Biochemical Phenomena

生化现象
  • 文章类型: Journal Article
    我们通过在具有质量作用动力学的化学反应网络框架中消除或添加中间复合物来解决还原网络与扩展网络中的几个问题。在这种情况下,我们澄清并扩展了有关多平稳性的文献中的进展,主要来自Feliu和Wiuf(JRSocInterface10:20130484,2013),Sadeghimanesh和Feliu(公牛数学生物81:2428-2462,2019),PérezMillán和Dickenstein(SIAMJApplDynSyst17(2):1650-1682,2018),Dickenstein等人。(公牛数学生物81:1527-1581,2019)。我们建立了关于MESSI系统的一般结果,我们用它来计算重要生化网络的多平稳性电路。
    We address several questions in reduced versus extended networks via the elimination or addition of intermediate complexes in the framework of chemical reaction networks with mass-action kinetics. We clarify and extend advances in the literature concerning multistationarity in this context, mainly from Feliu and Wiuf (J R Soc Interface 10:20130484, 2013), Sadeghimanesh and Feliu (Bull Math Biol 81:2428-2462, 2019), Pérez Millán and Dickenstein (SIAM J Appl Dyn Syst 17(2):1650-1682, 2018), Dickenstein et al. (Bull Math Biol 81:1527-1581, 2019). We establish general results about MESSI systems, which we use to compute the circuits of multistationarity for significant biochemical networks.
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  • 文章类型: Journal Article
    术语“生物分子缩合物”用于描述真核细胞中的无膜区室,积累蛋白质和核酸。作为液-液相分离(LLPS)的结果,形成生物分子缩合物。通常,它们表现出液体状液滴或凝胶状聚集体的特性;然而,其中一些可能看起来结构更复杂,组织更有序。无膜微区室参与细胞质和细胞核的不同过程,其中核糖体生物发生,基因表达的调节,细胞信号,和应激反应。凝析油的性质和结构可能是高度动态的,并受到各种内部和外部因素的影响,例如,成分的浓度和相互作用,溶液温度,pH值,渗透压,等。在这次审查中,我们讨论了各种生物分子缩合物及其在活细胞中的功能,描述它们的结构变体,突出组成蛋白质和核酸的结构域和一级序列组织。最后,我们描述了表征结构的方法的当前进展,属性,形态学,生物分子缩合物的体外和体内动力学。
    The term \"biomolecular condensates\" is used to describe membraneless compartments in eukaryotic cells, accumulating proteins and nucleic acids. Biomolecular condensates are formed as a result of liquid-liquid phase separation (LLPS). Often, they demonstrate properties of liquid-like droplets or gel-like aggregates; however, some of them may appear to have a more complex structure and high-order organization. Membraneless microcompartments are involved in diverse processes both in cytoplasm and in nucleus, among them ribosome biogenesis, regulation of gene expression, cell signaling, and stress response. Condensates properties and structure could be highly dynamic and are affected by various internal and external factors, e.g., concentration and interactions of components, solution temperature, pH, osmolarity, etc. In this review, we discuss variety of biomolecular condensates and their functions in live cells, describe their structure variants, highlight domain and primary sequence organization of the constituent proteins and nucleic acids. Finally, we describe current advances in methods that characterize structure, properties, morphology, and dynamics of biomolecular condensates in vitro and in vivo.
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  • 文章类型: Journal Article
    微生物在各种各样的环境中生长,必须平衡生长和抗逆性。尽管这种权衡取舍普遍存在,对它们在非稳定环境中的作用的理解是有限的。在这项研究中,我们介绍了一个“增长债务”的数学模型,“微生物最初迅速生长的地方,稍后支付较慢的增长或死亡率升高。我们首先将我们的模型与经典的恒化器实验进行比较,验证我们提出的动力学并量化大肠杆菌的抗应激动力学。将恒化器理论扩展到包括连续稀释培养物,我们推导了“债务人”微生物持续存在的相图。我们发现,如果“付款”增加死亡率,债务人不能与非债务人共存,但如果降低酶的亲和力,则可以共存。令人惊讶的是,微弱的噪声大大扩展了电阻元件的持久性,与抗生素耐药性管理有关。我们的微生物债务理论,广泛适用于许多环境,弥合恒化器和系列稀释系统之间的差距。
    Microbes grow in a wide variety of environments and must balance growth and stress resistance. Despite the prevalence of such trade-offs, understanding of their role in nonsteady environments is limited. In this study, we introduce a mathematical model of \"growth debt,\" where microbes grow rapidly initially, paying later with slower growth or heightened mortality. We first compare our model to a classical chemostat experiment, validating our proposed dynamics and quantifying Escherichia coli\'s stress resistance dynamics. Extending the chemostat theory to include serial-dilution cultures, we derive phase diagrams for the persistence of \"debtor\" microbes. We find that debtors cannot coexist with nondebtors if \"payment\" is increased mortality but can coexist if it lowers enzyme affinity. Surprisingly, weak noise considerably extends the persistence of resistance elements, pertinent for antibiotic resistance management. Our microbial debt theory, broadly applicable across many environments, bridges the gap between chemostat and serial dilution systems.
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  • 文章类型: Journal Article
    这项横断面研究调查了患者在2019年至2022年间启动精神疾病远程医疗之前进行面对面访问的频率。
    This cross-sectional study examines how often patients had an in-person visit before initiating telemedicine for mental illness between 2019 and 2022.
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  • 文章类型: Journal Article
    通过生物分子缩合形成的细胞区室是细胞生物学的广泛特征。这些细胞器样组件在拥挤的细胞内环境中动态地分隔大分子。然而,产生凝聚液滴的分子间相互作用也可能产生停滞状态和潜在的病理组装,如纤维,骨料,和凝胶通过液滴成熟。蛋白质液-液相分离是一个亚稳态过程,所以成熟可能是相分离蛋白质的内在特性,在过饱和冷凝物中出现不同相或状态的成核。这里,我们描述了由从头设计的多肽驱动的相分离液滴和蛋白质纤维的形成。我们表征了体外和细菌细胞中超分子纤维的形成。我们表明,客户蛋白可以使用液滴形成构建体靶向细胞中的纤维。最后,我们探索了从头多肽的相分离和纤维形成之间的相互作用,显示液滴随着翻译后转换到很大程度上的β构象而成熟,类似于病理相分离的模型。
    Cellular compartments formed by biomolecular condensation are widespread features of cell biology. These organelle-like assemblies compartmentalize macromolecules dynamically within the crowded intracellular environment. However, the intermolecular interactions that produce condensed droplets may also create arrested states and potentially pathological assemblies such as fibers, aggregates, and gels through droplet maturation. Protein liquid-liquid phase separation is a metastable process, so maturation may be an intrinsic property of phase-separating proteins, where nucleation of different phases or states arises in supersaturated condensates. Here, we describe the formation of both phase-separated droplets and proteinaceous fibers driven by a de novo designed polypeptide. We characterize the formation of supramolecular fibers in vitro and in bacterial cells. We show that client proteins can be targeted to the fibers in cells using a droplet-forming construct. Finally, we explore the interplay between phase separation and fiber formation of the de novo polypeptide, showing that the droplets mature with a post-translational switch to largely β conformations, analogous to models of pathological phase separation.
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  • 文章类型: Journal Article
    光养Fe(II)氧化剂使用Fe(II)作为固定CO2的电子供体,从而连接Fe(II)的氧化,ATP形成,和生长直接取决于阳光的可用性。我们比较了短(10小时光照/14小时黑暗)和长(2-3天光照/2-3天黑暗)光照/黑暗周期与恒定光照条件对光养Fe(II)氧化剂氧化钴铁KoFox的影响。与亮/暗循环相比,在具有恒定光(在8.9天内氧化9mMFe(II))的设置中首先完成Fe(II)氧化,但短和长亮/暗循环均显示更快的最大Fe(II)氧化速率。在短周期和长周期中,Fe(II)氧化速率达到3.5±1.0和2.6±0.3mM/d,分别,与恒定光设置中的2.1±0.3mM/d相比。与恒定光设置相比,在短周期内最大的Fe(II)氧化明显更快。在所有三种光照条件下(从0.2-2.0×106个细胞/mL到1.1-1.4×108个细胞/mL),细胞生长达到大致相等的细胞数量,并在孵育的明暗阶段进行。SEM图像显示了不同的矿物结构,与光设置无关,57FeMössbauer光谱证实了在所有三个设置中形成了结晶不良的Fe(III)羟基氧化物(例如水铁矿)。我们的结果表明,黑暗时期对光养Fe(II)氧化剂有显着影响,并显着影响Fe(II)的氧化速率。
    Phototrophic Fe(II)-oxidizers use Fe(II) as electron donor for CO2 fixation thus linking Fe(II) oxidation, ATP formation, and growth directly to the availability of sunlight. We compared the effect of short (10 h light/14 h dark) and long (2-3 days light/2-3 days dark) light/dark cycles to constant light conditions for the phototrophic Fe(II)-oxidizer Chlorobium ferrooxidans KoFox. Fe(II) oxidation was completed first in the setup with constant light (9 mM Fe(II) oxidised within 8.9 days) compared to the light/dark cycles but both short and long light/dark cycles showed faster maximum Fe(II) oxidation rates. In the short and long cycle, Fe(II) oxidation rates reached 3.5 ± 1.0 and 2.6 ± 0.3 mM/d, respectively, compared to 2.1 ± 0.3 mM/d in the constant light setup. Maximum Fe(II) oxidation was significantly faster in the short cycle compared to the constant light setup. Cell growth reached roughly equivalent cell numbers across all three light conditions (from 0.2-2.0 × 106 cells/mL to 1.1-1.4 × 108 cells/mL) and took place in both the light and dark phases of incubation. SEM images showed different mineral structures independent of the light setup and 57 Fe Mössbauer spectroscopy confirmed the formation of poorly crystalline Fe(III) oxyhydroxides (such as ferrihydrite) in all three setups. Our results suggest that periods of darkness have a significant impact on phototrophic Fe(II)-oxidizers and significantly influence rates of Fe(II) oxidation.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    机器人手术代表了外科手术的一个里程碑,提供诸如侵入性较小的方法等优点,消除震颤,缩放运动,和3D可视化。这种深入分析探讨了机器人方法的复杂生化影响。使用气腹和陡峭的Trendelenburg定位可以降低肺顺应性和内脏灌注,同时增加高碳酸血症。然而,机器人手术通过最小化组织创伤来减少手术压力和炎症。这有助于更快的恢复,但可能会限制免疫功能。与开放手术相比,机器人程序还限制了缺血再灌注损伤和氧化损伤。它们还有助于保持天然的抗氧化剂防御和凝结。在临床环境中,机器人程序减少失血,疼痛,并发症,以及与传统程序相比的停留时间。然而,风险依然存在,包括设备故障,需要转换为开放手术和增加的成本。在肿瘤学方面,关于利润率的争论仍然存在,复发,和长期生存。先进技术的出现,如术中生物传感器,局部给药系统,以及人工智能的合并,可以进一步提高机器人手术的效率。然而,关于患者同意的伦理困境,隐私,access,和监管这种破坏性的创新需要解决。总的来说,这篇综述揭示了机器人手术的复杂生化含义,并强调了需要额外机械研究的领域。它提出了一种全面的方法,以负责任地最大限度地发挥机器人手术的潜力,以改善患者的预后。将技术技能与对生理和道德问题的仔细考虑相结合。
    Robotic surgery represents a milestone in surgical procedures, offering advantages such as less invasive methods, elimination of tremors, scaled motion, and 3D visualization. This in-depth analysis explores the complex biochemical effects of robotic methods. The use of pneumoperitoneum and steep Trendelenburg positioning can decrease pulmonary compliance and splanchnic perfusion while increasing hypercarbia. However, robotic surgery reduces surgical stress and inflammation by minimizing tissue trauma. This contributes to faster recovery but may limit immune function. Robotic procedures also limit ischemia-reperfusion injury and oxidative damage compared to open surgery. They also help preserve native antioxidant defenses and coagulation. In a clinical setting, robotic procedures reduce blood loss, pain, complications, and length of stay compared to traditional procedures. However, risks remain, including device failure, the need for conversion to open surgery and increased costs. On the oncology side, there is still debate about margins, recurrence, and long-term survival. The advent of advanced technologies, such as intraoperative biosensors, localized drug delivery systems, and the incorporation of artificial intelligence, may further improve the efficiency of robotic surgery. However, ethical dilemmas regarding patient consent, privacy, access, and regulation of this disruptive innovation need to be addressed. Overall, this review sheds light on the complex biochemical implications of robotic surgery and highlights areas that require additional mechanistic investigation. It presents a comprehensive approach to responsibly maximize the potential of robotic surgery to improve patient outcomes, integrating technical skill with careful consideration of physiological and ethical issues.
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  • 文章类型: Journal Article
    肥胖在儿科人群中发病率的增加需要注意其严重的并发症。事实证明,除了典型的,众所周知的代谢并发症,肥胖作为一种全身性疾病具有同样严重的风险,虽然不太明显,非代谢并发症,比如心血管疾病,多囊卵巢综合征,慢性肾病,哮喘,甲状腺功能异常,免疫和皮肤病,和心理健康问题。它们可以影响年轻身体的几乎所有系统,并在成年后留下印记。此外,肥胖也导致现有儿童疾病的恶化。因此,患有肥胖症的儿童可能会降低生活质量,身体上和精神上,他们的预期寿命可能会缩短。事实证明,在肥胖怀孕的女孩的情况下,肥胖的并发症也可能影响他们未出生的孩子。因此,采取一切必要的行动来防止肥胖在儿科人群中日益流行是极其重要的,以及治疗现有的肥胖并发症并在早期发现它们。总之,治疗患有全身性疾病如肥胖的儿童的医生必须采用整体治疗方法。
    The increasing incidence of obesity in the pediatric population requires attention to its serious complications. It turns out that in addition to typical, well-known metabolic complications, obesity as a systemic disease carries the risk of equally serious, although less obvious, non-metabolic complications, such as cardiovascular diseases, polycystic ovary syndrome, chronic kidney disease, asthma, thyroid dysfunction, immunologic and dermatologic conditions, and mental health problems. They can affect almost all systems of the young body and also leave their mark in adulthood. In addition, obesity also contributes to the exacerbation of existing childhood diseases. As a result, children suffering from obesity may have a reduced quality of life, both physically and mentally, and their life expectancy may be shortened. It also turns out that, in the case of obese pregnant girls, the complications of obesity may also affect their unborn children. Therefore, it is extremely important to take all necessary actions to prevent the growing epidemic of obesity in the pediatric population, as well as to treat existing complications of obesity and detect them at an early stage. In summary, physicians treating a child with a systemic disease such as obesity must adopt a holistic approach to treatment.
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  • 文章类型: Journal Article
    老狗是否可以学习新技巧的永恒问题也可以要求科学方法。可以在MayuShibata及其同事的文章“OmpR和NarL反应调节子家族的残留协同进化和突变景观”中找到一个这样的例子。在他们的研究中,作者使用一种既定的方法展示了一些新的技巧,直接耦合分析(DCA)。让我们先进入它的历史。
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