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11.
Chiu-Hao Chen Sai Venkatesh Pingali Shekhar Garde Mark L. Schlossman 《Biophysical journal》2009,97(10):2794-2802
X-ray reflectivity measurements are used to determine the configuration of the C2 domain of protein kinase Cα (PKCα-C2) bound to a lipid monolayer of a 7:3 mixture of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine supported on a buffered aqueous solution. The reflectivity is analyzed in terms of the known crystallographic structure of PKCα-C2 and a slab model representation of the lipid layer. The configuration of lipid-bound PKCα-C2 is described by two angles that define its orientation, θ = 35° ± 10° and φ =210° ± 30°, and a penetration depth (=7.5 ± 2 Å) into the lipid layer. In this structure, the β-sheets of PKCα-C2 are nearly perpendicular to the lipid layer and the domain penetrates into the headgroup region of the lipid layer, but not into the tailgroup region. This configuration of PKCα-C2 determined by our x-ray reflectivity is consistent with many previous findings, particularly mutational studies, and also provides what we believe is new molecular insight into the mechanism of PKCα enzyme activation. Our analysis method, which allows us to test all possible protein orientations, shows that our data cannot be explained by a protein that is orientated parallel to the membrane, as suggested by earlier work. 相似文献
12.
Yoshimichi Hori 《Journal of plant research》1989,102(1):1-8
The adaptive significance of the emergence mode ofDioscorea japonica was studied with respect to initial plant size (seed, bulbil and tuber) and light intensity, using mathematical simulation
based on Yokoi's (1976) model.
Under 1.5% full sunlight conditions, plants emerging with only one leaf did not develop a shoot system throughout the growing
period (Hori and Oshima, 1986). Simulation indicated that, for this species of plant under poor productive conditions, the
optimal time for switch-over from the vegetative to reproductive growth phase to maximize the tuber weight at the end of the
growing period, occurred immediately following the start of autotrophic growth. By means of shoot growth patterns, small and
large size plants acquired the ability of shade tolerance and shade avoidance, respectively.
Further, the life history ofD. japonica could be expressed as a flow chart based on plant size and light intensity data. 相似文献
13.
Luo Dan Xia Zhi Li Heng Tu Danna Wang Ting Zhang Wei Peng Lu Yi Wenfu Zhang Sai Shu Junhua Xu Hui Li Yong Shi Buyun Huang Chengjiao Tang Wen Xiao Shuna Shu Xiaolan Liu Yan Zhang Yuan Guo Shan Yu Zhi Wang Baoxiang Gao Yuan Hu Qinxue Wang Hanzhong Song Xiaohui Mei Hong Zhou Xiaoqin Zheng Zhenhua 《中国病毒学》2020,35(6):861-867
In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future. 相似文献
14.
Nripendra Vikram Singh Shilpa Parashuram Jyotsana Sharma Roopa Sowjanya Potlannagari Dhinesh Babu Karuppannan Ram Krishna Pal Prakash Patil Dhananjay M. Mundewadikar Vipul R. Sangnure P.V. Parvati Sai Arun Naresh V.R. Mutha Bipin Kumar Abhishek Tripathi Sathish Kumar Peddamma Harish Kothandaraman Sailu Yellaboina Dushyant Singh Baghel Umesh K. Reddy 《Saudi Journal of Biological Sciences》2020,27(12):3514-3528
15.
Sai J. Ganesan Michael J. Feyder Ilan E. Chemmama Fei Fang Michael P. Rout Brian T. Chait Yi Shi Mary Munson Andrej Sali 《Protein science : a publication of the Protein Society》2020,29(6):1486-1501
Exocyst is an evolutionarily conserved hetero‐octameric tethering complex that plays a variety of roles in membrane trafficking, including exocytosis, endocytosis, autophagy, cell polarization, cytokinesis, pathogen invasion, and metastasis. Exocyst serves as a platform for interactions between the Rab, Rho, and Ral small GTPases, SNARE proteins, and Sec1/Munc18 regulators that coordinate spatial and temporal fidelity of membrane fusion. However, its mechanism is poorly described at the molecular level. Here, we determine the molecular architecture of the yeast exocyst complex by an integrative approach, based on a 3D density map from negative‐stain electron microscopy (EM) at ~16 Å resolution, 434 disuccinimidyl suberate and 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride cross‐links from chemical‐crosslinking mass spectrometry, and partial atomic models of the eight subunits. The integrative structure is validated by a previously determined cryo‐EM structure, cross‐links, and distances from in vivo fluorescence microscopy. Our subunit configuration is consistent with the cryo‐EM structure, except for Sec5. While not observed in the cryo‐EM map, the integrative model localizes the N‐terminal half of Sec3 near the Sec6 subunit. Limited proteolysis experiments suggest that the conformation of Exo70 is dynamic, which may have functional implications for SNARE and membrane interactions. This study illustrates how integrative modeling based on varied low‐resolution structural data can inform biologically relevant hypotheses, even in the absence of high‐resolution data. 相似文献
16.
David N. Powers Nicholas Trunfio Sai R. Velugula-Yellela Phillip Angart Anneliese Faustino Cyrus Agarabi 《Biotechnology progress》2020,36(1):e2903
Use of multivariate data analysis for the manufacturing of biologics has been increasing due to more widespread use of data-generating process analytical technologies (PAT) promoted by the US FDA. To generate a large dataset on which to apply these principles, we used an in-house model CHO DG44 cell line cultured in automated micro bioreactors alongside PAT with four commercial growth media focusing on antibody quality through N-glycosylation profiles. Using univariate analyses, we determined that different media resulted in diverse amounts of terminal galactosylation, high mannose glycoforms, and aglycosylation. Due to the amount of in-process data generated by PAT instrumentation, multivariate data analysis was necessary to ascertain which variables best modeled our glycan profile findings. Our principal component analysis revealed components that represent the development of glycoforms into terminally galacotosylated forms (G1F and G2F), and another that encompasses maturation out of high mannose glycoforms. The partial least squares model additionally incorporated metabolic values to link these processes to glycan outcomes, especially involving the consumption of glutamine. Overall, these approaches indicated a tradeoff between cellular productivity and product quality in terms of the glycosylation. This work illustrates the use of multivariate analytical approaches that can be applied to complex bioprocessing problems for identifying potential solutions. 相似文献
17.
Mario Gimona Maria Felice Brizzi Andre Boon Hwa Choo Massimo Dominici Sean M. Davidson Johannes Grillari Dirk M. Hermann Andrew F. Hill Dominique de Kleijn Ruenn Chai Lai Charles P. Lai Rebecca Lim Marta Monguió-Tortajada Maurizio Muraca Takahiro Ochiya Luis A. Ortiz Wei Seong Toh Yong Weon Yi Sai Kiang Lim 《Cytotherapy》2021,23(5):373-380
Mesenchymal stromal/stem cells (MSCs) have been widely tested against many diseases, with more than 1000 registered clinical trials worldwide. Despite many setbacks, MSCs have been approved for the treatment of graft-versus-host disease and Crohn disease. However, it is increasingly clear that MSCs exert their therapeutic functions in a paracrine manner through the secretion of small extracellular vesicles (sEVs) of 50–200 nm in diameter. Unlike living cells that can persist long-term, sEVs are non-living and non-replicative and have a transient presence in the body. Their small size also renders sEV preparations highly amenable to sterilization by filtration. Together, acellular MSC-sEV preparations are potentially safer and easier to translate into the clinic than cellular MSC products. Nevertheless, there are inherent challenges in the development of MSC-sEV drug products. MSC-sEVs are products of living cells, and living cells are sensitive to changes in the external microenvironment. Consequently, quality control metrics to measure key identity and potency features of MSC-sEV preparations have to be specified during development of MSC-sEV therapeutics. The authors have previously described quantifiable assays to define the identity of MSC-sEVs. Here the authors discuss requirements for prospective potency assays to predict the therapeutic effectiveness of the drug substance in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Although potency assays should ideally reflect the mechanism of action (MoA), this is challenging because the MoA for the reported efficacy of MSC-sEV preparations against multiple diseases of diverse underlying pathology is likely to be complex and different for each disease and difficult to fully elucidate. Nevertheless, robust potency assays could be developed by identifying the EV attribute most relevant to the intended biological activity in EV-mediated therapy and quantifying the EV attribute. Specifically, the authors highlight challenges and mitigation measures to enhance the manufacture of consistent and reproducibly potent sEV preparations, to identify and select the appropriate EV attribute for potency assays despite a complex “work-in-progress” MoA and to develop assays likely to be compliant with regulatory guidance for assay validation. 相似文献
18.
Plasmonics - This study shows development of highly sensitive and stable localized surface plasmon resonance (LSPR)-active U-bent glass and polymeric optical fiber (GOF and POF) sensor probes by a... 相似文献
19.
Zhao Ying Huang Shengnan Zhang Yun Shi Fengyan Liu Xuyao Du Sai Feng Hui 《In vitro cellular & developmental biology. Plant》2021,57(6):977-986
In Vitro Cellular & Developmental Biology - Plant - To improve the genetic transformation system for Brassica rapa L., we established a high-efficiency shoot regeneration protocol. A double... 相似文献