Closing the Gap: How Psychological Distance Influences Willingness to Engage in Risky COVID Behavior.

Pandemics, and other risk-related contexts, require dynamic changes in behavior as situations develop. Human behavior is influenced by both explicit (cognitive) and implicit (intuitive) factors. In this study, we used psychological distance as a lens to understand what influences our decision-making with regard to risk in the context of COVID-19.

Spectroscopic, biochemical and computational studies of bioactive DNA minor groove binders targeting 5'-WGWWCW-3' motif.

Spectroscopic, biochemical, and computational modelling studies have been used to assess the binding capability of a set of minor groove binding (MGB) ligands against the self-complementary DNA sequences 5'-d(CGCACTAGTGCG)-3' and 5'-d(CGCAGTACTGCG)-3'. The ligands were carefully designed to target the DNA response element, 5'-WGWWCW-3', the binding site for several nuclear receptors. Basic 1D H NMR spectra of the DNA samples prepared with three MGB ligands show subtle variations suggestive of how each ligand associates with the double helical structure of both DNA sequences.

COVID-19 Personal Protective Behaviors during Large Social Events: The Value of Behavioral Observations.

Within the context of reopening society in the summer of 2021, as the UK moved away from 'lockdowns', the Government of Wales piloted the return of organized 'mass gatherings' of people at a number of test events. The current study reports behavioral observations that were made at two of the test events to inform this process. The researchers were particularly interested in four key factors: how (1) context within a venue, (2) environmental design, (3) staffing and social norms, and (4) time across an event, affected the personal protective behaviors of social distancing and face-covering use.

A scoping review of community-based mental health intervention for children and adolescents in South Asia.

Children and adolescents in South Asia are exposed to significant mental health risks. Yet, policy to prevent or treat youth mental health problems in this context is underdeveloped, and services are difficult to access. Community-based mental health treatment may offer a potential solution, by increasing resource capacity in deprived settings.

Insights into the Spectrum of Activity and Mechanism of Action of MGB-BP-3.

MGB-BP-3 is a potential first-in-class antibiotic, a Strathclyde Minor Groove Binder (S-MGB), that has successfully completed Phase IIa clinical trials for the treatment of associated disease. Its precise mechanism of action and the origin of limited activity against Gram-negative pathogens are relatively unknown. Herein, treatment with MGB-BP-3 alone significantly inhibited the bacterial growth of the Gram-positive, but not Gram-negative, bacteria as expected.

"Just not knowing" can make life sweeter (and saltier): Reward uncertainty alters the sensory experience and consumption of palatable food and drinks.

Reward uncertainty can prompt exploration and learning, strengthening approach and consummatory behaviors. For humans, these phenomena are exploited in marketing promotions and gambling products, sometimes spurring hedonic consumption. Here, in four experiments, we sought to identify whether reward uncertainty-as a state of "not knowing" that exists between an action and a positively valanced outcome-enhances the in-the-moment consumption and experience of other palatable food and drink rewards.

A regioselectively 1,1',3,3'-tetrazincated ferrocene complex displaying core and peripheral reactivity.

Regioselective 1,1',3,3'-tetrazincation [C-H to C-Zn(Bu)] of ferrocene has been achieved by reaction of a fourfold excess of di--butylzinc (BuZn) with sodium 2,2,6,6-tetramethylpiperidide (NaTMP) in hexane solution manifested in the trimetallic iron-sodium-zinc complex [Na(TMP)Zn(Bu){(CH)Fe}], . X-ray crystallographic studies supported by DFT modelling reveal the structure to be an open inverse crown in which two [Na(TMP)Zn(Bu)Na(TMP)Zn(Bu)] cationic units surround a {(CH)Fe} tetraanion. Detailed CD NMR studies have assigned the plethora of H and C chemical shifts of this complex.

New reductive rearrangement of -arylindoles triggered by the Grubbs-Stoltz reagent EtSiH/KO Bu.

-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium butoxide. Studies indicate that the pathway involves (i) the formation of indole radical anions followed by fragmentation of the indole C2-N bond, and (ii) a ring-closing reaction that follows a potassium-ion dependent hydrogen atom transfer step. Unexpected behaviors of 'radical-trap' substrates prove very helpful in framing the proposed mechanism.

Bis(phosphine)hydridorhodacarborane Derivatives of 1,1'-Bis(-carborane) and Their Catalysis of Alkene Isomerization and the Hydrosilylation of Acetophenone.

Deprotonation of [7-(1'--1',2'-CBH)--7,8-CBH] and reaction with [Rh(PPh)Cl] results in isomerization of the metalated cage and the formation of [8-(1'--1',2'-CBH)-2-H-2,2-(PPh)--2,1,8-RhCBH] (). Similarly, deprotonation/metalation of [8'-(7--7,8-CBH)-2'-(-cymene)--2',1',8'-RuCBH] and [8'-(7--7,8-CBH)-2'-Cp*--2',1',8'-CoCBH] affords [8-{8'-2'-(-cymene)--2',1',8'-RuCBH}-2-H-2,2-(PPh)--2,1,8-RhCBH] () and [8-(8'-2'-Cp*--2',1',8'-CoCBH)-2-H-2,2-(PPh)--2,1,8-RhCBH] (), respectively, as diastereoisomeric mixtures. The performances of compounds - as catalysts in the isomerization of 1-hexene and in the hydrosilylation of acetophenone are compared with those of the known single-cage species [3-H-3,3-(PPh)--3,1,2-RhCBH] () and [2-H-2,2-(PPh)--2,1,12-RhCBH] (), the last two compounds also being the subjects of Rh NMR spectroscopic studies, the first such investigations of rhodacarboranes.

Investigation of the Factors That Dictate the Preferred Orientation of Lexitropsins in the Minor Groove of DNA.

Lexitropsins are small molecules that bind to the minor groove of DNA as antiparallel dimers in a specific orientation. These molecules have shown therapeutic potential in the treatment of several diseases; however, the development of these molecules to target particular genes requires revealing the factors that dictate their preferred orientation in the minor grooves, which to date have not been investigated. In this study, a distinct structure (thzC) was carefully designed as an analog of a well-characterized lexitropsin (thzA) to reveal the factors that dictate the preferred binding orientation.

Metabolomic Profiling of the Immune Stimulatory Effect of Eicosenoids on PMA-Differentiated THP-1 Cells.

Honey bee venom has been established to have significant effect in immunotherapy. In the present study, (Z)-11-eicosenol-a major constituent of bee venom, along with its derivations methyl cis-11-eicosenoate and cis-11-eicosenoic acid, were synthesised to investigate their immune stimulatory effect and possible use as vaccine adjuvants. Stimuli that prime and activate the immune system have exerted profound effects on immune cells, particularly macrophages; however, the effectiveness of bee venom constituents as immune stimulants has not yet been established.

Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components.

The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs.

Structural and Kinetic Profiling of Allosteric Modulation of Duplex DNA Induced by DNA-Binding Polyamide Analogues.

A combined structural and quantitative biophysical profile of the DNA binding affinity, kinetics and sequence-selectivity of hairpin polyamide analogues is described. DNA duplexes containing either target polyamide binding sites or mismatch sequences are immobilized on a microelectrode surface. Quantitation of the DNA binding profile of polyamides containing N-terminal 1-alkylimidazole (Im) units exhibit picomolar binding affinities for their target sequences, whereas 5-alkylthiazole (Nt) units are an order of magnitude lower (low nanomolar).

Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells.

Melittin, the major active peptide of honeybee venom (BV), has potential for use in adjuvant immunotherapy. The immune system response to different stimuli depends on the secretion of different metabolites from macrophages. One potent stimulus is lipopolysaccharide (LPS), a component isolated from gram-negative bacteria, which induces the secretion of pro-inflammatory cytokines in macrophage cell cultures.

Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL, and interleukin-12.

The possibility of using gene therapy for the treatment of prostate cancer is limited by the lack of intravenously administered delivery systems able to safely and selectively deliver therapeutic genes to tumors. Given that lactoferrin (Lf) receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of Lf to generation 3-diaminobutyric polypropylenimine dendrimer would improve its transfection and therapeutic efficacy in prostate cancer cells. In this study, we demonstrated that the intravenous administration of Lf-bearing DAB dendriplexes encoding TNFα resulted in the complete suppression of 70% of PC-3 and 50% of DU145 tumors over one month.

Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.

This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin polyamide incorporating an N-terminal imidazole (Im) unit. However, modification of the N-terminus from Im to Nt-building blocks results in an increase in dsDNA binding affinity but lower G-selectivity.

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells.

Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR (combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells.

Determination of the equilibrium constant of C fullerene binding with drug molecules.

We report a new analytical method that allows the determination of the magnitude of the equilibrium constant of complexation, K, of small molecules to C fullerene in aqueous solution. The developed method is based on the up-scaled model of C fullerene-ligand complexation and contains the full set of equations needed to fit titration datasets arising from different experimental methods (UV-Vis spectroscopy, H NMR spectroscopy, diffusion ordered NMR spectroscopy, DLS). The up-scaled model takes into consideration the specificity of C fullerene aggregation in aqueous solution and allows the highly dispersed nature of C fullerene cluster distribution to be accounted for.

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology.

In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.

Effect of Bee Venom and Its Fractions on the Release of Pro-Inflammatory Cytokines in PMA-Differentiated U937 Cells Co-Stimulated with LPS.

The venom of Apis mellifera (honey bee) has been reported to play a role in immunotherapy, but existing evidence to support its immuno-modulatory claims is insufficient. Four fractions from whole bee venom (BV) were separated using medium pressure liquid chromatography. Their ability to induce the production of cytokines TNFα, IL-1β and IL-6 in phorbol-12-myristate-13-acetate (PMA)-treated U937 cells was assessed.

Adding a Structural Context to the Deprotometalation and Trans-Metal Trapping Chemistry of Phenyl-Substituted Benzotriazole.

Organometallic bases are becoming increasingly complex, because mixing components can lead to bases superior to single-component bases. To better understand this superiority, it is useful to study metalated intermediate structures prior to quenching. This study is on 1-phenyl-1H-benzotriazole, which was previously deprotonated by an in situ ZnCl2 ⋅TMEDA/LiTMP (TMEDA=N,N,N',N'-tetramethylethylenediamine; TMP=2,2,6,6-tetramethylpiperidide) mixture and then iodinated.

(1)H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy.

Aim: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics.

Methods: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used.

Shape-independent model (SHIM) approach for studying aggregation by NMR diffusometry.

NMR diffusometry has been gaining wide popularity in various areas of applied chemistry for investigating diffusion and complexation processes in solid and aqueous phases. To date, the application of this method to study aggregation phenomena proceeding beyond the dimer stage of assembly has been restricted by the need for a priori knowledge of the aggregates' shape, commonly difficult to know in practice. We describe here a comprehensive analysis of aggregation parameter-dependency on the type and shape selected for modeling assembly processes, and report for the first time a shape-independent model (designated the SHIM approach), which may be used as an alternative in cases when information on aggregates' shapes is unavailable.

HOBS methods for enhancing resolution and sensitivity in small DNA oligonucleotide NMR studies.

(1) H NMR spectra from biopolymers give chemical shifts classified according to proton type and often suffer from signal degeneracy. Data from nucleic acids are particularly prone to this failing. Recent developments in proton broadband decoupling techniques with the promise of enhanced resolution at full sensitivity have allowed us to investigate the application of homonuclear band-selective (HOBS) decoupling to the study of small synthetic DNA molecules and to compare these with results from classical and pure shift techniques.

Effects of motives on reactions to safe sun messages.

We investigated whether appearance motive for sun exposure, which strongly predicts exposure behaviour, would predict reactions to safe sun messages. In a survey with an embedded experiment, 245 individuals completed measures of motives, read a safe sun message framed by incentive (appearance/health), tone (directive/nondirective) and valence (gain/loss), then completed measures of reactions. For participants high in appearance motive, an appearance-nondirective message was most persuasive.