The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis

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Identification of up-regulated genes in human uterine leiomyoma by suppression subtractive hybridization

In searching for differentially expressed genes in human uterine leiomyomas (ULs), suppression sub-tractive hybridization was used to construct an UL up-regulated library, which turned out to represent 88genes. After two rounds of screening by reverse Northern analysis, twenty genes were proved to be up-regulated, including seventeen known genes and three genes with unknown function. All these genes werefirstly associated with UL. Three genes with notable difference were selected for Northern confirmationOur results proved the authenticity of the twenty genes. One gene named Phospholipase A2 (PLA2) showedup-regulation in 4/6 of the patients and investigation of tissue distribution indicated that it had obviousexpression in prostate, testis, liver, heart and skeletal muscle.     

Sociosexual development,pair bond formation,and mechanisms of fertility suppression in female cotton-top tamarins (Saguinus oedipus oedipus)

The effect of various social environments on sociosexual behavior was examined in six young female cotton-top tamarins (Saguinus oedipus oedipus) and in three established breeding females. Behavioral observations and hormonal samples were collected on young females while they were living with their families, when they were isolated from conspecifics, and after they were paired with an unrelated male. While living with the family, all females showed a suppression of fertility and low frequencies of sociosexual behavior. Following removal from the family, isolated females displayed an increase in rate of scent marking and an increase in hormonal levels. When young females were paired with males, they were exposed to scent secretions from their natal families, from an unfamilar family, and from a control for a total of 24 weeks. After pairing, hormonal levels increased dramatically, and ovarian cyclicity began. An increase in sociosexual behavior and elevated levels of scent marking accompanied this physiological change. Newly paired females had higher rates of affiliative behavior and scent marking than did established breeding females. However, both newly paired and established breeding males were more likely to initiate contact, grooming bouts, and social sniffing than were females. Time to first ovulation was later in females who were exposed to scent secretions from their natal families than it was in those females given a control for the first 8 weeks following pairing. No female conceived during exposure to scent secretions. However, once normal ovarian cycling had begun or a pregnancy was established, exposure to scent secretions had no effect. Thus, the social environment influences the fertility, sociosexual behavior, and pair bond formation of cotton-top tamarins. In addition, chemical stimuli found in the scent secretions produced by the natal family are most likely involved in reproductive suppression.     

Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function

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Effect of hyperoxidized guanine on DNA primer-template structures: Spiroiminodihydantoin leads to strand slippage

Oxidation of guanine in DNA can lead to mutagenic lesions such as 7-hydro-8-oxoguanine (oG). Upon further oxidation, a more mutagenic lesion, spirominodihydantoin (Sp), can occur. In this study, nuclear magnetic resonance (NMR) investigations were performed to determine the structural features of DNA primer-template models with 5′-GG, 5′-G(oG), 5′-G(Sp) and 5′-T(Sp) templates, that mimic the situation in which the downstream G of the template has been oxidized to oG or hyperoxidized to Sp. Our results show that misalignment occurs only in the 5′-G(Sp) and 5′-T(Sp) templates, providing structural insights into the observed differences in mutagenicity of Sp and oG during DNA replication.     

Plant Sources of Chinese Herbal Remedies: Effects on Pratylenchus vulnus and Meloidogyne javanica

More than 500 plant species, used alone or in combination, are documented in Chinese traditional medicine to have activity against helminth and micro-invertebrate pests of humans. We subjected 153 candidate medicines or their plant sources to multilevel screening for effectiveness against plant-parasitic nematodes. For extracts effective in preliminary screens, we determined time-course and concentration-response relationships. Seventy-three of the aqueous extracts of medicines or their plant sources killed either Meloidogyne javanica juveniles or Pratylenchus vulnus (mixed stages), or both, within a 24-hour exposure period. Of 64 remedies reported as antihelminthics, 36 were effective; of 21 classi- fied as purgatives, 13 killed the nematodes; of 29 indicated as generally effective against pests, 13 killed the nematodes. Sources of extracts effective against one or both species of plant-parasitic nematodes are either the whole plant or vegetative, storage or reproductive components of the plants. Effective plants include both annuals and perennials, range from grasses and herbs to woody trees, and represent 46 plant families.     

Development of mating disruption for control of pine sawfly populations

Mating disruption of the pine sawflyNeodiprion sertifer (Geoffroy) (Hymenoptera: Diprionidae) was strongly indicated by reduced male trap catches in pine plantations permeated with the sex phermone, (2S, 3S, 7S)-diprionly acetate. The trap catch reduction was 95 to near 100% when dispensers every 10 m were used, giving a total release of about 3 mg per hectare and day. Two mg of pheromone per cotton roll dispenser maintained low catches for the whole season (about 2 months) without any renewal of disruption dispensers. Anerythro-mixture was as effective as the pure pheromone isomer. The effects of the experiments on population density and sex ratio were not possible to investigate, due to a general collapse of the population, also outside experimental plots, the year after the experiments.     

miR-34a is essential for p19Arf-driven cell cycle arrest

The Arf tumor suppressor gene product, p19^Arf, regulates cell proliferation in incipient cancer cells and during embryo development. Beyond its commonly accepted p53-dependent actions, p19^Arf also acts independently of p53 in both contexts. One such p53-independent effect with in vivo relevance includes its repression of Pdgfrβ, a process that is essential for vision in the mouse. We have utilized cell culture-based and mouse models to define a new role for miR-34a in this process. Ectopic expression of Arf in cultured cells enhanced the expression of several microRNAs predicted to target Pdgfrß synthesis, including the miR-34 family. Because miR-34a has been implicated as a p53-dependent effector, we investigated whether it also contributed to p53-independent effects of p19^Arf. Indeed, in mouse embryo fibroblasts (MEFs) lacking p53, Arf-driven repression of Pdgfrβ and its blockade of Pdgf-B stimulated DNA synthesis were both completely interrupted by anti-microRNA against miR-34a. Ectopic miR-34a directly targeted Pdgfrβ and a plasmid reporter containing wild-type Pdgfrβ 3′UTR sequence, but not one in which the miR-34a target sequence was mutated. Although miR-34a expression has been linked to p53—a well-known effector of p19^Arf—Arf expression and its knockdown correlated with miR-34a level in MEFs lacking p53. Finally, analysis of the mouse embryonic eye demonstrated that Arf controlled expression of miR-34a, and the related miR-34b and c, in vivo during normal mouse development. Our findings indicate that miR-34a provides an essential link between p19^Arf and its p53-independent capacity to block cell proliferation driven by Pdgfrβ. This has ramifications for developmental and tumor suppressor roles of Arf.