Nuclear RNA Decay Pathways Aid Rapid Remodeling of Gene Expression in Yeast.

In budding yeast, the nuclear RNA surveillance system is active on all pre-mRNA transcripts and modulated by nutrient availability. To test the role of nuclear surveillance in reprogramming gene expression, we identified transcriptome-wide binding sites for RNA polymerase II and the exosome cofactors Mtr4 (TRAMP complex) and Nab3 (NNS complex) by UV crosslinking immediately following glucose withdrawal (0, 4, and 8 min). In glucose, mRNA binding by Nab3 and Mtr4 was mainly restricted to promoter-proximal sites, reflecting early transcription termination. Following glucose withdrawal, many growth-related mRNAs showed reduced transcription but increased Nab3 binding, accompanied by downstream recruitment of Mtr4, and oligo(A) tailing. We conclude that transcription termination is followed by TRAMP-mediated RNA decay. Upregulated transcripts evaded increased surveillance factor binding following glucose withdrawal. Some upregulated genes showed use of alternative transcription starts to bypass strong NNS binding sites. We conclude that nuclear surveillance pathways regulate both positive and negative responses to glucose availability.

A systematic analysis of Trypanosoma brucei chromatin factors identifies novel protein interaction networks associated with sites of transcription initiation and termination.

Nucleosomes composed of histones are the fundamental units around which DNA is wrapped to form chromatin. Transcriptionally active euchromatin or repressive heterochromatin is regulated in part by the addition or removal of histone post-translational modifications (PTMs) by "writer" and "eraser" enzymes, respectively. Nucleosomal PTMs are recognized by a variety of "reader" proteins that alter gene expression accordingly. The histone tails of the evolutionarily divergent eukaryotic parasite Trypanosoma brucei have atypical sequences and PTMs distinct from those often considered universally conserved. Here we identify 65 predicted readers, writers, and erasers of histone acetylation and methylation encoded in the T. brucei genome and, by epitope tagging, systemically localize 60 of them in the parasite's bloodstream form. ChIP-seq shows that 15 candidate proteins associate with regions of RNAPII transcription initiation. Eight other proteins show a distinct distribution with specific peaks at a subset of RNAPII transcription termination regions marked by RNAPIII-transcribed tRNA and snRNA genes. Proteomic analyses identify distinct protein interaction networks comprising known chromatin regulators and novel trypanosome-specific components. Notably, several SET- and Bromo-domain protein networks suggest parallels to RNAPII promoter-associated complexes in conventional eukaryotes. Further, we identify likely components of TbSWR1 and TbNuA4 complexes whose enrichment coincides with the SWR1-C exchange substrate H2A.Z at RNAPII transcription start regions. The systematic approach used provides details of the composition and organization of the chromatin regulatory machinery in T. brucei and establishes a route to explore divergence from eukaryotic norms in an evolutionarily ancient but experimentally accessible eukaryote.

New Water-Soluble Poly(propylene imine) Dendrimer Modified with 4-Sulfo-1,8-naphthalimide Units: Sensing Properties and Logic Gates Mimicking.

A new water-soluble poly(propylene imine) dendrimer (PPI) modified with 4-sulfo-1,8-naphthalimid units (SNID) and its related structure monomer analog (SNIM) has been prepared by a simple synthesis. The aqueous solution of the monomer exhibited aggregation-induced emission (AIE) at 395 nm, while the dendrimer emitted at 470 nm due to an excimer formation beside the AIE at 395 nm. Fluorescence emission of the aqueous solution of either SNIM or SNID was significantly affected by traces of different miscible organic solvents, and the limits of detection were found to be less than 0.05% (v/v). Moreover, SNID exhibited the function to execute molecular size-based logic gates where it mimics XNOR and INHIBIT logic gates using water and ethanol as inputs and the AIE/excimer emissions as outputs. Hence, the concomitant execution of both XNOR and INHIBIT enables SNID to mimic digital comparators.

Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells.

The activity and interacting ability of a polyamidoamine (PAMAM) dendrimer modified with 4-N-methylpiperazine-1,8-naphthalimide units (termed D) and complexed by Cu(ii) ions, towards healthy and cancer cells were studied. Comparative electron paramagnetic resonance (EPR) studies of the Cu(ii)-D complex are presented: coordination mode, chemical structure, flexibility and stability of these complexes, in the absence and presence of myeloid cancer cells and peripheral blood mononuclear cells (PBMC). The interactions of Cu(ii) ions in the biological media at different equilibrium times were studied, highlighting different stability and interacting conditions with the cells. Furthermore, flow cytometry and confocal analysis, trace the peculiar properties of the dendrimers in PBMC and U937 cells. Indeed, a new probe (Fly) was used as a potential fluorescent tool for biological imaging of Cu(ii). The study highlights that dendrimer and, mainly, the Cu(ii) metallodendrimer are cytotoxic agents for the cells, specifically for U937 tumor cells, inducing mitochondrial dysfunction, ROS increase and lysosome involvement. The metallodendrimer shows antitumor selectivity, fewer affecting healthy PBMC, inducing a massive apoptotic cell death on U937 cells, in line with the high stability of this complex, as verified by EPR studies. The results underline the potentiality of this metallodendrimer to be used as anticancer drug.

Self-Associated 1,8-Naphthalimide as a Selective Fluorescent Chemosensor for Detection of High pH in Aqueous Solutions and Their Hg2+ Contamination.

A novel diamino triazine based 1,8-naphthalimide (NI-DAT) has been designed and synthesized. Its photophysical properties have been investigated in different solvents and its sensory capability evaluated. The fluorescence emission of NI-DAT is significantly impacted by the solvent polarity due to its inherent intramolecular charge transfer character. Moreover, the fluorescence emission quenched at higher pH as a result of photo-induced electron transfer (PET) from triazine moiety to 1,8-naphthalimide after cleaving hydrogen bonds in the self-associated dimers. Furthermore, the new chemosensor exhibited a good selectivity and sensitivity towards Hg2+ among all the used various cations and anions in the aqueous solution of ethanol (5:1, v/v, pH = 7.2, Tampon buffer). NI-DAT emission at 540 nm was quenched remarkably only by Hg2+, even in the presence of other cations or anions as interfering analytes. Job's plot revealed a 2:1 stoichiometric ratio for NI-DAT/Hg2+ complex, respectively.

Enhanced Photodynamic Efficacy Using 1,8-Naphthalimides: Potential Application in Antibacterial Photodynamic Therapy.

This study addresses the need for antibacterial medication that can overcome the current problems of antibiotics. It does so by suggesting two 1,8-naphthalimides (NI1 and NI2) containing a pyridinium nucleus become attached to the imide-nitrogen atom via a methylene spacer. Those fluorescent derivatives are covalently bonded to the surface of a chloroacetyl-chloride-modified cotton fabric. The iodometric method was used to study the generation of singlet oxygen (1O2) by irradiation of KI in the presence of monomeric 1,8-naphthalimides and the dyed textile material. Both compounds generated reactive singlet oxygen, and their activity was preserved even after they were deposited onto the cotton fabric. The antibacterial activity of NI1 and NI2 in solution and after their covalent bonding to the cotton fabric was investigated. In vitro tests were performed against the model gram-positive bacteria B. cereus and gram-negative P. aeruginosa bacteria in dark and under light iradiation. Compound NI2 showed higher antibacterial activity than compound NI1. The light irradiation enhanced the antimicrobial activity of the compounds, with a better effect achieved against B. cereus.

Study of Novel Peptides for Antimicrobial Protection in Solution and on Cotton Fabric.

Some new N- and C-modified biomolecular peptide analogues of both VV-hemorphin-5 and VV-hemorphin-7 with varied amino acids (Cys, Glu, His), 1-adamantanecarboxylic acid, and niacin (nicotinic acid) were synthesized by solid-phase peptide synthesis-Fmoc (9-fluorenylmethoxy-carbonyl) chemistry and were characterized in water solutions with different pH using spectroscopic and electrochemical techniques. Basic physicochemical properties related to the elucidation of the peptide structure at physiological pH have been also studied. The results showed that the interaction of peptide compounds with light and electricity preserves the structural and conformational integrity of the compounds in the solutions. Moreover, textile cotton fibers were modified with the new compounds and the binding of the peptides to the surface of the material was proved by FTIR and SEM analysis. Washing the material with an alkaline soap solution did not show a violation of the modified structure of the cotton. Antiviral activity against the human respiratory syncytial virus (HRSV-S2) and human adenovirus serotype 5 (HAdV-5), the antimicrobial activity against B. cereus and P. aeruginosa used as model bacterial strains and cytotoxic effect of the peptide derivatives and modified cotton textile material has been evaluated. Antimicrobial tests showed promising activity of the newly synthesized compounds against the used Gram-positive and Gram-negative bacteria. The compounds C-V, H-V, AC-V, and AH-V were found slightly more active than NH7C and NCH7. The activity has been retained after the deposition of the compounds on cotton fibers.

Synthesis of New Modified with Rhodamine B Peptides for Antiviral Protection of Textile Materials.

Here we report on the synthesis and characterization of three new N-modified analogues of hemorphin-4 with rhodamine B. Modified with chloroacetyl, chloride cotton fabric has been dyed and color coordinates of the obtained textile materials were determined. Antiviral and virucidal activities of both the peptide-rhodamine B compounds and the dyed textile material were studied. Basic physicochemical properties (acid-base behavior, solvent influence, kinetics) related to the elucidation of structural activity of the new modified peptides based on their steric open/closed ring effect were studied. The obtained results lead to the conclusion that in protic solvent with change in pH of the environment, direct control over the dyeing of textiles can be achieved. Both the new hybrid peptide compounds and the modification of functionalized textile materials with these bioactive hemorphins showed virucidal activity against the human respiratory syncytial virus (HRSV-S2) and human adenovirus serotype 5 (HAdV-5) for different time intervals (30 and 60 min) and the most active compound was Rh-3.

Synthesis, spectral properties and antimicrobial activity of a new cationic water-soluble pH-dependent poly(propylene imine) dendrimer modified with 1,8-naphthalimides.

A three-step synthesis was implemented to prepare a quaternary ammonium functionalized blue fluorescent poly(propylene imine) dendrimer modified with pyridinium salt of 4-acylamino-1,8-naphthalimide. The new cationic dendrimer absorbs in the ultraviolet light region and emits blue fluorescence. Its spectral characteristics in organic solvents and in an aqueous solution were studied. The influence of pH on the fluorescence intensity of the dendrimer was established with regard to its use as a pH sensor. The effect of hydroxyl ions on the absorption and fluorescence spectra in dry N,N-dimethylformamide was also investigated. The antimicrobial activity of the dendrimer was assessed against model pathogenic microorganisms in agar, liquid medium, and after its deposition on cotton fabric.

Spectral Characteristics and Sensor Ability of a New 1,8-Naphthalimide and Its Copolymer with Styrene.

In this study, a novel 6-(allylamino)-2-(2-(dimethylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (NI3) was synthesized and characterized. Its copolymer with styrene was also obtained. The photophysical characteristics of NI3 were investigated in organic solvents and the results were compared with those of its structural analogue, 2-allyl-6-((2-(dimethylamino)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (NI4). The influences of the pH in the medium and different metal ions on the fluorescent intensity of monomers and polymers were also investigated. Computational tools (DFT and TDDFT calculations) were employed when studying the structure and properties of the 1,8-naphthalimide-based chromophores. Although the position of the N,N-dimethylaminoethylamine receptor fragment did not significantly impact proton detection, it was still important for detecting metal ion sensor ability, especially for monomeric 1,8-naphthalimide structures and their copolymers with styrene.

Metal-Peptide Complexes with Antimicrobial Potential for Cotton Fiber Protection.

A study of the formation of copper (II) complexes with hemorphin peptide motifs in alkalic water solutions is presented. The effect of the peptide ligand on the complexing properties of the Cu (II) ion was quantified by giving the stoichiometry and stability of the complex compounds in the medium in which they are formed using voltammetric (cyclic) and spectral (UV-Vis and fluorimetric) analytical techniques. The resulting complexes were examined via IR spectroscopy to detect M-N and M-O oscillations and using the EPR approach in solution and in the solid phase to view the coordination and ligand binding regime. The possibility of the synergistic action of copper ions in the antivirus protection processes of cotton fibers coated in the same solvent with the newly obtained complex compounds was also investigated. One of the advantages is the formation of the complexes in an environment where the immobilization takes place, which contributes to increasing the efficiency of the process. The obtained results may serve as an aid for future more detailed biological studies of structure-activity relationships (SARs).

Antimicrobial Properties of Chitosan-Modified Cotton Fabric Treated with Aldehydes and Zinc Oxide Particles.

Chitosan is a natural biopolymer with a proven ability to impart textile materials with antimicrobial properties when loaded onto them. The mechanism of its bacteriological activity depends on the contact between the positive and negative charges of the amino groups located on the surface of the microbes. Unfortunately, the type of microorganisms and pH influence this action-shortcomings that can be avoided by chitosan modification and by loading its film with substances possessing antimicrobial properties. In this study, chitosan was modified with benzaldehyde and crosslinked with glutaraldehyde to form a film on the surface of cotton fabric (CB). Also, another material was obtained by including zinc oxide particles (CBZ) synthesized in situ into the chitosan coating. The performed analyses (contact angle measurement, optical and scanning electron microscopy, FTIR, XRD, and thermal analysis) evidenced the modification of the cotton fabric and the alteration of the film properties after zinc oxide inclusion. A comparison of the antimicrobial properties of the new CB with materials prepared with chitosan without benzaldehyde from our previous study verified the influence of the hydrophobicity and surface roughness of the fabric surface on the enhancement of antimicrobial activity. The microbial growth inhibition increased in the following order: fungal strain Candida lipolytica >Gram-positive bacteria Bacillus cereus >Gram-negative bacteria Pseudomonas aeruginosa. The samples containing zinc oxide particles completely inhibited the growth of all three model strains. The virucidal activity of the CB was higher against human adenovirus serotype 5 (HAdV-5) than against human respiratory syncytial virus (HRSV-S2) after 60 min of exposure. The CBZ displayed higher virucidal activity with a Δlog of 0.9 against both viruses.

Design of a Composite Based on Polyamide Fabric-Hydrogel-Zinc Oxide Particles to Act as Adsorbent and Photocatalyst.

Surface-initiated photopolymerization has been run to synthesize a hydrogel with ZnO particles distributed uniformly along its structure, which has been loaded onto a polyamide fabric. Three samples have been obtained at different concentrations of zinc nitrate (10% (sample PA10); 20% (sample PA20) and 30% (sample PA30) of the weight of the fabric, respectively)) and subjected to gravimetric analysis, scanning electron microscopy and transmission electron microscopy. The effect of the adsorption parameters of the composite material on the removal Drimaren Rot K-7B dye from water has been studied. The Freundlich isotherm describes this process better than the Langmuir isotherm. As the results of the adsorption kinetics show, the process fits well with a pseudo-second-order equation and depends both on the boundary layer and on the structure of the adsorbent itself. The thermodynamic parameters have demonstrated that the process is endothermic and physical. When exposed to ultraviolet light, the discoloration of the dye solution accelerates due to the photocatalytic properties of the composite materials. The addition of H2O2 also speeds up further the process, while the reuse of the materials slows it down, gradually changing the kinetic parameters. The reaction has been attributed to first-order kinetic model, when the active centers of the materials and the number of oxidative radicals formed are numerous and to the second-order kinetic model at a lower reaction activity. Moreover, 52% decolorization of the dye solution (50 mg L-1) in the dark was achieved from composite material PA 30 (13.3 g L-1) in 120 min and 89% under UV light irradiation. The H2O2 addition (0.14 mmol L-1) enhanced it up to 98%. In the second and third use of the photocatalyst, the dye removal decreased to 80% and 60%. Composite material PA30 exhibits antibacterial activity against Gram-negative bacteria E. coli, being most effective at eliminating Gram-positive bacteria S. aureus.

The SPARC complex defines RNAPII promoters in Trypanosoma brucei.

Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid Trypanosoma brucei. Our analyses revealed that the predicted histone methyltransferase SET27 and the Chromodomain protein CRD1 are tightly concentrated at RNAPII transcription start regions (TSRs). Here, we report that SET27 and CRD1, together with four previously uncharacterized constituents, form the SET27 promoter-associated regulatory complex (SPARC), which is specifically enriched at TSRs. SET27 loss leads to aberrant RNAPII recruitment to promoter sites, accumulation of polyadenylated transcripts upstream of normal transcription start sites, and conversion of some normally unidirectional promoters to bidirectional promoters. Transcriptome analysis in the absence of SET27 revealed upregulated mRNA expression in the vicinity of SPARC peaks within the main body of chromosomes in addition to derepression of genes encoding variant surface glycoproteins (VSGs) located in subtelomeric regions. These analyses uncover a novel chromatin-associated complex required to establish accurate promoter position and directionality.

Textile Materials Modified with Stimuli-Responsive Drug Carrier for Skin Topical and Transdermal Delivery.

Textile materials, as a suitable matrix for different active substances facilitating their gradual release, can have an important role in skin topical or transdermal therapy. Characterized by compositional and structural variety, those materials readily meet the requirements for applications in specific therapies. Aromatherapy, antimicrobial substances and painkillers, hormone therapy, psoriasis treatment, atopic dermatitis, melanoma, etc., are some of the areas where textiles can be used as carriers. There are versatile optional methods for loading the biologically active substances onto textile materials. The oldest ones are by exhaustion, spraying, and a pad-dry-cure method. Another widespread method is the microencapsulation. The modification of textile materials with stimuli-responsive polymers is a perspective route to obtaining new textiles of improved multifunctional properties and intelligent response. In recent years, research has focused on new structures such as dendrimers, polymer micelles, liposomes, polymer nanoparticles, and hydrogels. Numerous functional groups and the ability to encapsulate different substances define dendrimer molecules as promising carriers for drug delivery. Hydrogels are also high molecular hydrophilic structures that can be used to modify textile material. They absorb a large amount of water or biological fluids and can support the delivery of medicines. These characteristics correspond to one of the current trends in the development of materials used in transdermal therapy, namely production of intelligent materials, i.e., such that allow controlled concentration and time delivery of the active substance and simultaneous visualization of the process, which can only be achieved with appropriate and purposeful modification of the textile material.

Pollutants Sorbent Made of Cotton Fabric Modified with Chitosan-Glutaraldehyde and Zinc Oxide Particles.

The paper reports on the preparation of composite materials by modifying cotton fabric with a layer of crosslinked glutaraldehyde chitosan containing zinc oxide particles. The ability of chitosan to form complexes with zinc ions has been used to control the size, structure, and distribution of the particles on the fiber surface. The three different obtained materials have been characterized by optical and scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and fluorescent analysis. It has been found that the interaction of the ZnO particles with the functional groups of chitosan affects its swelling ability in water and thus determines its sorption properties. The capacity of the materials to wipe water-soluble (textile reactive dye) and water-insoluble (crude oil and oil products) contaminants has been compared. The effect that the amount of zinc oxide has on the ability of the materials to remove contaminants has also been studied. The possibility for adsorption-desorption of the crude oil and reuse of the sorbent material has been investigated as well.

Cotton Fabric Modified with a PAMAM Dendrimer with Encapsulated Copper Nanoparticles: Antimicrobial Activity.

A new methodology for modifying textile materials with dendrimers containing nanoparticles was developed. This involved a combination of eosin Y and N-methyldiethanolamine (MDEA) for reducing the copper ions in the dendrimer complex by enabling a photochemical reaction under visible light and ambient conditions. The conversion of copper ions into nanoparticles was monitored using scanning electron microscopy (SEM) and by performing colorimetric, fluorescence, and electron paramagnetic resonance (EPR) studies. Regardless of the concentration of the photoinitiator eosin Y, it discolored completely upon illumination. Three types of cotton fabrics were compared as antimicrobial materials against Bacillus cereus. One of the fabrics was dyed with a first-generation PAMAM dendrimer which had been functionalized with eight 1,8-naphthalimide fluorophores. Another fabric was dyed with a dendrimer-copper complex, and the third was treated by conversion of the complex into copper nanoparticles encapsulated into the dendrimer. An enhancement in the antimicrobial activity of the textiles was achieved at higher dendrimer concentrations, under illumination with visible light. The fabric modified with the copper nanoparticles encapsulated inside the dendrimer exhibited the best antibacterial activity because it had two photosensitizers (PS), as both 1,8-naphthalimide fluorophores and copper nanoparticles were contained in the dendrimer molecules. The presence of oxygen and suitable illumination activated the photosensitizers to generate the reactive oxygen species (singlet oxygen (1O2) and other oxygenated products, e.g., anion radicals, hydroxyl radicals, and hydrogen peroxide) responsible for destroying the bacteria.

Synthesis, spectral characteristics and sensor ability of new polyamidoamine dendrimers, modified with curcumin.

To prepare a novel highly photo-stable fluorescent chemosensor, curcumin was successfully immobilized to polyamidoamine dendrimer of zero (S1), first (S2) and second (S3) generations conjugated-UV absorber moieties. Chemical structure of synthesized chemosensors were well-analysed by FTIR, 1H-NMR, 13CNMR, elemental analysis, DSC and UV-vis techniques. Photo-physical characteristics and solvatochromism effect of three novel chemosensors in organic solvents with different dielectric constants ranged 2.21-37.78 were studied. The pH determination ability of S1, S2 and S3 in the range of 2-12 were also examined. Newly synthesized materials were employed for detection of different metal cations including Ag+, Ba2+, Cu2+, Ca2+, Cd2+, Fe3+, Hg2+, Ni2+, Pb2+ and Zn2+ and their possibility to apply as a cation chemosensor were evaluated. The results showed significant changes in their fluorescence intensity upon the different pHs and cations indicating their possibility to apply as a pH and metal cation chemosensor. Among the new chemosensors under study, S1 represented high sensitivity to pH in the range of 4-8 and high selectivity for Cu2+ over the other cations.

Hyperbranched Polymers Modified with Dansyl Units and Their Cu(II) Complexes. Bioactivity Studies.

Two new copper complexes of hyperbranched polymers modified with dansyl units were synthesized and characterized by infrared spectroscopy (IR) and electron paramagnetic resonance (EPR) techniques. It was found that copper ions coordinate predominantly with nitrogen or oxygen atoms of the polymer molecule. The place of the formation of complexes and the number of copper ions involved depend on the chemical structure of the polymer. The antimicrobial activity of the new polymers and their Cu(II) complexes was tested against Gram-negative and Gram-positive bacterial and fungal strains. Copper complexes were found to have activity better than that of the corresponding ligands. The deposition of the modified branched polymers onto cotton fabrics prevents the formation of bacterial biofilms, which indicates that the studied polymers can find application in antibacterial textiles.

A New Bioactive Complex between Zn(II) and a Fluorescent Symmetrical Benzanthrone Tripod for an Antibacterial Textile.

A new fluorescent Zn(II) complex of symmetrical tripod form based on a 3-substituted benzanthrone (BT) has been synthesized and characterised. The basic photophysical properties of the new metal complex have been determined. It has been found by fluorescence spectroscopy that, one zinc ion forms a complex with the tripod ligand. The surface morphology of the ligand and its Zn(II) complex has been investigated by the scanning electron microscopy (SEM) technique. X-ray photoelectron spectroscopy (XPS) has been used for the characterisation of the chemical composition of the complex surfaces. The antibacterial activity of the Zn(II) complex has been investigated in solution and upon its deposition onto a cotton fabric. A reduction of biofilm formation on the surface of the cotton fabric has been observed compared to the non-treated cotton material. The results obtained demonstrate that the studied Zn(II) complex possesses good antimicrobial activity being most effective against the used Gram-positive bacteria.