A dual-app nucleoside probe reports G-quadruplex formation and ligand binding in the long terminal repeat of HIV-1 proviral genome.

We have developed a dual-app nucleoside analog, 5-selenophene-modified 2'-deoxyuridine (dU), to probe the structure and ligand-binding properties of a G-rich segment present in the long terminal repeat (LTR) of the HIV-1 proviral DNA promoter region. The nucleoside probe is made of an environment-responsive fluorophore and X-ray crystallography phasing label (Se atom). dU incorporated into LTR-IV sequence, fluorescently reports the formation of G-quadruplex (GQ) structure without affecting the native fold.

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides.

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l-α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application.

biofilm formation on endotracheal tubes requires multiple two-component systems.

Indwelling medical devices such as endotracheal tubes (ETTs), urinary catheters, vascular access devices, tracheostomies and feeding tubes are often associated with hospital-acquired infections. Bacterial biofilm formed on the ETTs in intubated patients is a significant risk factor associated with ventilator-associated pneumonia. is one of the four frequently encountered bacteria responsible for causing pneumonia, and the biofilm formation on ETTs.

Naturally occurring and tumor-associated variants of RNF167 promote lysosomal exocytosis and plasma membrane resealing.

Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized.

A compositional neural code in high-level visual cortex can explain jumbled word reading.

We read jubmled wrods effortlessly, but the neural correlates of this remarkable ability remain poorly understood. We hypothesized that viewing a jumbled word activates a visual representation that is compared to known words. To test this hypothesis, we devised a purely visual model in which neurons tuned to letter shape respond to longer strings in a compositional manner by linearly summing letter responses.

Stacking-Order-Driven Optical Properties and Carrier Dynamics in ReS.

Two distinct stacking orders in ReS are identified without ambiguity and their influence on vibrational, optical properties and carrier dynamics are investigated. With atomic resolution scanning transmission electron microscopy (STEM), two stacking orders are determined as AA stacking with negligible displacement across layers, and AB stacking with about a one-unit cell displacement along the a axis. First-principles calculations confirm that these two stacking orders correspond to two local energy minima.

Effect of , Coordination and Ru Halide Bond in Enhancing Selective Toxicity of a Tyramine-Based Ru (-Cymene) Complex.

Ruthenium compounds are promising anticancer candidates owing to their lower side-effects and encouraging activities against resistant tumors. Half-sandwich piano-stool type Ru compounds of general formula [(L)Ru(η-arene)(X)] (L = chelating bidentate ligand, X = halide) have exhibited significant therapeutic potential against cisplatin-resistant tumor cell lines. In Ru (-cymene) based complexes, the change of the halide leaving group has led to several interesting features, viz.

Mechanistic Insights into an Unusual Side-Chain-Mediated N-C Bond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin.

Conopressin, a nonapeptide disulfide CFIRNCPKG amide present in cone snail venom, undergoes a facile cleavage at the Cys6-Pro7 peptide bond to yield a disulfide bridged ion. Analysis of the mass spectral fragmentation pattern reveals the presence of a major fragment ion, which is unambiguously assigned as the tripeptide sequence IRN amide. The sequence dependence of this unusual fragmentation process has been investigated by comparing it with the fragmentation patterns of related peptides, oxytocin (CYIQNCPLG amide), Lys-vasopressin (CYFQNCPKG amide), and a series of synthetic analogues.

Chemoselective and Site-Selective Lysine-Directed Lysine Modification Enables Single-Site Labeling of Native Proteins.

The necessity for precision labeling of proteins emerged during the efforts to understand and regulate their structure and function. It demands selective attachment of tags such as affinity probes, fluorophores, and potent cytotoxins. Here, we report a method that enables single-site labeling of a high-frequency Lys residue in the native proteins.

Shear stress rosettes capture the complex flow physics in diseased arteries.

Wall shear stress (WSS) is an important parameter in arterial mechanobiology. Various flow metrics, such as time averaged WSS (TAWSS), oscillatory shear index (OSI), and transWSS, have been used to characterize and relate possible WSS variations in arterial diseases like aneurysms and atherosclerosis. We use a graphical representation of WSS using shear rosettes to map temporal changes in the flow dynamics during a cardiac cycle at any spatial location on the vessel surface.

Acetamidinium-Substituted Methylammonium Lead Iodide Perovskite Solar Cells with Higher Open-Circuit Voltage and Improved Intrinsic Stability.

We report acetamidinium (AA)-substituted methylammonium (MA) lead iodide perovskite solar cells. AA has a restricted C-N bond rotation because of delocalized π-electron cloud over the N-C-N bond and the presence of an additional N-H···I bond (4H-bond in AA as compared to 3H-bond in MA). These bonding structures strengthen the electrostatic interaction and stabilize the AA cation inside the perovskite matrix.

Characterization of (Boc-Cys/Sec-NHMe) and (Boc-Cys/Sec-OMe) : Evidence of local conformational difference between disulfide and diselenide.

Conformations of disulfide and diselenide were compared in (Boc-Cys/Sec-NHMe) and (Boc-Cys/Sec-OMe) using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, density functional theory (DFT), and circular dichroism (CD) spectroscopy. Conformations of disulfide/diselenide in polypeptides are defined based on the sign of side chain torsion angle χ (-CH -S/Se-S/Se-CH -); negative indicates left-handed and positive indicates right-handed orientation. In the crystals of (Boc-Cys-OMe) and (Boc-Sec-OMe) , the disulfide exhibits a left-handed and the diselenide a right-handed orientation.

Cone snail analogs of the pituitary hormones oxytocin/vasopressin and their carrier protein neurophysin. Proteomic and transcriptomic identification of conopressins and conophysins.

Transcriptomic analysis of cone snail venom duct tissue has permitted the identification of diverse conopressin/conophysin precursor sequences from seven distinct Conus species. Multiple precursor isoforms are present in C.monile, C.

A trans-dichloridoplatinum(II) complex of a monodentate nitrogen mustard: Synthesis, stability and cytotoxicity studies.

A trans-dichloridoplatinum(II) complex, trans-[PtCl(L)(DMSO)] (1) of a monodentate nitrogen mustard, bis(2-chloroethyl)amine (L), was synthesized by the reaction of cis-[PtCl(DMSO)] &L.HCl in presence of EtN. 1 was characterised by NMR, FT-IR and elemental analysis.

Triplet Decay Dynamics in Sulfur-Substituted Thymine: How Position of Substitution Matters.

Sulfur-substituted analogues of thymine are of three types depending on the position of sulfur substitution: 2-thiothymine (2tThy), 4-thothymine (4tThy), and 2,4-dithiothymine (dtThy). These molecules, on photoexcitation, are known to form in their triplet state with near unity yield. Consequently, they are able to photosensitize ground state molecular oxygen to singlet oxygen, a property which makes them potential drugs for photodynamic therapy (PDT).

Synthesis and biochemical evaluation of -Thymine -Phosphate (-TTP).

Deoxyribonucleoside triphosphates (dNTPs) are building blocks for the biosynthesis of DNA. Various modified dNTPs' analogs have synthesized by structural changes of nucleoside's susgar and nucleobases and employed for synthesis of modified DNA. A very few modified dNTPs have prepared from non-sugar nucleoside analogs.

Crystal structure, DNA crosslinking and photo-induced cytotoxicity of oxovanadium(IV) conjugates of boron-dipyrromethene.

Cis-dichloro-oxovanadium(IV) complexes [VO(L/L)Cl], where L is N-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4ʎ,5ʎ-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 1 and L is N-(4-(5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-5H-4ʎ,5ʎ-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 2) having 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene as boron-dipyrromethene (BODIPY) appended dipicolylamine bases were prepared, characterized and their photocytotoxicity studied. X-ray crystal structure of 1 showed distorted octahedral geometry with a VONCl core having Cl-V-Cl angle of 91.93(4)°.

Pericytes enable effective angiogenesis in the presence of proinflammatory signals.

Angiogenesis frequently occurs in the context of acute or persistent inflammation. The complex interplay of proinflammatory and proangiogenic cues is only partially understood. Using an experimental model, permitting exposure of developing blood vessel sprouts to multiple combinations of diverse biochemical stimuli and juxtacrine cell interactions, we present evidence that a proinflammatory cytokine, tumor necrosis factor (TNF), can have both proangiogenic and antiangiogenic effects, depending on the dose and the presence of pericytes.

A convenient route to synthesize -(isobutyryl)-9-(carboxymethyl)guanine for -PNA backbone.

Synthesis of exclusive -(isobutyryl)-9-(carboxymethyl)guanine, an important moiety for peptide nucleic acid synthesis has been reported through a high-yielding reaction scheme starting from 6-chloro-2-amino purine. Crystal structures of two intermediates confirmed the formation of 9-regioisomer. This new synthetic route can potentially replace the conventional tedious method with moderate overall yield.

DFT based engineering of N-heterocyclic carbenes to exacerbate its activity for SO fixation and storage.

Carbene compounds are very reactive to SO which assert their candidature to seize this greenhouse gas. Unfortunately, most of the carbenes which produce S,S-dioxide with SO, undergo dissociation to yield ketone derivative and SO through an intermediate formation of oxathiirane S-oxide derivative. Thus, carbenes are excluded from the list of catalyst for SO fixation and storage technology.

Pregabalin peptides: conformational comparison of γ- and γ-substituted γ-amino acids in αγααα pentapeptides.

Gamma-aminobutyric acid (GABA, gammaAbu), an unsubstituted gamma-amino acid, is an important inhibitory neurotransmitter in the mammalian brain. The role of GABA in the treatment of epilepsy has triggered a great deal of interest in substituted gamma-amino acids, which may serve as GABA analogs, acting as inhibitors of GABA aminotransferase. Pregabalin (Pgn), a well-known antiepileptic drug, is also a beta-substituted gamma3-amino acid.

One-Dimensional Quasicrystals with Power-Law Hopping.

One-dimensional quasiperiodic systems with power-law hopping, 1/r^{a}, differ from both the standard Aubry-André (AA) model and from power-law systems with uncorrelated disorder. Whereas in the AA model all single-particle states undergo a transition from ergodic to localized at a critical quasidisorder strength, short-range power-law hops with a>1 can result in mobility edges. We find that there is no localization for long-range hops with a≤1, in contrast to the case of uncorrelated disorder.

New isoniazid derivatives with improved pharmaco-toxicological profile: Obtaining, characterization and biological evaluation.

Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs.

Hormonal regulation and function of an RNA helicase, Ddx5 in corpus luteum of adult Wistar rats.

Corpus luteum (CL) is an endocrine tissue involved in regulation of reproductive cycle and early pregnancy establishment. In the present study DEAD-box helicase-5 (Ddx5), a member of the DEAD box family of RNA helicases was investigated for its expression, regulation and function in CL of Wistar rats. Ddx5 was expressed in adult rat CL.