Di-μ1,1-azido-bis­[(2-{1-[2-(isopropyl­amino)ethyl­imino]eth­yl}phenolato)copper(II)]

In the centrosymmetric binuclear title complex, [Cu2(C13H19N2O)2(N3)2], the CuII atom adopts an elongated CuON4 square-based pyramidal coordination geometry, arising from the N,N′,O-tridentate ligand and two bridging end-on azide anions. The O atom is in the basal plane, one of the azide N atoms is in the apical site and the Cu⋯Cu separation is 3.2365 (3) Å. A pair of intra­molecular N—H⋯O hydrogen bonds helps to establish the mol­ecular conformation

Characterization of protective epitopes in a highly conserved Plasmodium falciparum antigenic protein containing repeats of acidic and basic residues

The delineation of putatively protective and immunogenic epitopes in vaccine candidate proteins constitutes a major research effort towards the development of an effective malaria vaccine. By virtue of its role in the formation of the immune clusters of merozoites, its location on the surface of merozoites, and its highly conserved nature both at the nucleotide sequence level and the amino acid sequence level, the antigen which contains repeats of acidic and basic residues (ABRA) of the human malaria parasite Plasmodium falciparum represents such an antigen. Based upon the predicted amino acid sequence of ABRA, we synthesized eight peptides, with six of these (AB-1 to AB-6) ranging from 12 to 18 residues covering the most hydrophilic regions of the protein, and two more peptides (AB-7 and AB-8) representing its repetitive sequences. We found that all eight constructs bound an appreciable amount of antibody in sera from a large proportion of P. falciparum malaria patients; two of these peptides (AB-1 and AB-3) also elicited a strong proliferation response in peripheral blood mononuclear cells from all 11 human subjects recovering from malaria. When used as carrier-free immunogens, six peptides induced a strong, boostable, immunoglobulin G-type antibody response in rabbits, indicating the presence of both B-cell determinants and T-helper-cell epitopes in these six constructs. These antibodies specifically cross-reacted with the parasite protein(s) in an immunoblot and in an immunofluorescence assay. In another immunoblot, rabbit antipeptide sera also recognized recombinant fragments of ABRA expressed in bacteria. More significantly, rabbit antibodies against two constructs (AB-1 and AB-5) inhibited the merozoite reinvasion of human erythrocytes in vitro up to ~90%. These results favor further studies so as to determine possible inclusion of these two constructs in a multicomponent subunit vaccine against asexual blood stages of P. falciparum

Characterization of protective epitopes in a highly conserved Plasmodium falciparum antigenic protein containing repeats of acidic and basic residues

The delineation of putatively protective and immunogenic epitopes in vaccine candidate proteins constitutes a major research effort towards the development of an effective malaria vaccine. By virtue of its role in the formation of the immune clusters of merozoites, its location on the surface of merozoites, and its highly conserved nature both at the nucleotide sequence level and the amino acid sequence level, the antigen which contains repeats of acidic and basic residues (ABRA) of the human malaria parasite Plasmodium falciparum represents such an antigen. Based upon the predicted amino acid sequence of ABRA, we synthesized eight peptides, with six of these (AB-1 to AB-6) ranging from 12 to 18 residues covering the most hydrophilic regions of the protein, and two more peptides (AB-7 and AB-8) representing its repetitive sequences. We found that all eight constructs bound an appreciable amount of antibody in sera from a large proportion of P. falciparum malaria patients; two of these peptides (AB-1 and AB-3) also elicited a strong proliferation response in peripheral blood mononuclear cells from all 11 human subjects recovering from malaria. When used as carrier-free immunogens, six peptides induced a strong, boostable, immunoglobulin G-type antibody response in rabbits, indicating the presence of both B-cell determinants and T-helper-cell epitopes in these six constructs. These antibodies specifically cross-reacted with the parasite protein(s) in an immunoblot and in an immunofluorescence assay. In another immunoblot, rabbit antipeptide sera also recognized recombinant fragments of ABRA expressed in bacteria. More significantly, rabbit antibodies against two constructs (AB-1 and AB-5) inhibited the merozoite reinvasion of human erythrocytes in vitro up to ∼90%. These results favor further studies so as to determine possible inclusion of these two constructs in a multicomponent subunit vaccine against asexual blood stages of P. falciparum

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Study of the properties of thermoset materials derived from epoxidized soybean oil and protein fillers

[EN] Novel bio-based thermoset formulations were prepared by using epoxidized soybean oil (ESBO), nadic methyl anhydride as a hardener and with different types of proteins as fillers. In the first part of the study, the effect of the protein-type (wheat gluten, soy protein, casein and ovalbumin) on cured ESBO materials was investigated. Thermal and mechanical properties were characterized by flexural tests, Shore D hardness, Charpy impact tests, Vicat softening temperature and heat deflection temperature. In addition, a study of the morphology of fractured surfaces by scanning electron microscopy was carried out. In general, the addition of protein-based fillers improved the mechanical and thermal properties. It was found that the highest increase of thermal and mechanical properties was achieved by ovalbumin. In the second part of the work, the effect of the total amount of ovalbumin filler was studied. Bio-based thermoset materials from ESBO and 15 wt % ovalbumin improved flexural modulus more than 150 % when compared to the unfilled material. Similar evolution was observed for other mechanical properties. Moreover, the brittleness of this composition was the minimum from the studied systems. A direct relationship between energy absorption capacity and morphologies of the failure surface was evidenced by SEM.This work is a part of the project IPT-310000-2010-037,"ECOTEXCOMP: Research and development of textile structures useful as reinforcement of composite materials with marked ecological character" funded by the "Ministerio de Ciencia e Innovacion", with an aid of 189540.20 euros, within the "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011" and funded by the European Union through FEDER funds, Technology Fund 2007-2013, "Operational Programme on R+D+I for and on behalf of the companies". Also, Generalitat Valenciana ACOMP/2012/087 is acknowledged for financial support.Fombuena Borrás, V.; Sánchez Nacher, L.; Samper Madrigal, MD.; Juárez Varón, D.; Balart Gimeno, RA. (2013). Study of the properties of thermoset materials derived from epoxidized soybean oil and protein fillers. Journal of the American Oil Chemists' Society. 90(3):449-457. https://doi.org/10.1007/s11746-012-2171-2S449457903Alonso MV, Oliet M, Garcia J, Rodriguez F, Echeverria J (2006) Gelation and isoconversional kinetic analysis of lignin-phenol-formaldehyde resol resins cure. Chem Eng J 122:159–166Altuna FI, Esposito LH, Ruseckaite RA, Stefani PM (2011) Thermal and mechanical properties of anhydride-cured epoxy resins with different contents of bio-based epoxidized soybean oil. J Appl Polym Sci 120:789–798Boquillon N, Fringant C (2000) Polymer networks derived from curing of epoxidised linseed oil: influence of different catalysts and anhydride hardeners. Polymer 41:8603–8613Boquillon N, Elbez G, Schonfeld U (2004) Properties of wheat straw particleboards bonded with different types of resin. J Wood Sci 50:230–235Chakrapani S, Crivello JV (1998) Synthesis and photoinitiated cationic polymerization of epoxidized castor oil and its derivatives. J Macromol Sci-Pure Appl Chem A35:1–20Chen F, Zhang JW (2009) A new approach for morphology control of poly(butylene adipate-co-terephthalate) and soy protein blends. Polymer 50:3770–3777Cuq B, Contard N, Guilbert S (1998) Proteins as agricultural polymers for packaging production. Am Assoc Cereal Chem 75:1–9Czub P (2006) Application of modified natural oils as reactive diluents for epoxy resins. Macromol Symp 242:60–64DdS Martini, Braga BA, Samios D (2009) On the curing of linseed oil epoxidized methyl esters with different cyclic dicarboxylic anhydrides. Polymer 50:2919–2925Dogan E, Kuesefoglu S (2008) Synthesis and in situ foaming of biodegradable malonic acid ESO polymers. 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Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells

Background: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Results: Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1aα, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. Conclusions: We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state

Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14