Multifunctional magnetic iron oxide nanoparticles: diverse synthetic approaches, surface modifications, cytotoxicity towards biomedical and industrial applications

Magnetic iron oxide nanoparticles (MIONPs) play a major role in the emerging fields of nanotechnology to facilitate rapid advancements in biomedical and industrial platforms. The superparamagnetic properties of MIONPs and their environment friendly synthetic methods with well-defined particle size have become indispensable to obtain their full potential in a variety of applications ranging from cellular to diverse areas of biomedical science. Thus, the broadened scope and need for MIONPs in their demanding fields of applications required to be highlighted for a comprehensive understanding of their state-of-the-art. Many synthetic methods, however, do not entirely abolish their undesired cytotoxic effects caused by free radical production and high iron dosage. In addition, the agglomeration of MIONPs has also been a major problem. To alleviate these issues, suitable surface modification strategies adaptive to MIONPs has been suggested not only for the effective cytotoxicity control but also to minimize their agglomeration. The surface modification using inorganic and organic polymeric materials would represent an efficient strategy to utilize the diagnostic and therapeutic potentials of MIONPs in various human diseases including cancer. This review article elaborates the structural and magnetic properties of MIONPs, specifically magnetite, maghemite and hematite, followed by the important synthetic methods that can be exploited for biomedical approaches. The in vivo cytotoxic effects and the possible surface modifications employed to eliminate the cytotoxicity thereby enhancing the nanoparticle efficacy are also critically discussed. The roles and applications of surface modified MIONPs in medical and industrial platforms have been described for the benefits of global well-being.This work was supported by Department of Science and Technology Nano‑ mission, Government of India [Grant No. DST/NM/NB-2018/10(G)], Science and Engineering Research Board, Department of Science and Technology, India [Grant No. YSS/2014/00026] and University Grants Commission, India [Grant No. F. 4-5(24-FRP)/2013(BSR)]. This article is a result of the project NORTE-010145-FEDER-000012, supported by Norte Portugal Regional Operational Pro‑ gramme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was also fnanced by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).info:eu-repo/semantics/publishedVersio

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions

Short-term desalination of Pulicat lagoon (Southeast India) due to the 2015 extreme flood event: insights from Land-Ocean Interactions in Coastal Zone (LOICZ) models

Abstract Introduction We investigated the magnitude and duration of desalination of Pulicat—a coastal lagoon ecosystem connected to the Bay of Bengal on the South-eastern coast of India—during the 2015 South India flood event which was a period of high-magnitude precipitation and riverine flooding. Methods We estimated freshwater runoff into the lagoon using flow accumulation models for a period of 55 days (November 1 to December 25, 2015) using daily gridded precipitation data from the Global Precipitation Measurement and a digital elevation model. Using the estimates of freshwater runoff, direct precipitation and observed salinities, we simulated water and salinity fluxes of the lagoon using the Land-Ocean Interactions in the Coastal Zone model. Further, we also used Monte Carlo simulation to estimate the uncertainty in system salinity, the residual salinity at the boundary and the freshwater residence times in the lagoon. Results We estimated that a high volume (~ 760 × 106 m3) of relatively low salinity waters (residual salinity = 23.47 psu) had been exported from the lagoon to the Bay of Bengal during the period which is likely to have caused a strong dip in the daily salinity profile of the coastal sea. We contend that the lagoon experienced ~ 40% desalination due to the 2015 event with a freshwater residence time of 18.5 days. Conclusions The study highlighted the short-term, high-magnitude desalination undergone by Pulicat lagoon during the 2015 South India floods. Considering the high residual and exchange volumes obtained from the study, we conclude that Pulicat could be a major exporter of relatively low salinity waters to the Bay of Bengal during monsoons

Master Thesis

Web page loading time is one of the critical challenges on the Internet. This topic attracts more researchers as it largely reflects the user satisfaction. A web page resources typically consists of Hyper Text Markup Language (HTML), Cascading Style-Sheet (CSS), JavaScript (JS), media files, etc. As the complexity of the web page increases, the size of files fetched from server also increases which causes delay in transmitting, loading, parsing and rendering the web page. The web page is not rendered until HTML, CSS and JS files are loaded and parsed. Not all such files are needed to be rendered for the first page. Optimizing and loading only critical les required for the first page, can considerably reduce time taken to load the web page. After the first page is rendered, the rest of the files can be loaded and executed. In this thesis, we focus on improving the time taken for First Meaningful Paint(FMP) of website by loading the critical files initially. We used Design Science Research( DSR) methodology and created a PhantomJS application, to identify and segregate used and unused CSS for the first meaningful paint of the web page. We also analyzed script files to load only critical files required for FMP and the rest later. We evaluated our experiment by studying a case on Axis Communications AB and measured its website's performance to find if our experiment reduced FMP time. It showed improvement in time taken for FMP from 1284ms to 372.6ms. Based on the results, we suggest to web developers to separate and load the files required for FMP and load the rest of the files needed for the website later, so that the first page is rendered quickly

Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1/SIV

The Fc Array is a multiplexed assay that assesses the Fc domain characteristics of antigen-specific antibodies with the potential to evaluate up to 500 antigen specificities simultaneously. Antigen-specific antibodies are captured on antigen-conjugated beads and their functional capacity is probed via an array of Fc-binding proteins including antibody subclassing reagents, Fcγ receptors, complement proteins, and lectins. Here we present the results of the optimization and formal qualification of the Fc Array, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. Assay conditions were optimized for performance and reproducibility, and the final version of the assay was then evaluated for specificity, accuracy, precision, limits of detection and quantitation, linearity, range and robustness

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

BACKGROUND: A longitudinal study determined the breadth, kinetics, and correlations of systemic and mucosal antibody responses to SARS-CoV-2 infection. METHODS: Twenty-six unvaccinated adults with confirmed COVID-19 were followed for six months with three collections of blood, nasal secretions and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays. RESULTS: Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman's ρ=0.74, 0.66, and 0.57 respectively), RBD-specific IgG in respiratory secretions (ρ=0.52), disease severity (ρ=0.59), and age (ρ=0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ=0.42) and IgA (ρ=0.63). CONCLUSIONS: Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission

SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations

Abstract SARS-CoV-2 variants have continuously emerged in the face of effective vaccines. Reduced neutralization against variants raises questions as to whether other antibody functions are similarly compromised, or if they might compensate for lost neutralization activity. Here, the breadth and potency of antibody recognition and effector function is surveyed following either infection or vaccination. Considering pregnant women as a model cohort with higher risk of severe illness and death, we observe similar binding and functional breadth for healthy and immunologically vulnerable populations, but considerably greater functional antibody breadth and potency across variants associated with vaccination. In contrast, greater antibody functional activity targeting the endemic coronavirus OC43 is noted among convalescent individuals, illustrating a dichotomy in recognition between close and distant human coronavirus strains associated with exposure history. This analysis of antibody functions suggests the differential potential for antibody effector functions to contribute to protecting vaccinated and convalescent subjects as novel variants continue to evolve

bNAb individuals have higher HIV-specific IgG subclass diversity.

<p>(<b>A</b>) A multiplex assay was used to measure levels of HIV-specific IgG subclasses present in 6 month samples from bNAb and no-bNAb individuals to 12 different HIV antigens. Median abundance of antigen-specific IgG2, IgG3 and IgG4 (orange, yellow and purple respectively) are represented as a ratio to IgG1 calculated using median fluorescence intensities. Data are representative of 2 independent experiments. Spearman´s correlations between subclass diversity score and (<b>B</b>) neutralization breadth and (<b>C</b>) Fc polyfunctionality are shown. The score was calculated as the ratio of gp120 ConC IgG2 and IgG4 relative to IgG1 levels. bNAb individuals are shown in red and no-bNAb in blue with dotted trend lines.</p

Fc effector function early in HIV infection is higher in individuals that develop bNAbs.

<p>(<b>A</b>) Purified IgG from 13 bNAb, 10 no-bNAb and 5 HIV-negative individuals (in red, blue and grey respectively) at 6 months post-infection was tested for antibody dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular trogocytosis (ADCT) and cellular cytoxicity (ADCC) using three HIV-specific antigens gp120 ConC, gp140 C.ZA.1197MB and gp120 CAP45.G3. Significant differences between groups determined by the Mann-Whitney U test are indicated by *p<0.05; **p<0.001. (<b>B</b>) Medians and IQR of different Fc effector functions for bNAb and no-bNAb individuals against all tested antigens over 36 months of infection are indicated as cumulative Fc effector function. Data are representative of 3 independent experiments. (<b>C</b>) Each Fc function was standardized by calculating a Z-score and polyfunctionality determined by addition of the Z-scores for all functions for each individual. Bars above the x-axis indicate Fc polyfunctional individuals, while those below indicate poor Fc polyfunctionality. bNAb and no-bNAb individuals are indicated in red and blue respectively. (<b>D</b>) Spearman´s correlation coefficient for the relationship between the Fc polyfunctionality Z-score and % neutralization breadth calculated by a 44 multi-clade virus panel is shown. The dashed diagonal line indicates the trend of the relationship.</p

IgG isolated from individuals that develop bNAbs shows increased gp120-specific binding to Fc receptors and complement proteins.

<p>(<b>A</b>) Binding gp120 ConC-specific IgG isolated from bNAb (red) and no-bNAb (blue) individuals to Fc receptors and C1q measured by an antigen-specific Fc receptor multiplex array. Significant differences (calculated by Mann-Whitney U test) in binding are shown as *p<0.05; **p<0.001; ***p<0.0001. Data are representative of 2 independent experiments. (<b>B</b>) The ratio of activating FcγRIIa (either H131 or R131) to inhibitory FcγRIIb receptor binding at 6 months post infection for bNAb and no-bNAb individuals. Medians are shown and significance was calculated by the Mann-Whitney U test. (<b>C</b>) Correlations between ADCT or ADCD and binding to Fc receptors and C1q shown as MFI. Significant Spearman´s correlation coefficients are indicated. Lines indicate the trend of the correlations.</p