EPA,not DHA,prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.     

Effects of auditory stimuli on the lifespan of Drosophila melanogaster

It is well known that music can have calming effects on humans, other mammals and birds. Reducing environmental stress or enhancing the resistance to certain stressors has been shown to extend lifespan in several organisms. Evidence also suggests that mild temporary stress may also enhance stress resistance and ultimately slow the aging process. This study explored the possibility that music may influence the lifespan of the fruit fly Drosophila melanogaster, possibly by affecting responses to stress. Flies received either background sounds (control), or background sounds supplemented with music (experimental). The experimental group had classical music playing constantly at an average of 20 dB above background sound. The median lifespan of females receiving music was 42 days compared to the median of 45 days without music, but the difference was not significant. For males median lifespans were 42 days with music exposure, and 47 days without music and the difference was significant. These results suggest that exposure to classical music decreased the lifespan of male Drosophila. Both experimental and control populations showed age-dependent increases in mortality, indicating that music affects the normal aging process rather than showing overt toxicity. These results suggest that certain auditory stimuli may be stressful and can be used as insect management.     

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid ( 1 ) and fourteen known compounds ( 2 – 15 ) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids ( 1 – 11 ) using cultured macrophage RAW264.7 cells. The results show that compound 9 , and to a lesser degree compound 5 , significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.     

Acylation of non-specific phospholipase C4 determines its function in plant response to phosphate deficiency

Non-specific phospholipase C (NPC) is involved in plant growth, development and stress responses. To elucidate the mechanism by which NPCs mediate cellular functions, here we show that NPC4 is S-acylated at the C terminus and that acylation determines its plasma membrane (PM) association and function. The acylation of NPC4 was detected using NPC4 isolated from Arabidopsis and reconstituted in vitro. The C-terminal Cys-533 was identified as the S-acylation residue, and the mutation of Cys-533 to Ala-533 in NPC4 (NPC4^C533A) led to the loss of S-acylation and membrane association of NPC4. The knockout of NPC4 impeded the phosphate deficiency-induced decrease of the phosphosphingolipid glycosyl inositol phosphoryl ceramide (GIPC), but introducing NPC4^C533A to npc4-1 failed to complement this defect, thereby supporting the hypothesis that the non-acylated NPC4^C533A fails to hydrolyze GIPC during phosphate deprivation. Moreover, NPC4^C533A failed to complement the primary root growth in npc4-1 under stress. In addition, NPC4 in Brassica napus was S-acylated and mutation of the S-acylating cysteine residue of BnaC01.NPC4 led to the loss of S-acylation and its membrane association. Together, our results reveal that S-acylation of NPC4 in the C terminus is conserved and required for its membrane association, phosphosphingolipid hydrolysis and function in plant stress responses.     

不同性状的棉花及其杂交F1代对棉铃虫的抗性

通过连续两年的田间试验,系统、全面地研究了棉花对棉铃虫(Helicoverpa armigera)的形态抗虫作用。研究结果表明：在小区试验条件下,以百株累积卵量、百株平均幼虫量及百株平均蕾铃受害量为考察指标,红叶可使危害减轻28.1%、31.45%和36.O%;鸡脚叶可使其下降19.0%、25.4%和28.4%;窄卷苞叶使其降低25.8%、32.9%和34.0%;光叶使各指标分别降低32.7%、35.1%和37.3%。高棉酚(油腺)抗性主要表现为对幼虫的抗生作用,使幼虫量下降了45.1%,使蕾铃受害量下降了51.4%。此外,研究还表明,两种抗虫性状的抗性效果有累加作用,鸡脚叶与红叶联合作用使三项指标分别下降达48.3%、55.2%和57.9%;红叶与窄卷苞叶则使危害减轻了52.7%、58.3%和60.6%;具有光叶与较密油腺两个抗虫性状的品种受害可减轻29.9%、54.9%和58.3%。将一些具有相对性状的品种进行杂交,其F₁有不同的抗虫表现。红叶、鸡脚叶和光叶品种与其对照杂交后的F1代因在不同程度上保持了抗虫性状故能表现出抗性,而窄卷苞叶品种与其对照杂交后F1代苞叶正常,则未能表现出抗性。因小区条件限制了无蜜腺抗性的表达,无蜜腺小区未表现出明显差异。     

肾上腺髓质素对大鼠肠系膜微血管和微淋巴管的作用

应用活体显微电视录象技术,观察上腺髓质素对大鼠肠系膜微血管微淋巴管的作用及其对去甲肾上腺素,内皮素作用的是结果表明,ＡＤＭ直接扩张肠系膜各级微血管和向一淋巴管,拮抗ＮＥ和ＥＴ引起的微血效及微循环血流液态的异常改变。ＡＤＭ的上述作用可被一氧化氮生成抑制剂Ｎ＾９－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ（Ｌ－ＮＮＡ）显著抑制。     

玉米早期根系构型及其生理特性对土壤水分的响应

为了探明玉米早期根系结构及其对土壤水分的生理响应,揭示玉米幼苗的抗旱机理,以蠡玉18为材料,采用盆栽试验,设置轻度胁迫(LS)、中度胁迫(MS)、重度胁迫(SS)和正常供水(CK)4个水分处理,系统研究从播种开始持续水分处理对夏玉米苗期根系形态结构及活力、保护酶系统及生理调节物质的影响。结果表明:随着水分胁迫程度的加剧,玉米根长、根表面积、根体积和根干重等各形态指标较CK下降幅度逐渐增大,不同水分胁迫使夏玉米苗期根系结构存在差异。轻度和中度胁迫显著增加了细根(0.05—0.25 mm)根长和根表面积比例,重度水分胁迫显著降低粗根(0.50 mm)根长与根表面积比例。玉米苗期根冠比、根系活力和丙二醛(MDA)含量随水分胁迫程度的增强而上升,随着胁迫时间的延长,根冠比逐渐降低。根系可溶性蛋白含量随土壤水分含量的下降而下降,MS、SS处理较CK显著降低(P0.05)。夏玉米根系中SOD对水分胁迫较CAT、POD更敏感,轻度水分胁迫下主要依赖CAT、中度水分胁迫下主要依赖POD、重度水分胁迫下主要依赖SOD来降低氧化伤害;且重度胁迫下,随着胁迫时间的延长保护酶活性下降。苗期玉米通过增加根冠比、增强根系活力和不同保护酶活性及降低可溶性蛋白等渗透调节物质来协同减少水分胁迫的危害。     

The mitochondrial tRNA(Ala) T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese family with hearing loss

We report here the clinical, genetic, and molecular characterization of a large Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Two and 13 of 66 matrilineal relatives suffered from aminoglycoside-induced and nonsyndromic hearing loss, respectively. These matrilineal relatives exhibited a wide range of severity of hearing loss, varying from profound to normal hearing. In the absence of aminoglycosides, the age-at-onset of hearing impairment in these matrilineal relatives ranged from 13 to 50years. Furthermore, these affected matrilineal relatives shared some common features: bilateral hearing loss of high frequencies and symmetries. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified the homoplasmic 12S rRNA C1494T mutation and other 34 variants belonging to Eastern Asian haplogroup F1. Of these, the variant T5628C occurs at an extremely conserved nucleotide (A31) of tRNA(Ala). This variant converted a very conservative A-U to a G-U base-pairing at AC-stem of this tRNA. The disruption of this base-pairing in tRNAs by mtDNA mutations has been associated with several clinical abnormalities. The alteration of structure of the tRNA(Ala) by the T5628C mutation may lead to a failure in tRNA metabolism and lead to impairment of mitochondrial translation, thereby worsening mitochondrial dysfunctions, caused by the C1494T mutation. Therefore, this mtDNA mutation may influence the phenotypic manifestation of the 12S rRNA C1494T mutation in this Chinese pedigree.