A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo incorporation of aryl ketone functionality into proteins

Incorporation of non-natural amino acids into proteins in vivo expands the scope of protein synthesis and design. p-Acetylphenylalanine was incorporated into recombinant dihydrofolate reductase (DHFR) in Escherichia coli via a computationally designed mutant form of the phenylalanyl-tRNA synthetase of the host. DHFR outfitted with ketone functionality can be chemoselectively ligated with hydrazide reagents under mild conditions

Derivatives of 8-Hydroxy-2-methylquinoline Are Powerful Prototypes for Zinc Sensors in Biological Systems

The recent emphasis on understanding the myriad roles of zinc in both normal and diseased cells and tissues has placed an ever increasing demand on methods for sensitive and selective methods for real-time monitoring of free Zn^(2+) in complex biological samples. Chelation-enhanced fluorescent sensors for zinc, based on fluorophores such as quinoline, dansyl, fluorescein, and anthracene, have been reported. While each of these agents has unique advantages, there remain issues with sensitivity, selectivity, and specificity that may be addressable with an alternate chromophore that is readily amenable to synthetic manipulation. Herein we report the systematic chemical modification of the 8-hydroxy-2-methylquinoline (Oxn) unit as a building block for the development of new sensors employing chelation-enhanced fluorescence. In particular, improvements in quantum yield from 0.004 to 0.70 and stepwise blue shifts in fluorescence emission wavelengths (to a total of over 70 nm) are reported

Water activity and activation diameters from hygroscopicity data - Part I: Theory and application to inorganic salts

International audienceA method is described that uses particle hygroscopicity measurements, made with a humidified tandem differential mobility analyzer (HTDMA), to determine solution water activity as a function of composition. The use of derived water activity data in computations determining the ability of aerosols to serve as cloud condensation nuclei (CCN) is explored. Results for sodium chloride and ammonium sulfate are shown in Part I. The methodology yields solution water activities and critical dry diameters for ammonium sulfate and sodium chloride in good agreement with previously published data. The approach avoids the assumptions required for application of simplified and modified Köhler equations to predict CCN activity, most importantly, knowledge of the molecular weight and the degree of dissociation of the soluble species. Predictions of the dependence of water activity on the mass fraction of aerosol species are sensitive to the assumed dry density, but predicted critical dry diameters are not

The Population Affected by the Syndemic of COVID-19 and Poverty is More Likely to be Hospitalized with SARS-CoV-2 Pneumonia

Background Lockdown measures to control COVID-19 have exacerbated the poverty epidemic. We hypothesized that the synergistic interaction of COVID-19 and poverty epidemics favors the development of more severe forms of COVID-19 in the population living in poverty. To test this hypothesis, we assessed whether an ecological association exists between the geographic distribution of hospitalized patients with SARS-CoV-2 pneumonia and markers of poverty in the city of Louisville, KY. Methods Using the geomasked home addresses of hospitalized patients with SARS-CoV-2 pneumonia in the city of Louisville, a kernel density heatmap was created. Kuldorff’s spatial scan statistic was used to calculate areas of increased risk for SARS-CoV-2 pneumonia hospitalization. Heat maps were created for census tract–level demographics according to income, age, race, and ethnicity to assess whether an ecological association exists with the spatial distribution of SARS-CoV-2 pneumonia hospitalization. Results Four areas of increased risk of hospitalization due to SARS-CoV-2 pneumonia were identified in the western and central sections of the city, with relative risks (RRs) ranging from 2.3 to 3.2 (p Conclusions Residents from low-income areas are almost three times more likely to develop SARS-CoV-2 pneumonia requiring hospitalization. Current efforts to decrease the number of COVID-19 hospitalizations through vaccination of populations at risk should be concentrated in city areas with a low-income level population

Water activity and activation diameters from hygroscopicity data - Part II: Application to organic species

International audienceA method has been developed for using particle hygroscopicity measurements made with a humidified tandem differential mobility analyzer (HTDMA) to determine water activity as a function of solute weight percent. In Part I, the method was tested for particles composed of sodium chloride and ammonium sulfate. Here, we report results for several atmospherically-relevant organic species: glutaric acid, malonic acid, oxalic acid and levoglucosan. Predicted water activities for aqueous dicarboxylic acid solutions are quite similar in some cases to published estimates and the simplified predictions of Köhler theory, while in other cases substantial differences are found, which we attribute primarily to the semivolatile nature of these compounds that makes them difficult to study with the HTDMA. In contrast, estimates of water activity for levoglucosan solutions compare very well with recently-reported measurements and with published data for aqueous glucose and fructose solutions. For all studied species, the critical dry diameters active at supersaturations between 0.2 and 1% that are computed with the HTDMA-derived water activities are generally within the experimental error (~20%) estimated in previously-published direct measurements using cloud condensation nuclei counters. For individual compounds, the variations in reported solution water activity lead to uncertainties in critical dry diameters of 5-25%, not significantly larger than the uncertainty in the direct measurements. To explore the impact of these uncertainties on modeled aerosol-cloud interactions, we incorporate the variations in estimates of solution water activities into the description of hygroscopic growth of aerosol particles in an adiabatic parcel model and examine the impact on the predicted drop number concentrations. For the limited set of initial conditions examined here, we find that the uncertainties in critical dry diameters for individual species lead to 0-21% changes in drop number concentration, with the largest effects at high aerosol number concentrations and slow updraft velocities. Ammonium sulfate, malonic acid and glutaric acid have similar activation behavior, while glutaric acid and levoglucosan are somewhat less hygroscopic and lead to lower drop number concentrations; sodium chloride is the most easily activated compound. We explain these behaviors in terms of a parameter that represents compound hygroscopicity, and conclude that this parameter must vary by more than a factor of 2 to induce more than a 15% change in activated drop number concentrations. In agreement with earlier studies, our results suggest that the number concentration of activated drops is more sensitive to changes in the input aerosol size and number concentrations and the applied updraft velocity than to modest changes in the aerosol composition and hygroscopic properties

Lithographic Patterning of Photoreactive Cell-Adhesive Proteins

We describe a novel, simple method for the photolithographic patterning of cell-adhesive proteins. Intrinsically photoreactive proteins are synthesized in Escherichia coli through incorporation of the non-canonical, photosensitive amino acid para-azidophenylalanine. Upon ultraviolet irradiation at 365 nm, proteins form cross-linked films with elastic moduli that can be tuned by varying the concentration of photoreactive amino acid in the expression medium. Films of these proteins can be directly patterned using standard photolithographic techniques. We demonstrate the utility of this method of protein patterning by creating stable arrays of fibroblast cells on an engineered protein “photoresist”

Lack of Association of the ABO Blood Group with COVID-19 risk and Severity in Hospitalized Patients in Louisville, KY

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity. Methods: This was a retrospective observational study of 380 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients were divided into four different groups according to their ABO blood type. Demographic characteristics and clinical variables, including laboratory data as well as clinical outcomes were compared. Results: Type O was the most common blood group among the hospitalized patients (51%) followed by type A (31%), B (14%) and AB (4%). The observed blood group distribution among the patients was not significantly different from the distribution expected when compared to a population of similar racial/ethnic composition. No significant associations were found between the blood group and comorbidities, inflammatory biomarkers as well as with recorded outcomes, including the mortality rate and the length of the hospital stay. Conclusions: The data from hospitalized patients in Louisville is is not consistent with the ABO blood group having a significant effect as a risk or severity factor for COVID-19, but it is representative in COVID-19 or its severityof its prevalence among different racial/ethnic populations