About the sonoluminescent spectral portrait of gasoline water pollution.

Single-bubble sonoluminescence spectra of the following samples were recorded in the modes of standing and moving bubble in liquid near the center of its levitation under the action of ultrasound: water contaminated with additives of commercial gasoline (1.5 - 38 mg·L), water with additives of individual gasoline components (hexane, benzene, toluene, p-xylene, naphthalene, anthracene, and p-terphenyl), and solutions of these gasoline components in hexane. Characteristic bands λ of gasoline component emitters are recorded in the sonoluminescence spectra of a moving bubble for water samples contaminated with additives of commercial gasoline: 290 (p-xylene), 340 (p-terphenyl), 381, 399, 424, 449 (anthracene), and 438, 474, 516, 564 nm (C, a hydrocarbon decomposition product during sonolysis).

Small protein blockers of human IL-6 receptor alpha inhibit proliferation and migration of cancer cells.

Background: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target.

Methods: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display.

Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging.

Background: Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1 lymphocytes. Due to solid tumor heterogeneity of PD-1 populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1 tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.

Perceived Value of a Women's Health Journal Club in Rural Hawai'i.

Objectives: Rural Hawai'i faces a shortage of physicians specializing in women's health. Improving clinician collaboration and access to the scientific literature are potential strategies for improving physician retention in this community. In 2021, a monthly women's health journal club was established for local clinicians and trainees on Hawai'i Island.

Application of Sonotriboluminescence to Determine Arene Molecules in Hydrocarbons.

The sonotriboluminescence of suspensions of terbium(III) and europium(III) sulfates in decane without and in the presence of benzene, toluene and -xylene was studied. The choice of crystals of these lanthanides is due to the fact that they have intense luminescence during mechanical action, and also do not dissolve in hydrocarbon solvents. During ultrasonic exposure to suspensions in pure alkanes, bands of Ln ions and N in the UV region are recorded in the luminescence spectrum.

RIG-I and MDA5 are modulated by bone morphogenetic protein (BMP6) and are essential for restricting Zika virus infection in human Sertoli cells.

Sexual transmission of Zika virus (ZIKV) is associated with virus persistence in the testes and shedding in the seminal fluid for months after recovery. We previously demonstrated that ZIKV can establish long-term replication without causing cytotoxicity in human Sertoli cells (SC), responsible for maintaining the immune privileged compartment of seminiferous tubules. Functional gene expression analyses also predicted activation of multiple virus sensing pathways including TLR3, RIG-I, and MDA5.

Incorporation of the Dry Blossom Flour of L. in the Production of Sponge Cakes.

The present study aims to develop recipe compositions and technology for producing sponge cakes from wholemeal flour, partially replaced with a functional plant component dry blossom flour of L. Three designs of sponge cakes with 5, 10, and 15% content of flour of L. corrected up to 100% with whole-grain oat flour were studied.

Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents.

The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and -negative bacteria, including pathogens and multiresistant strains.

Non-canonical transcription initiation: the expanding universe of transcription initiating substrates.

RNA polymerase (RNAP) is the central enzyme of transcription of the genetic information from DNA into RNA. RNAP recognizes four main substrates: ATP, CTP, GTP and UTP. Experimental evidence from the past several years suggests that, besides these four NTPs, other molecules can be used to initiate transcription: (i) ribooligonucleotides (nanoRNAs) and (ii) coenzymes such as NAD+, NADH, dephospho-CoA and FAD.

The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA.

The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization and translation efficiency, and has been proposed to provide a layer of ‘epitranscriptomic’ gene regulation. Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate ‘cap’ in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD+) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria.

CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability.

Recent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of the voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability. Mutations in the FGF14 gene in humans have been associated with brain disorders that are partially recapitulated in Fgf14(-/-) mice. Thus, signaling pathways that modulate the FGF14:Nav channel interaction may be important therapeutic targets.

Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins.

The advantages offered by established antibiotics in the treatment of infectious diseases are endangered due to the increase in the number of antibiotic-resistant bacterial strains. This leads to a need for new antibacterial compounds. Recently, we discovered a series of compounds termed lipophosphonoxins (LPPOs) that exhibit selective cytotoxicity towards Gram-positive bacteria that include pathogens and resistant strains.

Identifying a kinase network regulating FGF14:Nav1.6 complex assembly using split-luciferase complementation.

Kinases play fundamental roles in the brain. Through complex signaling pathways, kinases regulate the strength of protein:protein interactions (PPI) influencing cell cycle, signal transduction, and electrical activity of neurons. Changes induced by kinases on neuronal excitability, synaptic plasticity and brain connectivity are linked to complex brain disorders, but the molecular mechanisms underlying these cellular events remain for the most part elusive.

Modulation of the FGF14:FGF14 homodimer interaction through short peptide fragments.

Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGF (iFGFs) family and a functionally relevant component of the neuronal voltage-gated Na(+) (Nav) channel complex. Through a monomeric interaction with the intracellular C-terminus of neuronal Nav channels, FGF14 modulates Na(+) currents in an Nav isoform-specific manner serving as a fine-tuning regulator of excitability. Previous studies based on the highly homologous FGF13 homodimer crystal structure have proposed a conserved protein:protein interaction (PPI) interface common to both Nav channel binding and iFGF homodimer formation.

Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres.

A series of conformationally constrained uridine-based nucleoside phosphonic acids containing annealed 1,3-dioxolane and 1,4-dioxane rings and their "open-structure" isosteres were synthesized and evaluated as potential multisubstrate-like inhibitors of the human recombinant thymidine phosphorylase (TP, EC 2.4.2.

[Efficacy of agomelatine in depressive disorders with anxiety].

An open 6-week study on the efficacy of agomelatine in 35 patients with a single depressive episode or recurrent depression (ICD-10) with marked anxiety was carried out. The high efficacy and safety of agomelatine in the treatment of mild and moderate depression concomitant to anxiety disorders was demonstrated. The reduction in depressive symptoms and sleep disorders was noted from the first week of treatment and in anxiety disorders - from the second week.

[The influence of the postoperative nutritional support on immune status in patients undergoing abdominal operations].

At the present day inclusion of the immune enhancing enteral nutrition in the program of the postoperative nutritional support is considered to be the most prospective method of the treatment of intestinal failure, hypermetabolism, hypercatabolism and systemic inflammatory response syndrome in patients undergoing abdominal operations. 60 patients, undergoing gastro-pancreaticoduodenal resections and gastrectomy, were examined. During the postoperative period the first group (experimental group) received standard enteral nutrition.

Bioluminescence methodology for the detection of protein-protein interactions within the voltage-gated sodium channel macromolecular complex.

Protein-protein interactions are critical molecular determinants of ion channel function and emerging targets for pharmacological interventions. Yet, current methodologies for the rapid detection of ion channel macromolecular complexes are still lacking. In this study we have adapted a split-luciferase complementation assay (LCA) for detecting the assembly of the voltage-gated Na+ (Nav) channel C-tail and the intracellular fibroblast growth factor 14 (FGF14), a functionally relevant component of the Nav channelosome that controls gating and targeting of Nav channels through direct interaction with the channel C-tail.

N-phosphonocarbonylpyrrolidine derivatives of guanine: a new class of bi-substrate inhibitors of human purine nucleoside phosphorylase.

A complete series of pyrrolidine nucleotides, (3R)- and (3S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acids and (3S,4R)-, (3R,4S)-, (3S,4S)-, and (3R,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acids, were synthesized and evaluated as potential inhibitors of purine nucleoside phosphorylase (PNP) isolated from peripheral blood mononuclear cells (PBMCs) and cell lines of myeloid and lymphoid origin. Two compounds, (S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acid (2a) and (3S,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acid (6a), were recognized as nanomolar competitive inhibitors of PNP isolated from cell lines with K(i) values within the ranges of 16-100 and 10-24 nM, respectively. The low (MESG)K(i) and (Pi)K(i) values of both compounds for PNP isolated from PBMCs suggest that these compounds could be bisubstrate inhibitors that occupy both the phosphate and nucleoside binding sites of the enzyme.

Activation of human RNase L by 2'- and 5'-O-methylphosphonate-modified oligoadenylates.

To determine the influence of internucleotide linkage and sugar ring conformation, and the role of 5'-terminal phosphate, on the activation of human RNase L, a series of 2'- and 5'-O-methylphosphonate-modified tetramers were synthesized from appropriate monomeric units and evaluated for their ability to activate human RNase L. Tetramers pAAAp(c)X modified by ribo, arabino or xylo 5'-phosphonate unit p(c)X activated RNase L with efficiency comparable to that of natural activator. Moreover, incorporation of phosphonate linkages ensured the stability against cleavage by nucleases.

Synthesis of novel deoxynucleoside S-methylphosphonic acids using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new equivalent of mercaptomethylphosphonate.

The synthesis of the novel nucleotide analogues 5'-deoxynucleoside-5'-S-methylphosphonates, starting from 5'-deoxy-5'-haloribonucleosides, 5'-O-tosylribonucleosides, and 2'-O-triflylnucleosides, is described. The phosphonothiolation of these compounds was achieved using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new, odourless, and efficient equivalent of mercaptomethylphosphonate. The thiolate anion of mercaptomethylphosphonate was generated in situ from the isothiouronium salt in both protic and aprotic solvents using two equivalents of sodium iso-propoxide.

Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.

Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC 2.4.2.

Substrate specificity of thymidine phosphorylase of E. coli: role of hydroxyl groups.

Substrate specificity of E. coli thymidine phosphorylase to pyrimidine nucleoside modified at 5'-, 3'-, and 2'-positions of sugar moiety has been studied. Equilibrium (K(eq)) and kinetics constants of phosphorolysis reaction of nucleosides were measured.