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11.
Joseph Laureanti Juan Brandi Elvis Offor David Engel Robert Rallo Bojana Ginovska Xavier Martinez Marc Baaden Nathan A. Baker 《Protein science : a publication of the Protein Society》2020,29(1):237-246
Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson‐Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two‐dimensional external molecular visualization software. This process has inherent limitations: visualization of three‐dimensional objects using a two‐dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol‐APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience. 相似文献
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Rebecca M. DuBois P. Jake Slavish Brandi M. Baughman Mi-Kyung Yun Ju Bao Richard J. Webby Thomas R. Webb Stephen W. White 《PLoS pathogens》2012,8(8)
Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or “snatched” from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors. 相似文献
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Miguel A. Lanaspa Laura G. Sanchez-Lozada Christina Cicerchi Nanxing Li Carlos A. Roncal-Jimenez Takuji Ishimoto Myphuong Le Gabriela E. Garcia Jeffrey B. Thomas Christopher J. Rivard Ana Andres-Hernando Brandi Hunter George Schreiner Bernardo Rodriguez-Iturbe Yuri Y. Sautin Richard J. Johnson 《PloS one》2012,7(10)
16.
G. Brandi M. Sisti G. F. Schiavano L. Salvaggio A. Albano 《Journal of applied microbiology》1996,81(4):439-444
The survival of mesophilic Aeromonas spp. in soil in the presence or absence of indigenous microflora was evaluated in a laboratory study. Two cytotoxic ( Aer. hydrophila and Aer. caviae ) and one invasive ( Aer. sobria ) clinical isolate strains were selected for this study. After contamination of sterile or unsterilized soil with the three strains of Aeromonas , the number of living cells was determined over at least 5 months. For all strains the survival curves were characterized by an initial re-growth followed by a slow inactivation of bacteria, with significant differences due to the presence of indigenous microflora. The times necessary to achieve a 95% reduction of the initial population were > 140, 113 and 62 d in sterilized soil respectively for Aer. caviae, Aer. hydrophila and Aer. sobria , while the corresponding times in unsterilized soil were 42, 38 and 11 d. All strains preserved the virulence factors for the entire period of the study. These results suggest that the soil may be an important reservoir for Aeromonas spp. and, thus, may play an important role in the epidemiology of Aeromonas -associated human infections. 相似文献
17.
G Polese A Rossi L Appendini G Brandi J H Bates R Brandolese 《Journal of applied physiology》1991,71(6):2425-2433
In ten mechanically ventilated patients, six with chronic obstructive pulmonary disease (COPD) and four with pulmonary edema, we have partitioned the total respiratory system mechanics into the lung (l) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant-flow inflation (J. Appl. Physiol. 58: 1840-1848, 1985). Intrinsic positive end-expiratory pressure (PEEPi) was present in eight patients (range 1.1-9.8 cmH2O) and was due mainly to PEEPi,L (80%), with a minor contribution from PEEPi,w (20%), on the average. The increase in respiratory elastance and resistance was determined mainly by abnormalities in lung elastance and resistance. Chest wall elastance was slightly abnormal (7.3 +/- 2.2 cmH2O/l), and chest wall resistance contributed only 10%, on the average, to the total. The work performed by the ventilator to inflate the lung (WL) averaged 2.04 +/- 0.59 and 1.25 +/- 0.21 J/l in COPD and pulmonary edema patients, respectively, whereas Ww was approximately 0.4 J/l in both groups, i.e., close to normal values. We conclude that, in mechanically ventilated patients, abnormalities in total respiratory system mechanics essentially reflect alterations in lung mechanics. However, abnormalities in chest wall mechanics can be relevant in some COPD patients with a high degree of pulmonary hyperinflation. 相似文献
18.
K B Alves C M Brandi J C Souza-Pinto J A Guimar?es 《The International journal of biochemistry》1984,16(12):1295-1300
An aminopeptidase from human urine (HUA) able to hydrolyze L-aminoacyl-2-naphthylamides, L-Leu-p-nitroanilide and to convert both MLBK and LBK to BK has been further purified and characterized. The preparation now obtained showed a 3-fold higher specific activity than the previously described one and a single active protein band in 7% polyacrylamide gel electrophoresis accounting for 86% of total protein. Kinetic constants for this kinin-converting enzyme were determined using L-aminoacyl-2-naphthylamides, L-Leu-p-nitroanilide and LBK. The Km values for different naphthylamides were in the 10(-5) M range while that for L-Leu-p-nitroanilide was 3.6 X 10(-4) M. With LBK as substrate the aminopeptidase activity showed the highest catalytic efficiency in spite of a Km in the mM range. The enzyme was poorly inhibited by -SH and -S-S- group reagents. Some L-aminoacids, as well as mono- and diamines, indomethacin, puromycin and bestatin were equipotent competitive inhibitors of both arylamidase and aminopeptidase activities. Results obtained in this paper are compatible with our conclusion that human urine, unlike other enzyme sources, contains only one aminopeptidase, and that this enzyme displays both arylamidase and kinin-converting activities. The enzyme's action may be important in the metabolism of kinins, yielding peptides which could interact with both B-1 and B-2 kinin receptors in the kidney. 相似文献
19.
Piccoli-Valle Roberta Hilsdorf Brandi Igor Viana Silva Daison Olzany Vieira Passos Frederico José 《World journal of microbiology & biotechnology》2001,17(5):433-437
Penicillium griseoroseum cultured in the presence of sucrose and yeast extract produces pectin lyase (EC 4.2.2.10) (PL) in the absence of its natural inducer pectin. This fungus was cultured in a fermenter at an aeration rate of 0.5 l/min for the first 25 h and 1.0 l/min for the remainder of the culture period, and at a stirring rate of 200 rev/min for the entire culture period. Fungal spores were inoculated directly into the fermenter at a final concentration of 5 × 104 spores/ml. The fungus was cultured in minimal medium supplemented with powdered dehydrated sugar cane juice, producing PL without added yeast extract. Maximum PL activity (0.067 IU/ml) was obtained after 65 h in batch culture. Pellet morphology of the mycelia made it possible to carry out three cycles of repeated batch culture. The same medium was used for renewal as for the single batch culture. The initial cycle was 53 h, after which approximately 0.103 IU/ml of PL was obtained. After this period, the medium was renewed and fermentation continued for two more cycles, which lasted approximately 20 h. Activity of PL obtained in the second cycle was approximately 0.118 IU/ml and in the third, approximately 0.109 IU/ml. 相似文献
20.
Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders. 相似文献