The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene-Based α-Aminocresols Targeting Hemozoin Inhibition and DNA Interaction

The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation of potent drug leads in the quest for therapeutic chemotypes with the potential to overcome the development of clinical resistance. Herein, we present the in vitro antiplasmodial and antiproliferative investigation of ferrocenyl α-aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and an α-aminocresol scaffold possessing antimalarial activity. The compounds pursued in the study exhibited higher toxicity towards the chemosensitive (3D7) and -resistant (Dd2) strains of the Plasmodium falciparum parasite than to the human HCC70 triple-negative breast cancer cell line. Indication of cross-resistance was absent for the compounds evaluated against the multi-resistant Dd2 strain. Structure-activity analysis revealed that the phenolic hydroxy group and rotatable σ bond between the α-carbon and NH group of the α-amino-o-cresol skeleton are crucial for the biological activity of the compounds. Spectrophotometric techniques and in silico docking simulations performed on selected derivatives suggest that the compounds show a dual mode of action involving hemozoin inhibition and DNA interaction via minor-groove binding. Lastly, compound 9 a , identified as a possible lead, exhibited preferential binding for the plasmodial DNA isolated from 3D7 P. falciparum trophozoites over the mammalian calf thymus DNA, thereby substantiating the enhanced antiplasmodial activity of the compounds. The presented research demonstrates the strategy of incorporating organometallic complexes into known biologically active organic scaffolds as a viable avenue to fashion novel multimodal compounds with potential to counter the development drug resistance.     

Highly photoemissive polymer–transition metal complexes based on poly(2‐hydroxyethyl) methacrylate

The paper presents several new polymer complexes based on poly(2‐hydroxyethyl) methacrylate (P‐HEMA) and transition metals including Y³⁺, Eu³⁺, Tb³⁺ and Dy³⁺. Red‐, green‐, blue‐ and yellow‐emitting polymer complexes with remarkable photoluminescent (PL) properties, high degree of transparency and excellent processability both in bulk and in thin film were prepared and investigated. In the case of the prepared P‐HEMA–Eu³⁺ and P‐HEMA–Tb³⁺ polymer complexes, divinylbenzene was used as a crosslinker resulting a markedly enhanced PL emission, most probably due to the presence of the benzene rings which improve the efficiency of the energy transfer to the cation emissive centres. The prepared polymer complexes were structurally investigated through Fourier transform infrared and X‐ray photoelectron spectroscopies while atomic force microscopy was used to study the morphology of the prepared thin films. Steady‐state fluorescence spectroscopy and absolute PL quantum yield were used for the investigation of the luminescent properties. The impressive PL emission and the convenience of preparation in bulk or thin films could be important arguments for a wide area of applications ranging from photonic conversion materials in optoelectronic devices (light‐emitting diodes, flat‐panel displays) to full‐colour watermarks on special‐purpose papers or PL inks and coatings. © 2019 Society of Chemical Industry     

Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD—both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.     

Designing effective professional development for technology integration in schools

This study aims to explore the critical factors for effective professional development (PD) activities to support teachers' technology integration and suggests a design model: flipped PD. The following questions are investigated: What are the core features of effective teacher PD, what are the implications of core features in effective technology integration PD, and what are the best practices for designing a flipped PD model for preparing teachers to integrate technology into their classrooms? First, we discuss the core features of effective teacher PD: content focus, active learning, coherence, duration, collective participation, and the role of context. Second, we explore design factors in recent technology integration PD studies: learner centred, relevance and reflection, evidence of student learning, support and follow-up, student voice, and initial implementation with teacher leaders. Finally, we present a discussion of our recommendations for a flipped model for technology integration PD.     

11C Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to α-Synuclein Fibrils in vitro and Crosses the Blood-Brain Barrier

There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for ¹¹C radiolabeling using in-situ generated [¹¹C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood–brain barrier and low background binding to the non-pathological brain.     

Ultra-High-Throughput EMS NB-LDPC Decoder with Full-Parallel Node Processing

Journal of Signal Processing Systems - This paper presents an ultra-high-throughput decoder architecture for NB-LDPC codes based on the Hybrid Extended Min-Sum algorithm. We introduce a new...     

Emulsion characteristics of salad dressings as affected by caprine whey protein concentrates

Caprine whey protein concentrates (WPC) were incorporated as emulsifiers in a salad dressing. The concentrates were manufactured by ultrafiltration-diafiltration with or without previous clarification by thermocalcic precipitation. Aggregates obtained in the clarification treatment and a commercial bovine WPC were also used as emulsifiers. Good emulsifying properties of caprine products were observed. Dressings made with caprine products showed higher firmness and stability than dressings made with bovine WPC. Thermocalcic precipitation improved the properties of caprine WPC. Aggregates modified the colour of dressings contributing to a more yellowish aspect. Microstructure of emulsions was affected by the type of protein.