• 【吸毒规则:古代世界中的葡萄酒和罂粟衍生物。六。罂粟是食物和毒品的来源。】 复制标题 收藏 收藏
    DOI:10.3109/10826089709039375 复制DOI
    作者列表:Nencini P
    BACKGROUND & AIMS: :Poppies were widely used during antiquity as a source of food, therapeutics, and poisons. It is likely that the alimentary value of poppy seeds was known in the Neolithic age, and there is some evidence that the neuropsychopharmacological effects of poppy juice were exploited during the Minoan civilization in the eastern Mediterranean basin. The Minoan civilization dates the attribution to poppies of symbolic meanings connected with rites of agricultural fertility. The persistence throughout antiquity of this symbolism is testified by literary and iconographic evidence of the attribution of poppies to goddesses of fertility, such as Demeter, Aphrodite, and Ceres.
    背景与目标: :在古代,罂粟被广泛用作食物,治疗剂和毒药的来源。罂粟籽的营养价值很可能是在新石器时代就已经知道的,并且有一些证据表明,罂粟汁的神经心理药理作用是在地中海东部的米诺斯文明期间被利用的。米诺斯文明可追溯到象征意义的罂粟的归属,这些象征意义与农业生育的仪式有关。这种象征主义在整个上古时代的持久性通过文学和肖像学证据证明,罂粟归因于狄特耳特,阿芙罗狄蒂和谷神星等生育女神。
  • 【猫鼬粪便中碳氮稳定同位素的鉴别因素。】 复制标题 收藏 收藏
    DOI:10.7717/peerj.3436 复制DOI
    作者列表:Montanari S
    BACKGROUND & AIMS: :Stable isotope analysis of feces can provide a non-invasive method for tracking the dietary habits of nearly any mammalian species. While fecal samples are often collected for macroscopic and genetic study, stable isotope analysis can also be applied to expand the knowledge of species-specific dietary ecology. It is somewhat unclear how digestion changes the isotope ratios of animals' diets, so more controlled diet studies are needed. To date, most diet-to-feces controlled stable isotope experiments have been performed on herbivores, so in this study I analyzed the carbon and nitrogen stable isotope ratios in the diet and feces of the meerkat (Suricata suricatta), a small omnivorous mammal. The carbon trophic discrimination factor between diet and feces (Δ13Cfeces) is calculated to be 0.1 ± 1.5‰, which is not significantly different from zero, and in turn, not different than the dietary input. On the other hand, the nitrogen trophic discrimination factor (Δ15Nfeces) is 1.5 ± 1.1‰, which is significantly different from zero, meaning it is different than the average dietary input. Based on data generated in this experiment and a review of the published literature, carbon isotopes of feces characterize diet, while nitrogen isotope ratios of feces are consistently higher than dietary inputs, meaning a discrimination factor needs to be taken into account. The carbon and nitrogen stable isotope values of feces are an excellent snapshot of diet that can be used in concert with other analytical methods to better understand ecology, diets, and habitat use of mammals.
    背景与目标: 粪便的稳定同位素分析可为追踪几乎所有哺乳动物的饮食习惯提供一种非侵入性的方法。虽然通常收集粪便样本用于宏观和遗传研究,但稳定同位素分析也可用于扩展对物种特定的饮食生态学的了解。尚不清楚消化如何改变动物饮食的同位素比率,因此需要更严格的饮食研究。迄今为止,大多数日粮对粪便控制的稳定同位素实验都是在食草动物上进行的,因此在这项研究中,我分析了杂食性小型猫鼬(Suricata suricatta)的日粮和粪便中碳和氮的稳定同位素比。饮食与粪便之间的碳营养辨别因子(Δ13Cfeces)计算为0.1±1.5‰,与零无显着差异,反过来与饮食投入也无差异。另一方面,氮营养辨别因子(Δ15Nfeces)为1.5±1.1‰,与零显着不同,这意味着它与平均饮食投入不同。根据该实验产生的数据和对公开文献的评论,粪便的碳同位素表征饮食,而粪便的氮同位素比率始终高于饮食投入,这意味着需要考虑歧视因素。粪便的碳和氮稳定同位素值是饮食的极好快照,可以与其他分析方法结合使用,以更好地了解哺乳动物的生态,饮食和栖息地。
  • 【来源可信度和电子烟态度:对烟草传播的影响。】 复制标题 收藏 收藏
    DOI:10.1080/10410236.2017.1331190 复制DOI
    作者列表:Case KR,Lazard AJ,Mackert MS,Perry CL
    BACKGROUND & AIMS: :As there are many conflicting sources of e-cigarette information, research is needed to determine the impact of these sources on e-cigarette attitudes to inform future communication campaigns. Source credibility is important in shaping attitudes toward other health topics; however, no study has examined its role in influencing e-cigarette attitudes. Data from the 2015 Health Information National Trends Survey-FDA (HINTS-FDA) were utilized to assess differences in trust in different sources by e-cigarette user status and to investigate the associations between trust in sources and e-cigarette attitudes (n = 3,738). Differences in trust in sources were examined using weighted linear regression. Associations between trust in sources of e-cigarette health effects and attitudes toward e-cigarettes were assessed using weighted logistic regression. Overall, e-cigarette ever users reported significantly lower trust in governmental agencies as compared to never users. Trust in e-cigarette companies was negatively associated with perceived addictiveness of e-cigarettes (AOR = 0.76, 95% CI = 0.58, 1.00), while trust in doctors/pharmacists/healthcare providers was negatively associated with harm perceptions of e-cigarettes relative to conventional cigarettes (AOR = 0.72, 95% CI = 0.55, 0.95). Trust in tobacco companies and trust in e-cigarette companies were negatively associated with absolute perceived harm of e-cigarettes (AOR = 0.70, 95% CI = 0.51, 0.95; AOR = 0.60, 95% CI = 0.46, 0.79, respectively). Results from this study indicate that the associations between trust in sources of e-cigarette health effects and e-cigarette attitudes differ both by source and specific attitude assessed. Ultimately, future campaigns should incorporate messaging to discredit industry sources of information and utilize non-governmental sources to effectively influence e-cigarette attitudes.
    背景与目标: :由于电子烟信息的来源众多,因此需要进行研究以确定这些来源对电子烟态度的影响,以为未来的宣传活动提供信息。来源信誉对于塑造对其他健康主题的态度很重要;但是,没有研究检查其在影响电子烟态度中的作用。利用2015年健康信息国家趋势调查(FDA)(HINTS-FDA)的数据通过电子烟用户状态评估对不同来源的信任差异,并调查对来源的信任与电子烟态度之间的关联(n = 3,738) )。使用加权线性回归检查对来源信任的差异。使用加权逻辑回归评估对电子烟健康影响来源的信任与对电子烟态度之间的关联。总体而言,与从未使用过的用户相比,曾经使用过电子烟的用户对政府机构的信任度大大降低。对电子烟公司的信任与感知的电子烟成瘾性呈负相关(AOR = 0.76,95%CI = 0.58,1.00),而对医生/药剂师/医疗保健提供者的信任与对电子烟的危害性感知呈负相关到传统卷烟(AOR = 0.72,95%CI = 0.55,0.95)。对烟草公司的信任和对电子烟公司的信任与电子烟的绝对感知危害负相关(分别为AOR = 0.70,95%CI = 0.51,0.95; AOR = 0.60,95%CI = 0.46,0.79)。这项研究的结果表明,对电子烟健康影响来源的信任与电子烟态度之间的关联因来源和所评估的特定态度而异。最终,未来的运动应结合信息传递来抹黑行业信息来源,并利用非政府来源来有效影响电子烟的态度。
  • 【使用厌氧-好氧工艺从垃圾渗滤液中去除生物氮:通过原始渗滤液中的有机物和微生物的细胞内存储聚合物进行反硝化作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.10.063 复制DOI
    作者列表:Zhu R,Wang S,Li J,Wang K,Miao L,Ma B,Peng Y
    BACKGROUND & AIMS: :A system which combined ASBR with pulsed SBR (PSBR) was introduced to enhance COD and nitrogen removal from the real landfill leachate. ASBR was used to degrade the organics from raw leachate mainly. Three equal feeds mode was applied in PSBR operation. The results obtained from the joint operation period (157 days) show that the COD removal rate of ASBR was 83-88% under the specific loading rate of 0.43-0.62 gCOD gVSS(-1) day(-1). PSBR's operation can be divided into four phases according to the different influent NH(4)(+)-N which increased to 800-1000 mg L(-1) finally, and total nitrogen (TN) removal rate of more than 90% with the effluent TN of less than 40 mg L(-1) was obtained. PHB and glycogen can act as electron donor for endogenous denitritation orderly with the hypothetical function from DNGAOs. Consequently, the system achieved COD and TN removal rate of 89.61-96.73% and 97.03-98.87%, respectively, without any extra carbon source addition.
    背景与目标: :引入了结合了ASBR和脉冲SBR(PSBR)的系统,以提高从真实垃圾填埋场渗滤液中去除COD和氮的能力。 ASBR主要用于降解原渗滤液中的有机物。在PSBR操作中应用了三个均等进给模式。从联合运行期(157天)获得的结果表明,在比加载率为0.43-0.62 gCOD gVSS(-1)day(-1)的条件下,ASBR的COD去除率为83-88%。 PSBR的操作可根据进水NH(4)-N的不同而分为四个阶段,最终将其增加至800-1000 mg L(-1),而总氮(TN)去除率超过90%,获得的废水总氮少于40 mg L(-1)。 PHB和糖原可以按DNGAOs的假设功能有序地充当内源性反硝化的电子供体。因此,该系统在不添加任何碳源的情况下,分别实现了89.61-96.73%和97.03-98.87%的COD和TN去除率。
  • 【氮芥芥诱导白细胞趋化性的分子机制。】 复制标题 收藏 收藏
    DOI:10.1016/j.mehy.2006.04.078 复制DOI
    作者列表:Crater J,Kannan S
    BACKGROUND & AIMS: :Nitrogen mustard(s) (NM) are the primary chemotherapeutic agents (Chlorambucil, BSO) that are used in treating the B-cell chronic lymphocyte leukemia (B-CLL). It is known that NM imparts oxidative stress by inducing the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production in B-lymphocytes of B-CLL. It is likely that these nitrogen mustards can cause the oxidative stress in the peripheral blood leukocytes (PBL) of B-CLL patients. It is possible that chronic exposure of PBL to NM would induce drug resistance in B-CLL patients. However, the precise molecular mechanism(s) by which NM affect the PBL are not known at present. Here, an effort is made to present plausible mechanisms by which chronic NM exposure could lead to increased PBL chemotaxis and vascular tissue damage in B-CLL patients The clinical implication of this phenomenon is most likely the unwanted organ dysfunction in B-CLL patients. Identification of viable therapeutic targets to attenuate the PBL activation during the NM therapy would be beneficial for the clinical remission of B-CLL.
    背景与目标: :氮芥(NM)是用于治疗B细胞慢性淋巴细胞白血病(B-CLL)的主要化学治疗剂(氯丁酸苄酯,BSO)。已知NM通过诱导B-CLL的B淋巴细胞中的活性氧(ROS)和活性氮(RNS)产生而赋予氧化应激。这些氮芥可能会引起B-CLL患者外周血白细胞(PBL)的氧化应激。 PBL长期暴露于NM可能会在B-CLL患者中诱导耐药性。但是,目前尚不清楚NM影响PBL的精确分子机制。在这里,我们努力提出合理的机制,通过这种机制,慢性NM暴露可能导致B-CLL患者的PBL趋化性增加和血管组织损伤。这种现象的临床意义很可能是B-CLL患者的不良器官功能障碍。鉴定在NM疗法期间减弱PBL活化的可行的治疗靶标对于B-CLL的临床缓解将是有益的。
  • 【碳源对生物电化学系统中脱氮性能的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.11.004 复制DOI
    作者列表:Feng H,Huang B,Zou Y,Li N,Wang M,Yin J,Cong Y,Shen D
    BACKGROUND & AIMS: :In order to ascertain the effects of different carbon sources (methanol, glucose, starch and NaHCO(3)) on denitrification in BESs, the experiment was conducted in a constant current, 3.5 of chemical oxygen demand to nitrate ratio in a greenhouse. Among the four carbon sources investigated in BESs, NaHCO(3) showed the highest nitrite accumulation and the ratio of soluble microbial products to soluble chemical oxygen demand (SMP/SCOD) with a value of 3.68 ± 0.68 mg/L and 94%, respectively. And the addition of organic substrates could reduce SMP production and enhance the denitrification process. In the constant voltage experiment, it was observed that the organics could be used by microbes to generate electrons at the anode. And a maximal current value of 11.0 mA in the BESs fed with starch indicated that the complex carbon source was easier to be used by microorganisms to generate electricity than the simple carbon source.
    背景与目标: :为了确定不同碳源(甲醇,葡萄糖,淀粉和NaHCO(3))对BES中反硝化的影响,该实验在恒定电流下进行,该温室中化学需氧量与硝酸盐的比率为3.5。在BES中研究的四种碳源中,NaHCO(3)表现出最高的亚硝酸盐积累和可溶性微生物产物与可溶性化学需氧量(SMP / SCOD)的比率,分别为3.68±0.68 mg / L和94% 。并且添加有机底物可以减少SMP的产生并增强反硝化过程。在恒压实验中,观察到微生物可以将有机物用于在阳极产生电子。淀粉喂养的BES中的最大电流值为11.0 mA,这表明与简单碳源相比,微生物更容易使用复杂的碳源发电。
  • 【接种物与底物比例,底物混合比例和接种源对草猪肥分批消化的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2013.07.051 复制DOI
    作者列表:Dechrugsa S,Kantachote D,Chaiprapat S
    BACKGROUND & AIMS: :Biochemical methane potential (BMP) assay was conducted at 35 °C to evaluate the effects of inoculum to substrate ratio (ISR) and substrate mix ratio between para-grass and pig manure co-digesting using different inocula. Rubber latex digester (RLD) inoculum showed higher methanogenic activity (41.4 mL CH4/gVS) than pig farm digester (PFD) inoculum (37.3 mL CH4/gVS). However, the maximum methane yields, occurred at the highest para-grass mix ratio (G), were 369.6, 437.6, 465.9 and 442.6 mL CH4/gTSadded for RLD inoculum, versus 332.4, 475.0, 519.5 and 521.9 mL/gTSadded for PFD inoculum at ISR 1, 2, 3, and 4, respectively. HPr, HBu and HVa appeared at higher G, corresponding to substrate's higher biodegradability. Response surface indicated that higher ISR and G had a significantly positive impact on methane yield. It suggested the use of higher ISR, i.e. 3 or 4, for BMP assay of these co-substrates. Dominant species of fermentative bacteria in each inoculum was tested by DGGE.
    背景与目标: :在35°C下进行生化甲烷潜力(BMP)分析,以评估接种物与底物比率(ISR)以及使用不同接种物共同消化副草和猪粪之间的底物混合比率的影响。橡胶乳胶消化器(RLD)接种物显示出更高的产甲烷活性(41.4 mL CH4 / gVS),高于养猪场消化器(PFD)接种物(37.3 mL CH4 / gVS)。然而,最大的草产量(发生在最高副草混合比(G)下)为RLD接种物,分别为369.6、437.6、465.9和442.6 mL CH4 / gTS,而PFD接种物为332.4、475.0、519.5和521.9 mL / gTS分别位于ISR 1、2、3和4。 HPr,HBu和HVa以较高的G出现,这对应于底物的较高的生物降解性。响应面表明,较高的ISR和G对甲烷产量具有明显的积极影响。它建议使用较高的ISR(即3或4)进行这些共底物的BMP测定。用DGGE检测每个接种物中的发酵菌的主要种类。
  • 【尿布中粪便的存在是使用节肢动物发育率估算死后间隔的潜在错误来源。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Goff ML,Charbonneau S,Sullivan W
    BACKGROUND & AIMS: :Second instar larvae of the fly Chrysomya megacephala (Diptera, Calliphoridae) were recovered from the diapers of a 16-month-old child abandoned by her mother on Oahu, Hawaii. The development of these larvae indicated a minimum period of 23.5 h of exposure prior to discovery of the child. Larvae of this species of fly are not normally associated with living tissues in Hawaii, but rather with feces and remains during the early stages of decomposition. Had the child in this case died and data not been provided detailing the site of infestation, the postmortem interval estimated would have been significantly longer than was actually the case, because of the development of the larvae inside the diapers of the living child. The need for caution in cases involving deaths of infants, the elderly, and individuals not capable of caring for themselves is stressed.
    背景与目标: :蝇蝇(Chrysomya megacephala,Diptera,Calliphoridae)的第二龄幼虫是从一个被母亲遗弃在夏威夷瓦胡岛的16个月大婴儿的尿布中回收的。这些幼虫的发育表明在发现孩子之前最短的暴露时间为23.5小时。这种蝇类的幼虫通常与夏威夷的生物组织无关,而与分解初期的粪便和残骸有关。如果在这种情况下该儿童死亡,并且未提供详细的侵染地点的数据,则估计的死后间隔时间将比实际情况长得多,这是因为活着的儿童尿布内的幼虫发育所致。强调了在涉及婴儿,老人和无能力照顾自己的人死亡的案件中需要谨慎的做法。
  • 【在液氮中储存超过28年后,人类精子活力和与人透明带相互作用的能力得以恢复。】 复制标题 收藏 收藏
    DOI:10.1016/j.fertnstert.2006.01.050 复制DOI
    作者列表:Clarke GN,Liu DY,Baker HW
    BACKGROUND & AIMS: :Six donor semen samples were evaluated after 28 years cryopreservation in liquid nitrogen. The results showed that the samples retained good postthaw motility recovery and normal levels of binding to the human zona pellucida and that four of the five samples tested also gave normal levels of zona-induced acrosome reaction. In conclusion, human sperm can survive very long-term storage, which is pertinent information for clinicians referring boys and young men for sperm banking before chemotherapy.
    背景与目标: :在液氮中冷冻保存28年后,评估了六个供体精液样本。结果表明,样品保持了良好的融化后运动能力,并且与人透明带的结合水平保持正常水平,所测试的五个样品中有四个也具有正常水平的带状透明质酸诱导的顶体反应。总之,人类精子可以长期保存,这对于临床医生在进行化学治疗前将男孩和年轻人推荐精子存入库具有重要意义。
  • 【IsoAid ADVANTAGE 103Pd近距离放射治疗源的蒙特卡洛剂量学表征。】 复制标题 收藏 收藏
    DOI:10.1120/jacmp.v8i2.2393 复制DOI
    作者列表:Sowards KT
    BACKGROUND & AIMS: :For roughly 25 years, 125I and 103Pd sources have been used in the treatment of various malignant diseases such as prostate cancer. Various new sources have been marketed and produced to meet the demand for new sources to use in treatment. Recently, IsoAID LLC created the ADVANTAGE 103Pd source. Various dosimetric parameters must be determined to facilitate treatment planning using this source. Theoretical determination of dosimetric characteristics, dose rate constant, radial dose function, and anisotropy function for this new source followed the American Association of Physicists in Medicine (AAPM) Task Group 43U1 recommendations. Theoretical calculations were performed in liquid water using the PTRAN Monte Carlo code version 7.44. The radial dose function of the new source was calculated in liquid water at distances up to 10.0 cm, and the anisotropy function, at distances ranging from 0.5 cm to 7.0 cm. The anisotropy factors and anisotropy constant were derived from the anisotropy function. The results in water indicate that the dose rate constant is 0.709 +/- 0.014 cGy x h-1 x U-1 and that the anisotropy constant is 0.880 +/- 0.040. The dosimetric characteristics of this new source compare favorably with those of other commercially available 103Pd sources.
    背景与目标: :大约25年以来,125I和103Pd来源已用于治疗各种恶性疾病,例如前列腺癌。已经销售和生产了各种新来源,以满足对用于治疗的新来源的需求。最近,IsoAID LLC创建了ADVANTAGE 103Pd源。必须确定各种剂量参数,以利于使用该源进行治疗计划。理论上确定该新来源的剂量特性,剂量率常数,径向剂量函数和各向异性函数的方法是遵循美国医学物理学会(AAPM)任务组43U1的建议。理论计算是在液态水中使用PTRAN蒙特卡罗代码7.44版进行的。新源的径向剂量函数是在液态水中最远10.0 cm处计算的,各向异性函数是在0.5 cm至7.0 cm范围内的距离计算的。各向异性因子和各向异性常数是从各向异性函数导出的。在水中的结果表明,剂量率常数为0.709 /-0.014 cGy x h-1 x U-1,各向异性常数为0.880 /-0.040。这种新来源的剂量学特征与其他市售103Pd来源的剂量学特征相比具有优势。
  • 【胎儿内侧中脑:多巴胺神经元移植的首选来源。】 复制标题 收藏 收藏
    DOI:10.1097/00001756-199707070-00032 复制DOI
    作者列表:Costantini LC,Lin L,Isacson O
    BACKGROUND & AIMS: Currently, fetal tissue transplantation into patients with Parkinson's disease utilizes the entire ventral mesencephalon (VM) as donor tissue. However, the resulting mixture of cell types contains a relatively low proportion of therapeutically relevant dopamine (DA) neurons. We show that differential dissection of a medial region of embryonic day 14 rat VM yields a significantly higher proportion of DA neurons (8-10%) than is found in lateral VM (2%) or whole VM (4-5%). Medial VM also contained a larger number of the specific subpopulation of DA neurons (aldehyde dehydrogenase-positive; AHD) that project to dorsolateral motor region of the striatum. Selective dissection of fetal medial VM selectively enriches DA neurons in cell preparations useful for transplantation in Parkinson's disease.

    背景与目标: 当前,将胎儿组织移植到帕金森氏病患者中是利用整个腹侧中脑(VM)作为供体组织。但是,所得的细胞类型混合物包含相对较低比例的治疗相关多巴胺(DA)神经元。我们显示,胚胎第14天大鼠VM内侧区域的差异解剖产生的DA神经元比例(8-10%)明显高于外侧VM(2%)或整个VM(4-5%)。内侧VM还包含大量投射到纹状体背外侧运动区的DA神经元的特定亚群(醛脱氢酶阳性; AHD)。胎儿内侧VM的选择性解剖在可用于帕金森氏病移植的细胞制剂中选择性富集DA神经元。

  • 【肾上腺的神经支配。二。豚鼠肾上腺的脊髓传入神经纤维的来源。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Mohamed AA,Parker TL,Coupland RE
    BACKGROUND & AIMS: :The sensory innervation of the guinea-pig adrenal medulla was studied using the fluorescent retrograde tracer Fast Blue. Labelled neurons were found in the dorsal root ganglia at segments T3-L2, the greatest contribution arising from T10 representing 15.2% of the total number of labelled cells. Labelling was ipsilateral to the site of injection of tracer into the adrenal medulla and the labelled neurons ranged in size between 6 and 36 microns. The overall size distribution fell into two groups of between 6 and 15 microns and of between 18 and 36 microns. Presumed sensory nerve endings were found in the adrenal medulla associated with chromaffin cells and vascular elements. The nerve endings were ovoid to spherical and densely packed with mitochondria. It is concluded that events occurring in the guinea-pig adrenal medulla, and possibly cortex, are monitored by sensory nerve terminals whose cell bodies lie within dorsal root ganglia. The exact distribution of the sensory nerve terminals within the adrenal gland is yet to be determined.
    背景与目标: :使用荧光逆行示踪剂Fast Blue研究了豚鼠肾上腺髓质的感觉神经。在背根神经节的T3-L2段发现了标记的神经元,T10产生的最大贡献占标记细胞总数的15.2%。标记与示踪剂注入肾上腺髓质的部位同侧,标记的神经元大小在6到36微米之间。总体尺寸分布分为6到15微米和18到36微米之间的两组。在肾上腺髓质中发现推测的感觉神经末梢与嗜铬细胞和血管元素有关。神经末梢为卵球形至球形,线粒体密集。结论是,发生在豚鼠肾上腺髓质甚至皮质中的事件是由感觉神经末梢监测的,感觉神经末梢的细胞体位于背根神经节内。肾上腺内感觉神经末梢的确切分布尚待确定。
  • 【M1变构激动剂TBPB的类似物的合成和SAR。第二部分:酰胺,磺酰胺和尿素-封端远端碱性哌啶氮的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2008.09.032 复制DOI
    作者列表:Miller NR,Daniels RN,Bridges TM,Brady AE,Conn PJ,Lindsley CW
    BACKGROUND & AIMS: :This letter describes the further synthesis and SAR, developed through an iterative analog library approach, of analogs of the highly selective M1 allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by the formation of amides, sulfonamides and ureas. Despite the large change in basicity and topology, M1 selectivity was maintained.
    背景与目标: :这封信描述了通过迭代类似物文库方法开发的高度合成的M1变构激动剂TBPB的类似物,该类似物通过形成酰胺,磺酰胺和尿素来缺失远端碱性哌啶氮,从而进一步合成并合成了SAR。尽管基本性和拓扑结构发生了很大变化,但仍保持了M1选择性。
  • 【碳源调节了光滑念珠菌生物膜细胞对氟康唑的转录反应。】 复制标题 收藏 收藏
    DOI:10.1038/s41522-020-0114-5 复制DOI
    作者列表:Alves R,Kastora SL,Gomes-Gonçalves A,Azevedo N,Rodrigues CF,Silva S,Demuyser L,Van Dijck P,Casal M,Brown AJP,Henriques M,Paiva S
    BACKGROUND & AIMS: :Candida glabrata is an important human fungal pathogen known to trigger serious infections in immune-compromised individuals. Its ability to form biofilms, which exhibit high tolerance to antifungal treatments, has been considered as an important virulence factor. However, the mechanisms involving antifungal resistance in biofilms and the impact of host niche environments on these processes are still poorly defined. In this study, we performed a whole-transcriptome analysis of C. glabrata biofilm cells exposed to different environmental conditions and constraints in order to identify the molecular pathways involved in fluconazole resistance and understand how acidic pH niches, associated with the presence of acetic acid, are able to modulate these responses. We show that fluconazole treatment induces gene expression reprogramming in a carbon source and pH-dependent manner. This is particularly relevant for a set of genes involved in DNA replication, ergosterol, and ubiquinone biosynthesis. We also provide additional evidence that the loss of mitochondrial function is associated with fluconazole resistance, independently of the growth condition. Lastly, we propose that C. glabrata Mge1, a cochaperone involved in iron metabolism and protein import into the mitochondria, is a key regulator of fluconazole susceptibility during carbon and pH adaptation by reducing the metabolic flux towards toxic sterol formation. These new findings suggest that different host microenvironments influence directly the physiology of C. glabrata, with implications on how this pathogen responds to antifungal treatment. Our analyses identify several pathways that can be targeted and will potentially prove to be useful for developing new antifungals to treat biofilm-based infections.
    背景与目标: :Candida glabrata是一种重要的人类真菌病原体,已知会在免疫受损的个体中引发严重感染。它形成生物膜的能力被证明是重要的毒力因子,该生物膜对抗真菌治疗表现出很高的耐受性。但是,涉及生物膜抗真菌性的机制以及宿主生态位环境对这些过程的影响仍知之甚少。在这项研究中,我们对暴露于不同环境条件和限制条件下的光滑小球藻生物膜细胞进行了全转录组分析,以鉴定参与氟康唑耐药性的分子途径,并了解酸性pH壁how与乙酸的存在如何相关,能够调节这些响应。我们显示氟康唑治疗诱导碳表达和pH依赖方式的基因表达重编程。这与涉及DNA复制,麦角固醇和泛醌生物合成的一组基因特别相关。我们还提供了其他证据,表明线粒体功能的丧失与氟康唑耐药性有关,而与生长条件无关。最后,我们提出,C。glabrata Mge1,参与铁代谢和线粒体蛋白质进口的陪伴酮,是通过减少代谢通向有毒固醇形成的通量来调节氟康唑在碳和pH适应性中的敏感性的关键调节剂。这些新发现表明,不同的宿主微环境直接影响了光滑念珠菌的生理,并对该病原体对抗真菌治疗的反应产生了影响。我们的分析确定了几种可靶向的途径,并可能被证明对开发新的抗真菌药以治疗基于生物膜的感染很有用。
  • 【磷酸蛋白质组学和代谢组学分析揭示了杨树对氮缺乏的性差异调节机制。】 复制标题 收藏 收藏
    DOI:10.1021/acs.jproteome.9b00600 复制DOI
    作者列表:Song H,Cai Z,Liao J,Zhang S
    BACKGROUND & AIMS: :Nitrogen (N) is a key factor impacting physiological processes in plants. Many proteins have been investigated in male and female poplars under N limitation. However, little is known about sex differences in the protein modifications and metabolites that occur in poplar leaves in response to N deficiency. In this study, as compared to N-deficient males, N-deficient females suffered greater damage from N deficiency, including chloroplast disorganization and lipid peroxidation of cellular membranes. Male poplars had greater osmotic adjustment ability than did females, allowing greater accumulation of soluble metabolites. In addition, as compared to that in N-deficient males, glycolysis was less suppressed in N-deficient females for increased enzyme activities to consume excess energy. Moreover, we found that pronounced protein phosphorylation occurred during carbon metabolism and substance transport processes in both sexes of poplar under N-limiting conditions. Sex-specific metabolites mainly included intermediates in glycolysis, amino acids, and phenylpropanoid-derived metabolites. This study provides new molecular evidence that female poplars suffer greater negative effects from N deficiency than do male poplars.
    背景与目标: 氮(N)是影响植物生理过程的关键因素。在氮限制下,已对雄性和雌性杨树中的许多蛋白质进行了研究。但是,人们对响应缺氮的杨树叶片中蛋白质修饰和代谢产物的性别差异知之甚少。在这项研究中,与缺乏N的雄性相比,缺乏N的雌性受到氮缺乏的损害更大,包括叶绿体分解和细胞膜脂质过氧化。雄性杨树的渗透调节能力比雌性更大,从而允许可溶性代谢产物积累更多。此外,与缺氮雄性相比,缺糖雌性的糖酵解作用受到抑制,因为增加的酶活性消耗了过多的能量。此外,我们发现在氮限制条件下,杨树的两性在碳代谢和物质运输过程中均发生了明显的蛋白磷酸化。性别特异性代谢物主要包括糖酵解的中间体,氨基酸和苯丙烷衍生的代谢物。这项研究提供了新的分子证据,表明雌性杨树由于氮缺乏而遭受的负面影响比雄性杨树更大。

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