Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules That Affect Aging Pathways and Extend Caenorhabditis elegans' Lifespan.

Increased resistance to environmental stress at the cellular level is correlated with the longevity of long-lived mutants and wild-animal species. Moreover, in experimental organisms, screens for increased stress resistance have yielded mutants that are long-lived. To find entry points for small molecules that might extend healthy longevity in humans, we screened ∼100,000 small molecules in a human primary-fibroblast cell line and identified a set that increased oxidative-stress resistance. Some of the hits fell into structurally related chemical groups, suggesting that they may act on common targets. Two small molecules increased C. elegans' stress resistance, and at least 9 extended their lifespan by ∼10-50%. We further evaluated a chalcone that produced relatively large effects on lifespan and were able to implicate the activity of two, stress-response regulators, NRF2/skn-1 and SESN/sesn-1, in its mechanism of action. Our findings suggest that screening for increased stress resistance in human cells can enrich for compounds with promising pro-longevity effects. Further characterization of these compounds may reveal new ways to extend healthy human lifespan

Effects of magnetic field on thermo-hydraulic performance of Fe3O4-water nanofluids in a corrugated tube

© 2018 Elsevier Ltd An experimental system is established to investigate the thermo-hydraulic performance of Fe3O4-water nanofluids in a corrugated tube under various magnetic fields. The influences of magnetic induction intensities (B = 0 G, 100 G, 200 G, 300 G), nanoparticle mass fractions (ω = 0.0%, 0.1%, 0.3%, 0.5%), electromagnet arrangement modes (one-side electromagnet and two-side staggered electromagnet), kinds of tubes (smooth tube and corrugated tube), Reynolds numbers (Re = 800–12,000) on flow and heat transfer characteristics are discussed. It is obtained that the augmentation of heat transfer is more sensitive to high nanoparticle mass fraction, high magnetic induction intensity, two-side staggered electromagnet and corrugated tube. A Comprehensive evaluation index is applied to estimate the thermo-hydraulic performance. It can be discovered that the comprehensive evaluation index increases with the increasing Reynolds number at first and then decreases, and the rough surface of corrugated tube delays the appearance of critical Reynolds number

USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency

The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). Stabilization of Nanog proteins is essential for ESCs. The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions. Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated, the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined. In this study, we identify the ubiquitin-specific peptidase 21 (USP21) as a deubiquitylase for Nanog, but not for Oct4 or Sox2. USP21 interacts with Nanog protein in ESCs in vivo and in vitro. The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction. USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog, stabilizing Nanog. USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs. Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation. Overall, our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog

A cold high-pressure system over North China hinders the southward migration of Mythimna separata in autumn

Background In warm regions or seasons of the year, the planetary boundary layer is occupied by a huge variety and quantity of insects, but the southward migration of insects (in East Asia) in autumn is still poorly understood. Methods We collated daily catches of the oriental armyworm (Mythimna separata) moth from 20 searchlight traps from 2014 to 2017 in China. In order to explore the autumn migratory connectivity of M. separata in East China, we analyzed the autumn climate and simulated the autumn migration process of moths. Results The results confirmed that northward moth migration in spring and summer under the East Asian monsoon system can bring rapid population growth. However, slow southerly wind (blowing towards the north) prevailed over the major summer breeding area in North China (33°–40° N) due to a cold high-pressure system located there, and this severely disrupts the autumn ‘return’ migration of this pest. Less than 8% of moths from the summer breeding area successfully migrated back to their winter-breeding region, resulting in a sharp decline of the population abundance in autumn. As northerly winds (blowing towards the south) predominate at the eastern periphery of a high-pressure system, the westward movement of the high-pressure system leads to more northerlies over North China, increasing the numbers of moths migrating southward successfully. Therefore, an outbreak year of M. separata larvae was associated with a more westward position of the high-pressure system during the previous autumn. Conclusion These results indicate that the southward migration in autumn is crucial for sustaining pest populations of M. separata, and the position of the cold high-pressure system in September is a key environmental driver of the population size in the next year. This study indicates that the autumn migration of insects in East China is more complex than previously recognized, and that the meteorological conditions in autumn are an important driver of migratory insects’ seasonal and interannual population dynamics

T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions

Inducible Enrichment of Osa-miR1432 Confers Rice Bacterial Blight Resistance through Suppressing OsCaML2

MicroRNAs (miRNAs) handle immune response to pathogens by adjusting the function of target genes in plants. However, the experimentally documented miRNA/target modules implicated in the interplay between rice and Xanthomonas oryzae pv. oryzae (Xoo) are still in the early stages. Herein, the expression of osa-miR1432 was induced in resistant genotype IRBB5, but not susceptible genotype IR24, under Xoo strain PXO86 attack. Overexpressed osa-miR1432 heightened rice disease resistance to Xoo, indicated by enhancive enrichment of defense marker genes, raised reactive oxygen species (ROS) levels, repressed bacterial growth and shortened leaf lesion length, whilst the disruptive accumulation of osa-miR1432 accelerated rice susceptibility to Xoo infection. Noticeably, OsCaML2 (LOC_Os03g59770) was experimentally confirmed as a target gene of osa-miR1432, and the overexpressing OsCaML2 transgenic plants exhibited compromised resistance to Xoo infestation. Our results indicate that osa-miR1432 and OsCaML2 were differently responsive to Xoo invasion at the transcriptional level and fine-tune rice resistance to Xoo infection, which may be referable in resistance gene discovery and valuable in the pursuit of improving Xoo resistance in rice breeding

Integrating long noncoding RNAs and mRNAs expression profiles of response to Plasmodiophora brassicae infection in Pakchoi (Brassica campestris ssp. chinensis Makino).

The biotrophic protist Plasmodiophora brassicae causes serious damage to Brassicaceae crops grown worldwide. However, the molecular mechanism of the Brassica rapa response remains has not been determined. Long noncoding RNA and mRNA expression profiles in response to Plasmodiophora brassicae infection were investigated using RNA-seq on the Chinese cabbage inbred line C22 infected with P. brassicae. Approximately 5,193 mRNAs were significantly differentially expressed, among which 1,345 were upregulated and 3,848 were downregulated. The GO enrichment analysis shows that most of these mRNAs are related to the defense response. Meanwhile, 114 significantly differentially expressed lncRNAs were identified, including 31 upregulated and 83 downregulated. Furthermore, a total of 2,344 interaction relationships were detected between 1,725 mRNAs and 103 lncRNAs with a correlation coefficient greater than 0.8. We also found 15 P. brassicaerelated mRNAs and 16 lncRNA interactions within the correlation network. The functional annotation showed that 15 mRNAs belong to defense response proteins (66.67%), protein phosphorylation (13.33%), root hair cell differentiation (13.33%) and regulation of salicylic acid biosynthetic process (6.67%). KEGG annotation showed that the vast majority of these genes are involved in the biosynthesis of secondary metabolism pathways and plant-pathogen interactions. These results provide a new perspective on lncRNA-mRNA network function and help to elucidate the molecular mechanism of P. brassicae infection

Systemic rapamycin alone may not be a treatment option for malignant glioma: evidence from an in vivo study

The mammalian target of rapamycin (mTOR) plays a central role in regulating the proliferation of cancer cells, and mTOR-specific inhibitors such as rapamycin analogs are considered as a promising therapy for malignant glioma. In this study, we investigated the possibility of using mTOR inhibitors to treat gliomas. We used a molecular marker, phosphorylation of S6 protein, to monitor biological effects of mTOR inhibitors within xenografts. Phosphorylation was decreased more in U87MG glioma after treatment with high doses of rapamycin or its analog, torisel (10 mg/kg or 25 mg/kg), but only slightly after a low dose of rapamycin (3 mg/kg). This effect correlated with enhanced survival of rats after weekly peritoneal injections of both drugs at the highest two doses but not at the low dose. High doses of both drugs caused weight loss in rats. Clinical trial data indicates that low doses of Torisel (<3 mg/kg) were not efficacious in recurrent GBM. It is concluded that systemic administration of rapamycin analogues may not be a treatment option for patients with malignant glioma due to the intolerability of high doses that might otherwise be effective. The present study underscores the need for better pre-clinical evaluation of drugs with respect to therapeutic window.Depto. de Estadística e Investigación OperativaFac. de FarmaciaTRUEpu

<i>OsRCI-1</i>-Mediated GLVs Enhance Rice Resistance to Brown Planthoppers

Green leaf volatiles (GLVs) play pivotal roles in plant anti-herbivore defense. This study investigated whether the rice 13-lipoxygense gene OsRCI-1 is involved in GLV production and plant defense in rice. The overexpression of OsRCI-1 (oeRCI lines) in rice resulted in increased wound-induced levels of two prominent GLVs, cis-3-hexen-1-ol and cis-3-hexenal. In a previous study, we found that the overexpression of OsRCI-1 reduced the colonization by the rice brown planthopper (BPH, Nilaparvata lugens) but increased the attractiveness to the egg parasitoid Anagrus nilaparvatae compared to wild-type (WT) plants. This study found that when cis-3-hexen-1-ol, but not cis-3-hexenal, was added to WT plants, it could change the BPH’s colonization preference, i.e., more BPHs preferred to colonize the oeRCI lines. The exogenous application of cis-3-hexen-1-ol or cis-3-hexenal to BPH-infested WT plants could weaken or overturn the preference of A. nilaparvatae for oeRCI lines. However, field experiments revealed that only cis-3-hexenal was attractive to the parasitoid and increased the parasitism rates of BPH eggs. These results indicate that OsRCI-1 is involved in rice GLV production and therefore modulates both direct and indirect defense in rice