28 results on '"Kovacs JM"'
Search Results
2. HIV-1 envelope trimer elicits higher neutralizing antibody responses than monomeric gp120
- Author
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Kovacs, JM, primary, Nkolola, JP, additional, Peng, H, additional, Cheung, A, additional, Perry, J, additional, Miller, CA, additional, Seaman, MS, additional, Barouch, D, additional, and Chen, B, additional more...
- Published
- 2012
- Full Text
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3. Seasonal changes in leaf chlorophyll a content and morphology in a sub-tropical mangrove forest of the Mexican Pacific
- Author
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Flores-de-Santiago, F, primary, Kovacs, JM, additional, and Flores-Verdugo, F, additional
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- 2012
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4. Mapping the condition of mangroves of the Mexican Pacific using C-band ENVISAT ASAR and Landsat optical data
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Kovacs, JM, primary, Zhang, C, additional, and Flores-Verdugo, FJ, additional
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- 2008
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5. Objective and owner-reported outcomes after modified cranial closing wedge ostectomy: a case series.
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Kovacs JM, Mazdarani P, Nielsen MBM, and Miles JE
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- Dogs, Animals, Retrospective Studies, Anterior Cruciate Ligament surgery, Stifle surgery, Tibia surgery, Patient Reported Outcome Measures, Osteotomy methods, Osteotomy veterinary, Dog Diseases surgery
- Abstract
Immediate and longer-term outcomes of a cranial closing wedge ostectomy variant for management of canine cranial cruciate ligament disease were assessed in this single-center retrospective consecutive study. Records and radiographs were retrieved and assessed by three independent observers to evaluate tibial plateau angle, anatomical-mechanical axis angle, tibial tuberosity distalization, and mechanical axis length before and after surgery. Kinetic gait analysis and owner questionnaires were used to assess clinical outcomes. Seventeen stifles from fifteen dogs were evaluated radiographically. Mean error from target tibial plateau angle was 0.4 degrees. Anatomical-mechanical axis angles reduced from mean 2.9 degrees preoperatively to mean - 0.9 degrees postoperatively. Tibial tuberosity distalization was mean 5.0% of mechanical axis length, and mean reduction in mechanical axis length was 0.1%. Increased tibial plateau angles were noted in 8/17 stifles, with a mean of 9.6 degrees at short-term follow-up. Major complications were observed in 9/17 stifles. Long term follow-up (mean 832 days) was obtained with gait analysis in 8/15 dogs and with questionnaire in 11/15. Most dogs (9/11) were weakly to moderately affected by osteoarthritis symptoms. All values for peak vertical force and vertical impulse normalized to body weight exceeded local lower reference limits for normal dogs, indicating acceptable limb use. Satisfactory immediate and long-term clinical outcomes appear to be possible with this technique, but the high incidence of shorter-term complications may caution against the technique or the fixation and management described here., (© 2023. The Author(s).) more...
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- 2024
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6. Factor H related proteins modulate complement activation on kidney cells.
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Renner B, Laskowski J, Poppelaars F, Ferreira VP, Blaine J, Antonioli AH, Hannan JP, Kovacs JM, van Kooten C, You Z, Pickering MC, Holers VM, and Thurman JM
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- Humans, Mice, Animals, Complement Activation, Complement System Proteins metabolism, Kidney metabolism, Complement Factor H genetics, Complement Factor H metabolism, Kidney Diseases
- Abstract
Complement activation at a particular location is determined by the balance of activating and inhibitory proteins. Factor H is a key regulator of the alternative pathway of complement, and genetic or acquired impairments in Factor H are associated with glomerular injury. The human Factor H-related proteins (FHRs) comprise a family of five proteins that are structurally related to Factor H. Variations in the genes or expression levels of the FHRs are also associated with glomerular disease, although the mechanisms of glomerular protection/injury are incompletely understood. To explore the role of the FHRs on complement regulation/dysregulation in the kidney, we expressed and purified recombinant murine FHRs (FHRs A, B, C and E). These four distinct FHRs contain binding regions with high amino acid sequence homology to binding regions within Factor H, but we observed different interactions of the FHRs with Factor H binding ligands, including heparin and C3d. There was differential binding of the FHRs to the resident kidney cell types (mesangial, glomerular endothelial, podocytes, and tubular epithelial). All four FHRs caused complement dysregulation on kidney cell surfaces in vitro, although the magnitude of the effect differed among the FHRs and also varied among the different kidney cells. However, only FHR E caused glomerular complement dysregulation when injected in vivo but did not exacerbate injury when injected into mice with ischemic acute kidney injury, an alternative pathway-mediated model. Thus, our experiments demonstrate that the FHRs have unique, and likely context-dependent, effects on the different cell types within the kidney., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.) more...
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- 2022
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7. Extrapolating canopy phenology information using Sentinel-2 data and the Google Earth Engine platform to identify the optimal dates for remotely sensed image acquisition of semiarid mangroves.
- Author
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Valderrama-Landeros L, Flores-Verdugo F, Rodríguez-Sobreyra R, Kovacs JM, and Flores-de-Santiago F
- Subjects
- Mexico, Ecosystem
- Abstract
Continuum monitoring of mangrove ecosystems is required to maintain and improve upon national mangrove conservation strategies. In particular, mangrove canopy assessments using remote sensing methods can be undertaken rapidly and, if freely available, optimize costs. Although such spaceborne data have been used for such purposes, their application to map mangroves at the species level has been limited by the capacity to provide continuous data. The objective of this study was to assess mangrove seasonal patterns using seven multispectral vegetation indices based on a Sentinel-2 (S2) time series (July 2018 to October 2019) to assess phenological trajectories of various semiarid mangrove classes in the Google Earth Engine platform using Fourier analysis for an area located in Western Mexico. The results indicate that the months from November through December and from May through July were critical in mangrove species discrimination using the EVI2, NDVI, and VARI series. The Random Forest classification accuracy for the S2 image was calculated at 79% during the optimal acquisition period (June 25, 2019), whereas only 55% accuracy was calculated for the non-optimal image acquired date (March 2, 2019). Although mangroves are considered evergreen forests, the phenological pattern of various mangrove canopies, based on these indices, were shown to be very similar to the surrounding land-based semiarid deciduous forest. Consequently, it is believed that the rainfall pattern is likely to be the key environmental factor driving mangrove phenology in this semiarid coastal system and thus the degree of success in mangrove remote sensing classification endeavors. Identifying the optimal dates when canopy spectral conditions are ideal in achieving mangrove species discrimination could be of utmost importance when purchasing more expensive very-high spatial resolution satellite images or collecting spatial data from UAVs., (Copyright © 2020. Published by Elsevier Ltd.) more...
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- 2021
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8. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.
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Bricault CA, Yusim K, Seaman MS, Yoon H, Theiler J, Giorgi EE, Wagh K, Theiler M, Hraber P, Macke JP, Kreider EF, Learn GH, Hahn BH, Scheid JF, Kovacs JM, Shields JL, Lavine CL, Ghantous F, Rist M, Bayne MG, Neubauer GH, McMahan K, Peng H, Chéneau C, Jones JJ, Zeng J, Ochsenbauer C, Nkolola JP, Stephenson KE, Chen B, Gnanakaran S, Bonsignori M, Williams LD, Haynes BF, Doria-Rose N, Mascola JR, Montefiori DC, Barouch DH, and Korber B more...
- Published
- 2019
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9. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.
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Bricault CA, Kovacs JM, Badamchi-Zadeh A, McKee K, Shields JL, Gunn BM, Neubauer GH, Ghantous F, Jennings J, Gillis L, Perry J, Nkolola JP, Alter G, Chen B, Stephenson KE, Doria-Rose N, Mascola JR, Seaman MS, and Barouch DH more...
- Subjects
- AIDS Vaccines immunology, Animals, Female, Guinea Pigs, HIV Antibodies metabolism, HIV-1 immunology, Immunization, Secondary, Longitudinal Studies, Vaccination, env Gene Products, Human Immunodeficiency Virus immunology, AIDS Vaccines administration & dosage, Antibodies, Neutralizing metabolism, HIV-1 classification, env Gene Products, Human Immunodeficiency Virus chemistry
- Abstract
A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here, we report the immunogenicity of longitudinal prime/boost vaccination regimens with a panel of HIV-1 envelope (Env) gp140 protein immunogens over a period of 200 weeks in guinea pigs. We assessed vaccine regimens that included a monovalent clade C gp140 (C97ZA012 [C97]), a tetravalent regimen consisting of four clade C gp140s (C97ZA012, 459C, 405C, and 939C [4C]), and a tetravalent regimen consisting of clade A, B, C, and mosaic gp140s (92UG037, PVO.4, C97ZA012, and Mosaic 3.1, respectively [ABCM]). We found that the 4C and ABCM prime/boost regimens were capable of eliciting greater magnitude and breadth of binding antibody responses targeting variable loop 2 (V2) over time than the monovalent C97-only regimen. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses. These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses. IMPORTANCE The elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive goal for the HIV-1 vaccine field. In this study, we explored the use of a long-term vaccination regimen with different immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses., (Copyright © 2018 Bricault et al.) more...
- Published
- 2018
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10. An assessment of commonly employed satellite-based remote sensors for mapping mangrove species in Mexico using an NDVI-based classification scheme.
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Valderrama-Landeros L, Flores-de-Santiago F, Kovacs JM, and Flores-Verdugo F
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- Mexico, Sensitivity and Specificity, Combretaceae growth & development, Environmental Monitoring methods, Forests, Remote Sensing Technology methods, Rhizophoraceae growth & development, Wetlands
- Abstract
Optimizing the classification accuracy of a mangrove forest is of utmost importance for conservation practitioners. Mangrove forest mapping using satellite-based remote sensing techniques is by far the most common method of classification currently used given the logistical difficulties of field endeavors in these forested wetlands. However, there is now an abundance of options from which to choose in regards to satellite sensors, which has led to substantially different estimations of mangrove forest location and extent with particular concern for degraded systems. The objective of this study was to assess the accuracy of mangrove forest classification using different remotely sensed data sources (i.e., Landsat-8, SPOT-5, Sentinel-2, and WorldView-2) for a system located along the Pacific coast of Mexico. Specifically, we examined a stressed semiarid mangrove forest which offers a variety of conditions such as dead areas, degraded stands, healthy mangroves, and very dense mangrove island formations. The results indicated that Landsat-8 (30 m per pixel) had the lowest overall accuracy at 64% and that WorldView-2 (1.6 m per pixel) had the highest at 93%. Moreover, the SPOT-5 and the Sentinel-2 classifications (10 m per pixel) were very similar having accuracies of 75 and 78%, respectively. In comparison to WorldView-2, the other sensors overestimated the extent of Laguncularia racemosa and underestimated the extent of Rhizophora mangle. When considering such type of sensors, the higher spatial resolution can be particularly important in mapping small mangrove islands that often occur in degraded mangrove systems. more...
- Published
- 2017
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11. HIV-1 ENVELOPE. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein.
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Chen J, Kovacs JM, Peng H, Rits-Volloch S, Lu J, Park D, Zablowsky E, Seaman MS, and Chen B
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- AIDS Vaccines chemistry, AIDS Vaccines genetics, Antibodies, Neutralizing immunology, Antigens chemistry, Antigens genetics, Antigens immunology, CD4 Antigens immunology, Cytoplasm immunology, Epitopes chemistry, Epitopes immunology, HIV Antibodies immunology, HIV Envelope Protein gp120 chemistry, HIV Envelope Protein gp120 genetics, HIV Envelope Protein gp160 chemistry, HIV Envelope Protein gp41 chemistry, HIV Envelope Protein gp41 genetics, HIV Infections prevention & control, HIV-1 chemistry, Humans, Protein Structure, Tertiary, Virion chemistry, Virion immunology, AIDS Vaccines immunology, HIV Envelope Protein gp120 immunology, HIV Envelope Protein gp160 immunology, HIV Envelope Protein gp41 immunology, HIV-1 immunology
- Abstract
A major goal for HIV-1 vaccine development is the production of an immunogen to mimic native, functional HIV-1 envelope trimeric spikes (Env) on the virion surface. We lack a reliable description of a native, functional trimer, however, because of inherent instability and heterogeneity in most preparations. We describe here two conformationally homogeneous Envs derived from difficult-to-neutralize primary isolates. All their non-neutralizing epitopes are fully concealed and independent of their proteolytic processing. Most broadly neutralizing antibodies (bnAbs) recognize these native trimers. Truncation of their cytoplasmic tail has little effect on membrane fusion, but it diminishes binding to trimer-specific bnAbs while exposing non-neutralizing epitopes. These results yield a more accurate antigenic picture than hitherto possible of a genuinely untriggered and functional HIV-1 Env; they can guide effective vaccine development., (Copyright © 2015, American Association for the Advancement of Science.) more...
- Published
- 2015
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12. A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component.
- Author
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Bricault CA, Kovacs JM, Nkolola JP, Yusim K, Giorgi EE, Shields JL, Perry J, Lavine CL, Cheung A, Ellingson-Strouss K, Rademeyer C, Gray GE, Williamson C, Stamatatos L, Seaman MS, Korber BT, Chen B, and Barouch DH more...
- Subjects
- AIDS Vaccines administration & dosage, Animals, Female, Guinea Pigs, Treatment Outcome, AIDS Vaccines immunology, Antibodies, Neutralizing blood, HIV Antibodies blood, HIV-1 immunology, Vaccination methods, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Unlabelled: The sequence diversity of human immunodeficiency virus type 1 (HIV-1) presents a formidable challenge to the generation of an HIV-1 vaccine. One strategy to address such sequence diversity and to improve the magnitude of neutralizing antibodies (NAbs) is to utilize multivalent mixtures of HIV-1 envelope (Env) immunogens. Here we report the generation and characterization of three novel, acute clade C HIV-1 Env gp140 trimers (459C, 405C, and 939C), each with unique antigenic properties. Among the single trimers tested, 459C elicited the most potent NAb responses in vaccinated guinea pigs. We evaluated the immunogenicity of various mixtures of clade C Env trimers and found that a quadrivalent cocktail of clade C trimers elicited a greater magnitude of NAbs against a panel of tier 1A and 1B viruses than any single clade C trimer alone, demonstrating that the mixture had an advantage over all individual components of the cocktail. These data suggest that vaccination with a mixture of clade C Env trimers represents a promising strategy to augment vaccine-elicited NAb responses., Importance: It is currently not known how to generate potent NAbs to the diverse circulating HIV-1 Envs by vaccination. One strategy to address this diversity is to utilize mixtures of different soluble HIV-1 envelope proteins. In this study, we generated and characterized three distinct, novel, acute clade C soluble trimers. We vaccinated guinea pigs with single trimers as well as mixtures of trimers, and we found that a mixture of four trimers elicited a greater magnitude of NAbs than any single trimer within the mixture. The results of this study suggest that further development of Env trimer cocktails is warranted., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.) more...
- Published
- 2015
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13. Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure.
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Kovacs JM, Noeldeke E, Ha HJ, Peng H, Rits-Volloch S, Harrison SC, and Chen B
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- Animals, CHO Cells, Cricetinae, Cricetulus, HIV-1 genetics, Humans, Protein Structure, Quaternary, env Gene Products, Human Immunodeficiency Virus genetics, HIV-1 chemistry, Models, Molecular, Protein Folding, Protein Multimerization, env Gene Products, Human Immunodeficiency Virus chemistry
- Abstract
The HIV-1 envelope spike [trimeric (gp160)3, cleaved to (gp120/gp41)3] is the mediator of viral entry and the principal target of humoral immune response to the virus. Production of a recombinant preparation that represents the functional spike poses a challenge for vaccine development, because the (gp120/gp41)3 complex is prone to dissociation. We have reported previously that stable HIV-1 gp140 trimers, the uncleaved ectodomains of (gp160)3, have nearly all of the antigenic properties expected for native viral spikes. Because of recent claims that uncleaved gp140 proteins may adopt a nonnative structure with three gp120 moieties "dangling" from a trimeric gp41 ectodomain in its postfusion conformation, we have inserted a long, flexible linker between gp120 and gp41 in our stable gp140 trimers to assess their stability and to analyze their conformation in solution. The modified trimer has biochemical and antigenic properties virtually identical to those of its unmodified counterpart. Both forms bind a single CD4 per trimer, suggesting that the trimeric conformation occludes two of the three CD4 sites even when a flexible linker has relieved the covalent constraint between gp120 and gp41. In contrast, an artificial trimer containing three gp120s flexibly tethered to a trimerization tag binds three CD4s and has antigenicity nearly identical to that of monomeric gp120. Moreover, the gp41 part of both modified and unmodified gp140 trimers has a structure very different from that of postfusion gp41. These results show that uncleaved gp140 trimers from suitable isolates have compact, native-like structures and support their use as candidate vaccine immunogens. more...
- Published
- 2014
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14. Applications of low altitude remote sensing in agriculture upon farmers' requests--a case study in northeastern Ontario, Canada.
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Zhang C, Walters D, and Kovacs JM
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- Altitude, Animals, Equipment Design, Farmers, Fertilizers, Insecta physiology, Ontario, Remote Sensing Technology instrumentation, Agriculture, Crops, Agricultural, Remote Sensing Technology methods
- Abstract
With the growth of the low altitude remote sensing (LARS) industry in recent years, their practical application in precision agriculture seems all the more possible. However, only a few scientists have reported using LARS to monitor crop conditions. Moreover, there have been concerns regarding the feasibility of such systems for producers given the issues related to the post-processing of images, technical expertise, and timely delivery of information. The purpose of this study is to showcase actual requests by farmers to monitor crop conditions in their fields using an unmanned aerial vehicle (UAV). Working in collaboration with farmers in northeastern Ontario, we use optical and near-infrared imagery to monitor fertilizer trials, conduct crop scouting and map field tile drainage. We demonstrate that LARS imagery has many practical applications. However, several obstacles remain, including the costs associated with both the LARS system and the image processing software, the extent of professional training required to operate the LARS and to process the imagery, and the influence from local weather conditions (e.g. clouds, wind) on image acquisition all need to be considered. Consequently, at present a feasible solution for producers might be the use of LARS service provided by private consultants or in collaboration with LARS scientific research teams. more...
- Published
- 2014
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15. Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer.
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Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC, Chen B, Korber B, Seaman MS, and Barouch DH
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Neutralizing metabolism, CD4 Antigens metabolism, Female, Guinea Pigs, HIV Antibodies blood, HIV Antibodies metabolism, HIV-1 genetics, Protein Binding, Recombinant Proteins genetics, Recombinant Proteins immunology, Recombinant Proteins metabolism, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus metabolism, HIV-1 immunology, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Unlabelled: The extraordinary diversity of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein poses a major challenge for the development of an HIV-1 vaccine. One strategy to circumvent this problem utilizes bioinformatically optimized mosaic antigens. However, mosaic Env proteins expressed as trimers have not been previously evaluated for their stability, antigenicity, and immunogenicity. Here, we report the production and characterization of a stable HIV-1 mosaic M gp140 Env trimer. The mosaic M trimer bound CD4 as well as multiple broadly neutralizing monoclonal antibodies, and biophysical characterization suggested substantial stability. The mosaic M trimer elicited higher neutralizing antibody (nAb) titers against clade B viruses than a previously described clade C (C97ZA.012) gp140 trimer in guinea pigs, whereas the clade C trimer elicited higher nAb titers than the mosaic M trimer against clade A and C viruses. A mixture of the clade C and mosaic M trimers elicited nAb responses that were comparable to the better component of the mixture for each virus tested. These data suggest that combinations of relatively small numbers of immunologically complementary Env trimers may improve nAb responses., Importance: The development of an HIV-1 vaccine remains a formidable challenge due to multiple circulating strains of HIV-1 worldwide. This study describes a candidate HIV-1 Env protein vaccine whose sequence has been designed by computational methods to address HIV-1 diversity. The characteristics and immunogenicity of this Env protein, both alone and mixed together with a clade C Env protein vaccine, are described., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.) more...
- Published
- 2014
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16. Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant Env trimers in HIV vaccination.
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Pejawar-Gaddy S, Kovacs JM, Barouch DH, Chen B, and Irvine DJ
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- Animals, Antigens, Viral immunology, Drug Carriers chemistry, Epitopes immunology, Immunity, Humoral, Mice, Molecular Weight, Protein Structure, Quaternary, Recombinant Proteins chemistry, Recombinant Proteins immunology, HIV immunology, Lipids chemistry, Nanocapsules chemistry, Protein Multimerization, Vaccination, env Gene Products, Human Immunodeficiency Virus chemistry, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Immunization strategies that elicit antibodies capable of neutralizing diverse virus strains will likely be an important part of a successful vaccine against HIV. However, strategies to promote robust humoral responses against the native intact HIV envelope trimer structure are lacking. We recently developed chemically cross-linked lipid nanocapsules as carriers of molecular adjuvants and encapsulated or surface-displayed antigens, which promoted follicular helper T-cell responses and elicited high-avidity, durable antibody responses to a candidate malaria antigen. To apply this system to the delivery of HIV antigens, Env gp140 trimers with terminal his-tags (gp140T-his) were anchored to the surface of lipid nanocapsules via Ni-NTA-functionalized lipids. Initial experiments revealed that the large (409 kDa), heavily glycosylated trimers were capable of extracting fluid phase lipids from the membranes of nanocapsules. Thus, liquid-ordered and/or gel-phase lipid compositions were required to stably anchor trimers to the particle membranes. Trimer-loaded nanocapsules combined with the clinically relevant adjuvant monophosphoryl lipid A primed high-titer antibody responses in mice at antigen doses ranging from 5 μg to as low as 100 ng, whereas titers dropped more than 50-fold over the same dose range when soluble trimer was mixed with a strong oil-in-water adjuvant comparator. Nanocapsule immunization also broadened the number of distinct epitopes on the HIV trimer recognized by the antibody response. These results suggest that nanocapsules displaying HIV trimers in an oriented, multivalent presentation can promote key aspects of the humoral response against Env immunogens. more...
- Published
- 2014
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17. Detection of complement activation using monoclonal antibodies against C3d.
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Thurman JM, Kulik L, Orth H, Wong M, Renner B, Sargsyan SA, Mitchell LM, Hourcade DE, Hannan JP, Kovacs JM, Coughlin B, Woodell AS, Pickering MC, Rohrer B, and Holers VM
- Subjects
- Animals, Biomarkers metabolism, Choroidal Neovascularization metabolism, Complement C3-C5 Convertases immunology, Complement C3d physiology, Epitopes immunology, Humans, Inflammation, Mice, Mice, Inbred C57BL, Protein Binding, Recombinant Proteins immunology, Spleen cytology, Surface Plasmon Resonance, Antibodies, Monoclonal, Murine-Derived immunology, Complement Activation, Complement C3d immunology
- Abstract
During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monoclonal antibodies (3d8b, 3d9a, and 3d29) that preferentially bind to the iC3b, C3dg, and C3d fragments in solution, but do not bind to intact C3 or C3b. The same 3 clones also bind to tissue-bound C3 activation fragments when injected systemically. Using mouse models of renal and ocular disease, we confirmed that, following systemic injection, the antibodies accumulated at sites of C3 fragment deposition within the glomerulus, the renal tubulointerstitium, and the posterior pole of the eye. To detect antibodies bound within the eye, we used optical imaging and observed accumulation of the antibodies within retinal lesions in a model of choroidal neovascularization (CNV). Our results demonstrate that imaging methods that use these antibodies may provide a sensitive means of detecting and monitoring complement activation-associated tissue inflammation. more...
- Published
- 2013
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18. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120.
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Kovacs JM, Nkolola JP, Peng H, Cheung A, Perry J, Miller CA, Seaman MS, Barouch DH, and Chen B
- Subjects
- Animals, Chromatography, Gel, Enzyme-Linked Immunosorbent Assay, Guinea Pigs, Humans, Neutralization Tests, Surface Plasmon Resonance, Ultracentrifugation, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV Envelope Protein gp120 immunology, HIV-1 immunology, Protein Multimerization immunology, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that suitably prepared envelope trimers have nearly all the antigenic properties expected for native viral spikes. These stable, rigorously homogenous trimers have antigenic properties markedly different from those of monomeric gp120s derived from the same sequences, and they induce potent neutralizing antibody responses for a cross-clade set of tier 1 and tier 2 viruses with titers substantially higher than those elicited by the corresponding gp120 monomers. These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development. more...
- Published
- 2012
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19. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.
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Shaw CD, Storek MJ, Young KA, Kovacs JM, Thurman JM, Holers VM, and Hannan JP
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- Amino Acid Substitution, Animals, Binding Sites, Complement C3d metabolism, Crystallography, X-Ray, Enzyme-Linked Immunosorbent Assay methods, Molecular Dynamics Simulation, Mutagenesis, Site-Directed, Mutant Proteins genetics, Mutant Proteins metabolism, Protein Binding, Complement C3d chemistry, Complement C3d genetics, Receptors, Complement 3d chemistry, Receptors, Complement 3d metabolism
- Abstract
The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is docked within the concave surface of C3d., (Copyright © 2010 Elsevier Ltd. All rights reserved.) more...
- Published
- 2010
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20. Biophysical investigations of complement receptor 2 (CD21 and CR2)-ligand interactions reveal amino acid contacts unique to each receptor-ligand pair.
- Author
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Kovacs JM, Hannan JP, Eisenmesser EZ, and Holers VM
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- Adaptive Immunity physiology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Binding Sites physiology, Complement C3d immunology, Complement C3d metabolism, Humans, Immunity, Innate physiology, Interferon-alpha immunology, Interferon-alpha metabolism, Ligands, Nuclear Magnetic Resonance, Biomolecular, Protein Binding physiology, Protein Structure, Quaternary, Receptors, Complement 3d immunology, Receptors, Complement 3d metabolism, Receptors, IgE immunology, Receptors, IgE metabolism, Complement C3d chemistry, Interferon-alpha chemistry, Receptors, Complement 3d chemistry, Receptors, IgE chemistry
- Abstract
Human complement receptor type 2 (CR2 and CD21) is a cell membrane receptor, with 15 or 16 extracellular short consensus repeats (SCRs), that promotes B lymphocyte responses and bridges innate and acquired immunity. The most distally located SCRs, SCR1-2, mediate the interaction of CR2 with its four known ligands (C3d, EBV gp350, IFNalpha, and CD23). To ascertain specific interacting residues on CR2, we utilized NMR studies wherein gp350 and IFNalpha were titrated into (15)N-labeled SCR1-2, and chemical shift changes indicative of specific inter-molecular interactions were identified. With backbone assignments made, the chemical shift changes were mapped onto the crystal structure of SCR1-2. With regard to gp350, the binding region of CR2 is primarily focused on SCR1 and the inter-SCR linker, specifically residues Asn(11), Arg(13), Ala(22), Arg(28), Ser(32), Arg(36), Lys(41), Lys(57), Tyr(64), Lys(67), Tyr(68), Arg(83), Gly(84), and Arg(89). With regard to IFNalpha, the binding is similar to the CR2-C3d interaction with specific residues being Arg(13), Tyr(16), Arg(28), Ser(42), Lys(48), Lys(50), Tyr(68), Arg(83), Gly(84), and Arg(89). We also report thermodynamic properties of each ligand-receptor pair determined using isothermal titration calorimetry. The CR2-C3d interaction was characterized as a two-mode binding interaction with K(d) values of 0.13 and 160 microm, whereas the CR2-gp350 and CR2-IFNalpha interactions were characterized as single site binding events with affinities of 0.014 and 0.035 microm, respectively. The compilation of chemical binding maps suggests specific residues on CR2 that are uniquely important in each of these three binding interactions. more...
- Published
- 2010
- Full Text
- View/download PDF
21. Evaluating the condition of a mangrove forest of the Mexican Pacific based on an estimated leaf area index mapping approach.
- Author
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Kovacs JM, King JM, Flores de Santiago F, and Flores-Verdugo F
- Subjects
- Mexico, Pacific Ocean, Rhizophoraceae growth & development, Avicennia growth & development, Environmental Monitoring methods, Geography, Plant Leaves growth & development
- Abstract
Given the alarming global rates of mangrove forest loss it is important that resource managers have access to updated information regarding both the extent and condition of their mangrove forests. Mexican mangroves in particular have been identified as experiencing an exceptional high annual rate of loss. However, conflicting studies, using remote sensing techniques, of the current state of many of these forests may be hindering all efforts to conserve and manage what remains. Focusing on one such system, the Teacapán-Agua Brava-Las Haciendas estuarine-mangrove complex of the Mexican Pacific, an attempt was made to develop a rapid method of mapping the current condition of the mangroves based on estimated LAI. Specifically, using an AccuPAR LP-80 Ceptometer, 300 indirect in situ LAI measurements were taken at various sites within the black mangrove (Avicennia germinans) dominated forests of the northern section of this system. From this sample, 225 measurements were then used to develop linear regression models based on their relationship with corresponding values derived from QuickBird very high resolution optical satellite data. Specifically, regression analyses of the in situ LAI with both the normalized difference vegetation index (NDVI) and the simple ration (SR) vegetation index revealed significant positive relationships [LAI versus NDVI (R (2) = 0.63); LAI versus SR (R (2) = 0.68)]. Moreover, using the remaining sample, further examination of standard errors and of an F test of the residual variances indicated little difference between the two models. Based on the NDVI model, a map of estimated mangrove LAI was then created. Excluding the dead mangrove areas (i.e. LAI = 0), which represented 40% of the total 30.4 km(2) of mangrove area identified in the scene, a mean estimated LAI value of 2.71 was recorded. By grouping the healthy fringe mangrove with the healthy riverine mangrove and by grouping the dwarf mangrove together with the poor condition mangrove, mean estimated LAI values of 4.66 and 2.39 were calculated, respectively. Given that the former healthy group only represents 8% of the total mangrove area examined, it is concluded that this mangrove system, considered one of the most important of the Pacific coast of the Americas, is currently experiencing a considerable state of degradation. Furthermore, based on the results of this investigation it is suggested that this approach could provide resource managers and scientists alike with a very rapid and effective method for monitoring the state of remaining mangrove forests of the Mexican Pacific and, possibly, other areas of the tropics. more...
- Published
- 2009
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22. Mapping of the C3d ligand binding site on complement receptor 2 (CR2/CD21) using nuclear magnetic resonance and chemical shift analysis.
- Author
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Kovacs JM, Hannan JP, Eisenmesser EZ, and Holers VM
- Subjects
- Binding Sites, Complement C3d genetics, Enzyme-Linked Immunosorbent Assay, Humans, Ligands, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Peptides pharmacology, Protein Binding, Protein Folding, Protein Structure, Quaternary, Receptors, Complement 3d antagonists & inhibitors, Receptors, Complement 3d genetics, Titrimetry, Complement C3d chemistry, Complement C3d metabolism, Receptors, Complement 3d chemistry, Receptors, Complement 3d metabolism
- Abstract
Complement receptor 2 (CR2, CD21) is a cell membrane protein, with 15 or 16 extracellular short consensus repeats (SCRs), that promotes B lymphocyte responses and bridges innate and acquired immunity. The most distally located SCRs (SCR1-2) mediate the interaction of CR2 with its four known ligands (C3d, Epstein-Barr virus gp350, interferon-alpha, and CD23). Inhibitory monoclonal antibodies against SCR1-2 block binding of all ligands. To develop ligand-specific inhibitors that would also assist in identifying residues unique to each receptor-ligand interaction, phage were selected from randomly generated libraries by panning with recombinant SCR1-2, followed by specific ligand-driven elution. Derived peptides were tested by competition ELISA. One peptide, C3dp1 (APQHLSSQYSRT) exhibited ligand-specific inhibition at midmicromolar IC(50). C3d was titrated into (15)N-labeled SCR1-2, which revealed chemical shift changes indicative of specific intermolecular interactions. With backbone assignments made, the chemical shift changes were mapped onto the crystal structure of SCR1-2. With regard to C3d, the binding surface includes regions of SCR1, SCR2, and the inter-SCR linker, specifically residues Arg(13), Tyr(16), Arg(28), Tyr(29), Ser(32), Thr(34), Lys(48), Asp(56), Lys(57), Tyr(68), Arg(83), Gly(84), Asn(101), Asn(105), and Ser(109). SCR1 and SCR2 demonstrated distinct binding modes. The CR2 binding surface incorporating SCR1 is inconsistent with a previous x-ray CR2-C3d co-crystal analysis but consistent with mutagenesis, x-ray neutron scattering, and inhibitory monoclonal antibody epitope mapping. Titration with C3dp1 yielded chemical shift changes (Arg(13), Tyr(16), Thr(34), Lys(48), Asp(56), Lys(57), Tyr(68), Arg(83), Gly(84), Asn(105), and Ser(109)) overlapping with C3d, indicating that C3dp1 interacts at the same CR2 site as C3d. more...
- Published
- 2009
- Full Text
- View/download PDF
23. Intrinsic amino acid side-chain hydrophilicity/hydrophobicity coefficients determined by reversed-phase high-performance liquid chromatography of model peptides: comparison with other hydrophilicity/hydrophobicity scales.
- Author
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Mant CT, Kovacs JM, Kim HM, Pollock DD, and Hodges RS
- Subjects
- Amides chemistry, Amides isolation & purification, Amino Acids chemistry, Amino Acids isolation & purification, Chromatography, High Pressure Liquid methods, Chromatography, Reverse-Phase methods, Hydrogen-Ion Concentration, Protein Conformation, Hydrophobic and Hydrophilic Interactions, Peptides chemistry, Peptides isolation & purification
- Abstract
An accurate determination of the intrinsic hydrophilicity/hydrophobicity of amino acid side-chains in peptides and proteins is fundamental in understanding many area of research, including protein folding and stability, peptide and protein function, protein-protein interactions and peptide/protein oligomerization, as well as the design of protocols for purification and characterization of peptides and proteins. Our definition of intrinsic hydrophilicity/hydrophobicity of side-chains is the maximum possible hydrophilicity/hydrophobicity of side-chains in the absence of any nearest-neighbor effects and/or any conformational effects of the polypeptide chain that prevent full expression of side-chain hydrophilicity/hydrophobicity. In this review, we have compared an experimentally derived intrinsic side-chain hydrophilicity/hydrophobicity scale generated from RP-HPLC retention behavior of de novo designed synthetic model peptides at pH 2 and pH 7 with other RP-HPLC-derived scales, as well as scales generated from classic experimental and calculation-based methods of octanol/water partitioning of Nalpha-acetyl-amino-acid amides or free energy of transfer of free amino acids. Generally poor correlation was found with previous RP-HPLC-derived scales, likely due to the random nature of the peptide mixtures in terms of varying peptide size, conformation and frequency of particular amino acids. In addition, generally poor correlation with the classical approaches served to underline the importance of the presence of a polypeptide backbone when generating intrinsic values. We have shown that the intrinsic scale determined here is in full agreement with the structural characteristics of amino acid side-chains., (Copyright 2009 Wiley Periodicals, Inc.) more...
- Published
- 2009
- Full Text
- View/download PDF
24. Requirements for prediction of peptide retention time in reversed-phase high-performance liquid chromatography: hydrophilicity/hydrophobicity of side-chains at the N- and C-termini of peptides are dramatically affected by the end-groups and location.
- Author
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Tripet B, Cepeniene D, Kovacs JM, Mant CT, Krokhin OV, and Hodges RS
- Subjects
- Amino Acid Sequence, Mass Spectrometry, Peptides chemistry, Chromatography, High Pressure Liquid methods, Peptides isolation & purification
- Abstract
The value of reversed-phase high-performance liquid chromatography (RP-HPLC) and the field of proteomics would be greatly enhanced by accurate prediction of retention times of peptides of known composition. The present study investigates the hydrophilicity/hydrophobicity of amino acid side-chains at the N- and C-termini of peptides while varying the functional end-groups at the termini. We substituted all 20 naturally occurring amino acids at the N- and C-termini of a model peptide sequence, where the functional end-groups were N(alpha)-acetyl-X- and N(alpha)-amino-X- at the N-terminus and -X-C(alpha)-carboxyl and -X-C(alpha)-amide at the C-terminus. Amino acid coefficients were subsequently derived from the RP-HPLC retention behaviour of these peptides and compared to each other as well as to coefficients determined in the centre of the peptide chain (internal coefficients). Coefficients generated from residues substituted at the C-terminus differed most (between the -X-C(alpha)-carboxyl and -X-C(alpha)-amide peptide series) for hydrophobic side-chains. A similar result was seen for the N(alpha)-acetyl-X- and N(alpha)-amino-X- peptide series, where the largest differences in coefficient values were observed for hydrophobic side-chains. Coefficients derived from substitutions at the C-terminus for hydrophobic amino acids were dramatically different compared to internal coefficients for hydrophobic side-chains, ranging from 17.1 min for Trp to 4.8 min for Cys. In contrast, coefficients derived from substitutions at the N-terminus showed relatively small differences from the internal coefficients. Subsequent prediction of peptide retention time, within an error of just 0.4 min, was achieved by a predictive algorithm using a combination of internal coefficients and coefficients for the C-terminal residues. For prediction of peptide retention time, the sum of the coefficients must include internal and terminal coefficients. more...
- Published
- 2007
- Full Text
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25. HPLC analysis and purification of peptides.
- Author
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Mant CT, Chen Y, Yan Z, Popa TV, Kovacs JM, Mills JB, Tripet BP, and Hodges RS
- Subjects
- Amino Acid Sequence, Amino Acids chemistry, Animals, Antimicrobial Cationic Peptides chemistry, Antimicrobial Cationic Peptides isolation & purification, Chromatography, High Pressure Liquid instrumentation, Chromatography, High Pressure Liquid standards, Chromatography, Ion Exchange methods, Drug Stability, Electrophoresis, Capillary methods, Hydrophobic and Hydrophilic Interactions, Molecular Biology methods, Molecular Sequence Data, Oligopeptides chemistry, Oligopeptides isolation & purification, Peptides chemistry, Peptides standards, Protein Conformation, Protein Structure, Secondary, Recombinant Proteins chemistry, Recombinant Proteins isolation & purification, Reference Standards, Temperature, Chromatography, High Pressure Liquid methods, Peptides isolation & purification
- Abstract
High-performance liquid chromatography (HPLC) has proved extremely versatile over the past 25 yr for the isolation and purification of peptides varying widely in their sources, quantity and complexity. This article covers the major modes of HPLC utilized for peptides (size-exclusion, ion-exchange, and reversed-phase), as well as demonstrating the potential of a novel mixed-mode hydrophilic interaction/cation-exchange approach developed in this laboratory. In addition to the value of these HPLC modes for peptide separations, the value of various HPLC techniques for structural characterization of peptides and proteins will be addressed, e.g., assessment of oligomerization state of peptides/proteins by size-exclusion chromatography and monitoring the hydrophilicity/hydrophobicity of amphipathic alpha-helical peptides, a vital precursor for the development of novel antimicrobial peptides. The value of capillary electrophoresis for peptide separations is also demonstrated. Preparative reversed-phase chromatography purification protocols for sample loads of up to 200 mg on analytical columns and instrumentation are introduced for both peptides and recombinant proteins. more...
- Published
- 2007
- Full Text
- View/download PDF
26. Quantitation of the nearest-neighbour effects of amino acid side-chains that restrict conformational freedom of the polypeptide chain using reversed-phase liquid chromatography of synthetic model peptides with L- and D-amino acid substitutions.
- Author
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Kovacs JM, Mant CT, Kwok SC, Osguthorpe DJ, and Hodges RS
- Subjects
- Chromatography, High Pressure Liquid, Circular Dichroism, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Stereoisomerism, Amino Acids chemistry, Oligopeptides chemistry, Oligopeptides isolation & purification, Protein Conformation
- Abstract
Side-chain backbone interactions (or "effects") between nearest neighbours may severely restrict the conformations accessible to a polypeptide chain and thus represent the first step in protein folding. We have quantified nearest-neighbour effects (i to i+1) in peptides through reversed-phase liquid chromatography (RP-HPLC) of model synthetic peptides, where L- and D-amino acids were substituted at the N-terminal end of the peptide sequence, adjacent to a L-Leu residue. These nearest-neighbour effects (expressed as the difference in retention times of L- and D-peptide diastereomers at pHs 2 and 7) were frequently dramatic, depending on the type of side-chain adjacent to the L-Leu residue, albeit such effects were independent of mobile phase conditions. No nearest-neighbour effects were observed when residue i is adjacent to a Gly residue. Calculation of minimum energy conformations of selected peptides supported the view that, whether a L- or D-amino acid is substituted adjacent to L-Leu, its orientation relative to this bulky Leu side-chain represents the most energetically favourable configuration. We believe that such energetically favourable, and different, configurations of L- and D-peptide diastereomers affect their respective interactions with a hydrophobic stationary phase, which are thus quantified by different RP-HPLC retention times. Side-chain hydrophilicity/hydrophobicity coefficients were generated in the presence of these nearest-neighbour effects and, despite the relative difference in such coefficients generated from peptides substituted with L- or D-amino acids, the relative difference in hydrophilicity/hydrophobicity between different amino acids in the L- or D-series is maintained. Overall, our results demonstrate that such nearest-neighbour effects can clearly restrict conformational space of an amino acid side-chain in a polypeptide chain. more...
- Published
- 2006
- Full Text
- View/download PDF
27. Determination of intrinsic hydrophilicity/hydrophobicity of amino acid side chains in peptides in the absence of nearest-neighbor or conformational effects.
- Author
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Kovacs JM, Mant CT, and Hodges RS
- Subjects
- Amino Acid Sequence, Amino Acids chemistry, Buffers, Chromatography, High Pressure Liquid, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Kinetics, Oligopeptides chemical synthesis, Oligopeptides isolation & purification, Salts pharmacology, Amino Acids metabolism, Oligopeptides chemistry, Oligopeptides metabolism, Protein Conformation, Protein Structure, Secondary
- Abstract
Understanding the hydrophilicity/hydrophobicity of amino acid side chains in peptides/proteins is one the most important aspects of biology. Though many hydrophilicity/hydrophobicity scales have been generated, an "intrinsic" scale has yet to be achieved. "Intrinsic" implies the maximum possible hydrophilicity/hydrophobicity of side chains in the absence of nearest-neighbor or conformational effects that would decrease the full expression of the side-chain hydrophilicity/hydrophobicity when the side chain is in a polypeptide chain. Such a scale is the fundamental starting point for determining the parameters that affect side-chain hydrophobicity and for quantifying such effects in peptides and proteins. A 10-residue peptide sequence, Ac-X-G-A-K-G-A-G-V-G-L-amide, was designed to enable the determination of the intrinsic values, where position X was substituted by all 20 naturally occurring amino acids and norvaline, norleucine, and ornithine. The coefficients were determined by reversed-phase high-performance liquid chromatography using six different mobile phase conditions involving different pH values (2, 5, and 7), ion-pairing reagents, and the presence and absence of different salts. The results show that the intrinsic hydrophilicity/hydrophobicity of amino acid side chains in peptides (proteins) is independent of pH, buffer conditions, or whether C(8) or C(18) reversed-phase columns were used for 17 side chains (Gly, Ala, Cys, Pro, Val, nVal, Leu, nLeu, Ile, Met, Tyr, Phe, Trp, Ser, Thr, Asn, and Gln) and dependent on pH and buffer conditions, including the type of salt or ion-pairing reagent for potentially charged side chains (Orn, Lys, His, Arg, Asp, and Glu)., (Copyright 2006 Wiley Periodicals, Inc.) more...
- Published
- 2006
- Full Text
- View/download PDF
28. Mapping disturbances in a mangrove forest using multi-date landsat TM imagery.
- Author
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Kovacs JM, Wang J, and Blanco-Correa M
- Subjects
- Disasters, Ecosystem, Water Movements, Conservation of Natural Resources, Environmental Monitoring methods, Spacecraft, Trees
- Abstract
To evaluate the accounts of local fishermen, Landsat TM images (1986, 1993, 1999) were examined to assess potential losses in the mangrove forests of the Teacapán-Agua Brava lagoon system, Mexico. A binary change mask derived from image differencing of a band 4/3 ratio was employed to calculate any changes within this forested wetland. The results indicate that by 1986 approximately 18% (or 86 km2) of the mangrove area under study was either dead or in poor condition. The majority of this damage had occurred in the eastern section of the Agua Brava basin, which coincides, with the reports of the elderly fishermen. Examination of aerial photographs from 1970 revealed no adverse impacts in this area and would suggest, as postulated by the fishermen and other scientists, that modifications in environmental conditions following the opening of a canal, Cuautlá canal, in 1972 may have initiated the large-scale mortality. Although these areas of impact are still developing, the results from the satellite data indicate that the majority of the more recent changes are occurring elsewhere in the system. Obvious in the 1999 satellite data, but not so in the 1993, are large areas of mangrove degradation in the northern section of the Teacapán region. In the Agua Brava basin, the more recent transformations are appearing on the western side of the basin. Since long-term records of environmental conditions are absent, it is difficult to determine why these latest changes are occurring or even if the earlier losses were the result of the canal. Potential agents of change that have recently been observed include a hurricane, a second canal, and the uncontrolled expansion of the Cuautlá canal since 1994. more...
- Published
- 2001
- Full Text
- View/download PDF
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