Sulfamyl Radicals Direct Photoredox-Mediated Giese Reactions at Unactivated C(3)–H Bonds

This manuscript describes the use of alcohol-derived sulfamate ester anchors to guide the alkylation of aliphatic C(3)–H bonds in the course of Giese reactions. This reaction tolerates a large range of functional groups that are sensitive to oxidation. The developed reaction proceeds with predictable diastereoselectivity using enantioenriched radical acceptors, and complex small molecule substrates. Surprisingly, this transformation affects position-selective alkylation of tertiary and secondary centers with synthetically useful efficiencies

Photochemically-Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides

A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverates a dual-catalytic system of nickel and a photoexcitable iridium complex and proceeds at room temperature under visible light irradiation. Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. Thereby, this method complements known Buchwald-Hartwig coupling methods for N-arylation of sulfamides

Raising awareness of chronic measurement error intrinsic to immunoassay measurements of small molecule analytes.

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The effect of specific binding proteins on immunoassay measurements of total and free thyroid hormones and cortisol.

Background: Immunoassay (IA) measurements of thyroid hormones have previously given inaccurate results of triiodothyronine (T3), free triiodothyronine (FT3), and free thyroxine (FT4) when concentrations of TBG are low. We evaluate the hypothesis that abnormal concentrations of specific binding proteins (BPs) affect IA measurements and provide results which might misguide the diagnosis and treatment of patients. This study assesses IAs for the measurement of T3, FT3, and cortisol when levels of TBG and CBG are high or low. Comparisons are made between IA and LC-MS/MS. Methods: Serum or plasma samples with high (\u3e95th percentile, Results: When TBG levels are \u3c5th \u3epercentile, the differences between the IA and LC-MS/MS results for T3 and FT3 are statistically significant (T3, Conclusion: Abnormal BP concentrations appear to affect the accuracy of IA measurements of T3, FT3, and cortisol. The population of patients with either high or low levels of BPs is significant. Our samples reflect that 65% of women aged between 15 and 49 years are taking oral contraceptives in the US, and thus have elevated levels of BPs. In this group, IA results for cortisol are falsely low. Our samples reflect that patients with protein losing diseases have low BP concentrations. Among a group with renal complications, IA measurements of T3 are overestimated, while those of FT3 are underestimated. Are the Food and Drug Administration and diagnostic companies adequately assessing the accuracy of IA tests

A Shift to Human Body Temperature (37°C) Rapidly Reprograms Multiple Adaptive Responses in \u3ci\u3eEscherichia coli\u3c/i\u3e That Would Facilitate Niche Survival and Colonization

One of the first environmental cues sensed by a microbe as it enters a human host is an upshift in temperature to 37°C. In this dynamic time point analysis, we demonstrate that this environmental transition rapidly signals a multitude of gene expression changes in Escherichia coli. Bacteria grown at 23°C under aerobic conditions were shifted to 37°C, and mRNA expression was measured at time points after the shift to 37°C (t = 0.5, 1, and 4 h). The first hour is characterized by a transient shift to anaerobic respiration strategies and stress responses, particularly acid resistance, indicating that temperature serves as a sentinel cue to predict and prepare for various niches within the host. The temperature effects on a subset of stress response genes were shown to be mediated by RpoS and directly correlated with RpoS, DsrA, and RprA levels, and increased acid resistance was observed that was dependent on 23°C growth and RpoS. By 4 h, gene expression shifted to aerobic respiration pathways and decreased stress responses, coupled with increases in genes associated with biosynthesis (amino acid and nucleotides), iron uptake, and host defense. ompT, a gene that confers resistance to antimicrobial peptides, was highly thermoregulated, with a pattern conserved in enteropathogenic and uropathogenic E. coli strains. An immediate decrease in curli gene expression concomitant with an increase in flagellar gene expression implicates temperature in this developmental decision. Together, our studies demonstrate that temperature signals a reprogramming of gene expression immediately upon an upshift that may predict, prepare, and benefit the survival of the bacterium within the host