Evaluating the impact of ultraviolet C exposure conditions on coliphage MS2 inactivation on surfaces.

The COVID-19 pandemic has raised interest in using devices that generate ultraviolet C (UVC) radiation as an alternative approach for reducing or eliminating microorganisms on surfaces. Studies investigating the efficacy of UVC radiation against pathogens use a wide range of laboratory methods and experimental conditions that can make cross-comparison of results and extrapolation of findings to real-world settings difficult. Here, we use three different UVC-generating sources - a broad-spectrum pulsed xenon light, a continuous light-emitting diode (LED), and a low-pressure mercury vapour lamp - to evaluate the impact of different experimental conditions on UVC efficacy against the coliphage MS2 on surfaces. We find that a nonlinear dose-response relationship exists for all three light sources, meaning that linear extrapolation of doses resulting in a 1-log10 (90%) reduction does not accurately predict the dose required for higher (e.g. 3-log10 or 99.9%) log10 reductions. In addition, our results show that the inoculum characteristics and underlying substrate play an important role in determining UVC efficacy. Variations in microscopic surface topography may shield MS2 from UVC radiation to different degrees, which impacts UVC device efficacy. These findings are important to consider in comparing results from different UVC studies and in estimating device performance in field conditions.

Inactivation of MS2 bacteriophage on copper film deployed in high touch areas of a public transport system.

Although SARS-CoV-2 is primarily an airborne risk, the COVID-19 pandemic also highlighted the need for self-disinfection surfaces that could withstand the demand of high occupant densities characteristic of public transportation systems. The aim of this study was to evaluate the durability and antiviral activity of a copper film deployed for 90 days in two high touch locations within an active metropolitan bus and railcar. The antiviral efficacy of this copper film after being deployed in transit vehicles for 90 days (deployed copper film) was then compared to new (unused) copper film to determine if frequent touches and cleaning protocols could decrease the efficacy of the copper films. Deployed copper film, new copper film, and aluminium foil (positive control) coupons were inoculated with ~1 × 106 MS2 virus particles, allowed a contact time of either 5- or 10-min, and analysed for residual viral infectiousness. On both new and deployed copper films, MS2 was completely inactivated (≥5 log reduction) at both time points. These results suggest that the copper film may provide the durability demanded by high touch public spaces while maintaining the antiviral activity necessary to reduce exposure risk and viral transmission via surfaces in public transportation settings.

Sex differences in motivations for and effects of drinking among college students.

A sample of college students (70 men and 70 women, each group composed of equal numbers of heavy and light drinkers) completed the Beck Depression Inventory, Form V of the Sensation Seeking Scale, the S-R Inventory of General Trait Anxiousness, the Rosenberg Self-Esteem Scale, as well as seven other measures directly assessing alcohol-related attitudes and behavior. It was hypothesized that heavy drinkers would evidence strong sensation-seeking needs with a specially high need for disinhibition. It was also predicted that heavy-drinking women would display more adjustment problems than other students and would report greater anxiety than men when drinking in situations involving social evaluation or interactions with members of the opposite sex. The first hypothesis was confirmed: heavy drinkers did exhibit strong sensation-seeking needs. However, heavy-drinking women were not characterized by adjustment problems nor did they report greater anxiety in drinking situations. The results suggest that women tend to drink to enhance social pleasures, whereas men expect a greater degree of aggressive arousal and social deviance when drinking.

Using self report measures to corroborate theories of depression: the specificity problem.

Depression scales tend to correlate highly with measures of anxiety and other negative emotional states. If the same is true of scales measuring constructs from depression theories such as negative cognitions and anaclitic depression, it brings into question the specificity of these models to depression. The overlap has been attributed to the common role of negative affect in depression and anxiety. Using a sample of college students, our study investigated the relationships among measures of depression, anxiety, positive and negative affect, and theory-relevant constructs. Theory-relevant scales related no more strongly to depression than anxiety measures. Furthermore, they related strongly either with negative or positive affect but usually not with both. These findings bring into question the specificity of depression models corroborated through the available self-report measures.

Active unfolding of precursor proteins during mitochondrial protein import.

Precursor proteins made in the cytoplasm must be in an unfolded conformation during import into mitochondria. Some precursor proteins have tightly folded domains but are imported faster than they unfold spontaneously, implying that mitochondria can unfold proteins. We measured the import rates of artificial precursors containing presequences of varying length fused to either mouse dihydrofolate reductase or bacterial barnase, and found that unfolding of a precursor at the mitochondrial surface is dramatically accelerated when its presequence is long enough to span both membranes and to interact with mhsp70 in the mitochondrial matrix. If the presequence is too short, import is slow but can be strongly accelerated by urea-induced unfolding, suggesting that import of these 'short' precursors is limited by spontaneous unfolding at the mitochondrial surface. With precursors that have sufficiently long presequences, unfolding by the inner membrane import machinery can be orders of magnitude faster than spontaneous unfolding, suggesting that mhsp70 can act as an ATP-driven force-generating motor during protein import.

Differential biological effects of K252 kinase inhibitors are related to membrane solubility but not to permeability.

K252a and K252b are related protein kinase inhibitors that, dependent on conditions, can either inhibit or potentiate the effects of neurotrophic factors. K252a, an ester, is more potent and more cytotoxic on intact cells than K252b, a carboxylic acid. To understand better why these drugs elicit different degrees of biological responses, we analyzed their hydrophobicity, cell permeability, and subcellular distribution. As judged by partitioning between organic and aqueous phases, both compounds are hydrophobic. The partition coefficients were 15.6:1 (organic/aqueous phases) for K252a and 4.4:1 for K252b. The ratio of fluorescence excitation at 352 nm to that at 340 nm for the K252 compounds in the organic alcohol 1-decanol versus water provides a simple assay of binding of these compounds to phospholipid membranes. This ratio shifted for K252a, but not K252b, in the presence of phospholipid vesicles, indicating that K252a dissolved in the hydrophobic interior of the membrane. Using quantitative video fluorescence microscopy, we found that K252a strongly labeled both Sf9 insect cells and PC12 rat pheochromocytoma cells, probably staining intracellular membranes. The uptake of K252a was rapid and apparently irreversible. K252b also quickly entered Sf9 and PC12 cells, but staining was much weaker. Hence, K252a and K252b are similar in that they both rapidly enter cells but greatly differ in their membrane solubility.

Mitochondria unfold precursor proteins by unraveling them from their N-termini.

Protein unfolding is a key step in the life cycle of many proteins, including certain proteins that are degraded by ATP-dependent proteases or translocated across membranes. The detailed mechanisms of these unfolding processes are not understood. Precursor proteins are unfolded and imported into mitochondria by a macromolecular machine that spans two membranes and contains at least nine different proteins. Here we examine import of a model precursor protein derived from the ribonuclease barnase and show that mitochondria unfold this protein by unraveling it from its N-terminus. Because barnase in free-solution unfolds by a different pathway, our results demonstrate that mitochondria catalyze unfolding in the way that enzymes catalyze reactions, namely by changing reaction pathways. The effectiveness of this mechanism depends on the structure of the N-terminal part of the precursor protein.