenance of the Rts1 plasmid is ensured in part by the HigBA toxin-antitoxin system. We determined the precise mechanism of action of the HigB toxin in vivo, which is distinct from other known toxins. We demonstrate that HigB is an endoribonuclease whose enzymatic activity is dependent on association with ribosomes through the 50 S subunit. Using primer extension analysis of several test mRNAs, we showed that HigB cleaved extensively across the entire length of coding regions only at specific recognition sequences. HigB mediated cleavage of 100% of both in-frame and out-of-frame AAA sequences. In addition, HigB cleaved ∼20% of AA sequences in coding regions and occasionally cut single As. Remarkably, the cleavage specificity of HigB coincided with one of the most frequently used codons in the AT-rich Proteus spp., AAA (lysine). Therefore, the HigB-mediated plasmid maintenance system for the Rts1 plasmid highlights the intimate relationship between host cells and extrachromosomal DNA that enables the dynamic acquisition of genes that impart a spectrum of survival advantages, including those encoding multidrug resistance and virulence factors.Toxin-antitoxin (TA)3/addiction/suicide modules typically include an autoregulated operon encoding a labile antitoxin and a more stable toxic protein (1). TA toxins facilitate stress survival (chromosomal) or plasmid maintenance and post-segregational killing (extrachromosomal; reviewed in Refs. 1, 2). Most chromosomal TA toxins inhibit cell growth by reversibly targeting either protein translation or DNA replication; their cognate antitoxins prevent toxin activity during periods of optimal growth but enable finely tuned control of TA module toxicity during relatively short periods of environmental stress. However, prolonged stress leads to a point of no return and cell death (3–5).There are six confirmed chromosomal TA loci in Escherichia coli K12 cells: dinJ-yafQ, relBE, yefM-yoeB, mazEF, chpBI-BK, and hipBA. The toxins MazF and ChpBK are sequence-specific endoribonucleases that cleave free mRNA (6–10). The RelE toxin interacts with the ribosome and induces mRNA cleavage with a preference for the UAG stop codon (11–13). The YafQ toxin is a ribosome-associated endoribonuclease that cleaves in-frame AAA codons that are followed by either an A or G in the subsequent codon (14). The YoeB toxin inhibits translation at the initiation step, apparently by destabilization of the initiation complex (15). HipA toxin is a kinase whose mechanism of action is not known (16, 17).Although the mechanism of action of many E. coli chromosomal and plasmid-derived toxins has been determined, the precise function of the HigB toxin has not been characterized. The higBA TA module is not present in E. coli K12; it resides on the Rts1 plasmid that typically replicates in Proteus spp. and imparts kanamycin resistance as well as temperature-sensitive post-segregational killing at 42 °C (18, 19). Interestingly, one or more chromosomal counterparts of higBA have been reported for several pathogens, including Vibrio cholerae, Streptococcus pneumoniae, E. coli CFT073, and E. coli O157:H7 (20). Some characterization of the two V. cholerae HigBA modules has been performed. First, one of the two higBA modules was shown to possess the general characteristics of TA systems by demonstration of toxin-antitoxin interaction, module organization/regulation, HigB toxicity, and rescue of toxicity with the cognate HigA antitoxin (21). Overexpression of HigB derived from two individual higBA modules encoded in V. cholerae or from Rts1 leads to inhibition of protein synthesis through translation-dependent mRNA cleavage in a manner similar to, but distinct from, RelE (22).HigB is a member of the RelE family of toxins, including RelE, YafQ, and YoeB (20). In this study, we have identified the precise mode of action of HigB from Rts1. HigB associated with the 50 S ribosomal subunit, and this HigB-ribosome complex cleaved within mRNA coding regions at all AAA triplet sequences, both in-frame and out-of-frame. HigB appeared to be responsible for the mRNA cleavage activity of the HigB-ribosome complex because a HigB H92Q mutant lacked mRNA cleavage activity but remained associated with the ribosome. Finally, the cleavage specificity of HigB on plasmid Rts1 coincided with the sequence (AAA, lysine) of either the most abundant or the second most abundant codon in its Proteus host. 相似文献
269.
Carlos F. Solis Julien Santi-Rocca Doranda Perdomo Christian Weber Nancy Guillén 《PloS one》2009,4(12)
Background
Modern RNA interference (RNAi) methodologies using small interfering RNA (siRNA) oligonucleotide duplexes or episomally synthesized hairpin RNA are valuable tools for the analysis of gene function in the protozoan parasite Entamoeba histolytica. However, these approaches still require time-consuming procedures including transfection and drug selection, or costly synthetic molecules.Principal Findings
Here we report an efficient and handy alternative for E. histolytica gene down-regulation mediated by bacterial double-stranded RNA (dsRNA) targeting parasite genes. The Escherichia coli strain HT115 which is unable to degrade dsRNA, was genetically engineered to produce high quantities of long dsRNA segments targeting the genes that encode E. histolytica β-tubulin and virulence factor KERP1. Trophozoites cultured in vitro were directly fed with dsRNA-expressing bacteria or soaked with purified dsRNA. Both dsRNA delivery methods resulted in significant reduction of protein expression. In vitro host cell-parasite assays showed that efficient downregulation of kerp1 gene expression mediated by bacterial dsRNA resulted in significant reduction of parasite adhesion and lytic capabilities, thus supporting a major role for KERP1 in the pathogenic process. Furthermore, treatment of trophozoites cultured in microtiter plates, with a repertoire of eighty-five distinct bacterial dsRNA segments targeting E. histolytica genes with unknown function, led to the identification of three genes potentially involved in the growth of the parasite.Conclusions
Our results showed that the use of bacterial dsRNA is a powerful method for the study of gene function in E. histolytica. This dsRNA delivery method is also technically suitable for the study of a large number of genes, thus opening interesting perspectives for the identification of novel drug and vaccine targets. 相似文献270.
Thomas Pavelitz Lindsay Renfro Nathan R. Foster Amber Caracol Piri Welsch Victoria Valinluck Lao William B. Grady Donna Niedzwiecki Leonard B. Saltz Monica M. Bertagnolli Richard M. Goldberg Peter S. Rabinovitch Mary Emond Raymond J. Monnat Jr Nancy Maizels 《PloS one》2014,9(10)