Bioorthogonal chemistries have provided tremendous insight into biomolecule structure and function. However, many popular bioorthogonal transformations are incompatible with one another, limiting ...their utility for studies of multiple biomolecules in tandem. We identified two reactions that can be used concurrently to tag biomolecules in complex environments: the inverse electron-demand Diels–Alder reaction of tetrazines with 1,3-disubstituted cyclopropenes, and the 1,3-dipolar cycloaddition of nitrile imines with 3,3-disubstituted cyclopropenes. Remarkably, the cyclopropenes used in these transformations differ by the placement of a single methyl group. Such orthogonally reactive scaffolds will bolster efforts to monitor multicomponent processes in cells and organisms.
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We systematically varied the degree of fluorination along the backbone of a series of highly regioregular 3-hexylthiophene-based polymers, P3HT-50F, P3HT-33F, and P3HT-25F, in which 50%, 33%, and ...25% of the thiophene units within the polymer chain contain fluorine atoms in the available 4-position, respectively. These materials were homopolymerized using the Kumada catalyst transfer polycondensation method from a set of mono-fluorinated bi-, ter-, and quarterthiophenes to ensure high polymer regioregularity and evenly spaced fluorine atoms along the conjugated thiophene backbone. The monomers were obtained from a synthetic route consisting of iterative Migita–Stille couplings of fluorinated and non-fluorinated 3-hexylthiophenes. The effect of the fluorine atoms on both polymer structure and properties is presented, with supporting quantum mechanical calculations that rationalize the intrinsic conformation preferences of the three P3HT derivatives. P3HT-50F (M̅ n = 34 kg/mol, 98.5% rr), P3HT-33F (M̅ n = 46 kg/mol, 98% rr), and P3HT-25F (M̅ n = 53 kg/mol, 95% rr) displayed HOMO levels of −5.34, −5.26, and −5.24 eV, bandgaps of 1.98, 1.98, and 1.97 eV, and average field-effect transistor hole mobilities of 4.5 × 10–3, 2.7 × 10–2, and 1.2 × 10–2 cm2 V–1 s–1, respectively.
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The Harvard organic photovoltaic dataset Lopez, Steven A; Pyzer-Knapp, Edward O; Simm, Gregor N ...
Scientific data,
09/2016, Volume:
3, Issue:
1
Journal Article
Peer reviewed
Open access
The Harvard Organic Photovoltaic Dataset (HOPV15) presented in this work is a collation of experimental photovoltaic data from the literature, and corresponding quantum-chemical calculations ...performed over a range of conformers, each with quantum chemical results using a variety of density functionals and basis sets. It is anticipated that this dataset will be of use in both relating electronic structure calculations to experimental observations through the generation of calibration schemes, as well as for the creation of new semi-empirical methods and the benchmarking of current and future model chemistries for organic electronic applications.
Silicon incorporation in polymethine dyes Pengshung, Monica; Neal, Patrick; Atallah, Timothy L ...
Chemical communications (Cambridge, England),
06/2020, Volume:
56, Issue:
45
Journal Article
Peer reviewed
Open access
Methods to red-shift fluorophores have garnered considerable interest due to the broad utility of low energy light. The incorporation of silicon into xanthene and coumarin scaffolds has resulted in ...an array of visible and near-infrared fluorophores. Here, we extend this approach to polymethine dyes, another popular fluorophore class, performing experimental and computational analyses. We found that when oxygen was replaced with SiMe
2
, bathochromic shifts of up to 121 nm and fluorophores with emission above 900 nm were achieved.
Incorporation of silicon into heterocycles for polymethine dyes can impart red-shifts of up to 100 nm, while also enhancing photostability up to 10-fold, resulting in photostable fluorophores with emission above 900 nm.
Inhibitors of the renin-angiotensin system are recommended for the management of albuminuria in patients with hypertension and diabetes mellitus, but there is little consensus about alternative ...therapies. Calcium channel blockers are recommended for the management of hypertension, but the data are controversial regarding their role in patients with albuminuria. This review was designed to assess the efficacy of calcium channel blockers compared with inhibitors of the renin-angiotensin system in decreasing albuminuria in diabetic, hypertensive patients with nephropathy.
We searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for records that compared calcium channel blockers to inhibitors of the renin-angiotensin system and reported pre- and postintervention albuminuria measurements. Two reviewers independently screened abstracts for randomized, controlled trials in adults. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select 29 trials from 855 records. We synthesized the data through a random-effects model.
We analyzed data from 2113 trial participants with hypertension and diabetes mellitus who had the equivalent of ≥30 mg/day of urinary albumin excretion. Inhibitors of the renin-angiotensin system were more effective than calcium channel blockers in decreasing albuminuria (standardized difference in means −0.442; confidence interval, −0.660 to −0.225; P < .001). This finding was independent of the blood pressure response to treatment. There was no difference between the 2 drug classes regarding markers of renal function.
Inhibitors of the renin-angiotensin system are superior to calcium channel blockers for the reduction of albuminuria in nephropathy due to hypertension and diabetes mellitus. The net clinical benefit, however, is small.
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) ...remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.
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•Time course analysis of HLA-I immunopeptidome in SARS-CoV-2-infected cells•25% of detected HLA-I peptides originated from out-of-frame ORFs in S and N•Some out-of-frame peptides elicited stronger T cell responses than canonical peptides•Early expressed viral proteins dominated HLA-I presentation and immunogenicity
Analysis of the HLA-I peptidome of SARS-CoV-2 infection identifies peptides derived from canonical and out-of-frame ORFs in viral S and N protein that are not captured by current vaccines and yield potent T cell responses in a mouse model as well as individuals with COVID-19.
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Nanothreads are emerging one-dimensional sp3-hybridized materials with high predicted tensile strength and a tunable band gap. They can be synthesized by compressing aromatic or nonaromatic small ...molecules to pressures ranging from 15–30 GPa. Recently, new avenues are being sought that reduce the pressure required to afford nanothreads; the focus has been placed on the polymerization of molecules with reduced aromaticity, favorable stacking, and/or the use of higher reaction temperatures. Herein, we report the photochemically mediated polymerization of pyridine and furan aromatic precursors, which achieves nanothread formation at reduced pressures. In the case of pyridine, it was found that a combination of slow compression/decompression with broadband UV light exposure yielded a crystalline product featuring a six-fold diffraction pattern with similar interplanar spacings to previously synthesized pyridine-derived nanothreads at a reduced pressure. When furan is compressed to 8 GPa and exposed to broadband UV light, a crystalline solid is recovered that similarly demonstrates X-ray diffraction with an interplanar spacing akin to that of the high-pressure synthesized furan-derived nanothreads. Our method realizes a 1.9-fold reduction in the maximum pressure required to afford furan-derived nanothreads and a 1.4-fold reduction in pressure required for pyridine-derived nanothreads. Density functional theory and multiconfigurational wavefunction-based computations were used to understand the photochemical activation of furan and subsequent cascade thermal cycloadditions. The reduction of the onset pressure is caused by an initial 4+4 cycloaddition followed by increasingly facile thermal 4+2-cycloadditions during polymerization.
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Xanthommatin (Xa) is a naturally occurring broad-spectrum dye present in arthropods and cephalopods. In these animals, Xa is enzymatically produced via the oxidative cyclization of ...3-hydroxykynurenine (3-OHK), a metabolite of tryptophan, but it can also be synthesized in vitro using an iron-based oxidizing agent. While the optoelectronic properties (e.g., high refractive index, redox-sensitive color) of both natural and synthetic forms of Xa have inspired its use in materials, its synthesis faces challenges, in terms of both scalability and purity. We describe a procedure to synthesize Xa via electrochemical oxidation of 3-OHK, which offers both economic and ecological advantages over the traditional method. We used density functional theory calculations to describe the kinetics and thermodynamics of the cyclization of Xa based on the loss of eight electrons and protons from 2 molar equiv of 3-OHK. Our results provide insight into the production of this biochrome in a process that can be scaled up for future materials applications and/or adapted to the production of other phenoxazinones synthesized from ortho-aminophenols.
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OBJECTIVES:Reversing HIV-1 latency has been suggested as a strategy to eradicate HIV-1. We investigated the effect of romidepsin on the HIV transcription profile in participants from the REDUC part B ...clinical trial.
DESIGN:Seventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of the therapeutic vaccine Vacc-4x followed by treatment with three doses of romidepsin. Samples from nine study participants were available for HIV transcription profile analysis.
METHODS:Read-through, total (TAR), elongated (longLTR), polyadenylated (polyA) and multiply-spliced (Tat-Rev) HIV transcripts and total HIV DNA were quantified at baseline (visit 1) and 4 h after the second (visit 10b) and third (visit 11b) romidepsin infusions.
RESULTS:Read-through, total, elongated, and polyadenylated HIV transcripts increased after romidepsin infusion (P = 0.020, P = 0.0078, P = 0.0039, P = 0.027, respectively), but no changes were observed in multiply-spliced HIV RNA or HIV DNA. No change was observed in the ratio of read-through/total HIV transcripts. The ratio of elongated/total HIV RNA increased after romidepsin (P = 0.016), whereas the ratio of polyadenylated/elongated HIV decreased. Both elongated HIV transcripts and total HIV DNA correlated negatively with the time to viral rebound after interruption of ART.
CONCLUSIONS:In these patients, romidepsin increased early events in HIV transcription (initiation and especially elongation), but had less effect on later stages (completion, multiple splicing) that may be required for comprehensive latency reversal and cell killing. Without cell death, increased HIV transcription before or after latency reversal may hasten viral rebound after therapy interruption.
Theory suggests evolutionary change can significantly influence and act in tandem with ecological forces via ecological-evolutionary feedbacks. This theory assumes that significant evolutionary ...change occurs over ecologically relevant timescales and that phenotypes have differential effects on the environment. Here we test the hypothesis that local adaptation causes ecosystem structure and function to diverge. We demonstrate that populations of Trinidadian guppies (Poecilia reticulata), characterized by differences in phenotypic and population-level traits, differ in their impact on ecosystem properties. We report results from a replicated, common garden mesocosm experiment and show that differences between guppy phenotypes result in the divergence of ecosystem structure (algal, invertebrate, and detrital standing stocks) and function (gross primary productivity, leaf decomposition rates, and nutrient flux). These phenotypic effects are further modified by effects of guppy density. We evaluated the generality of these effects by replicating the experiment using guppies derived from two independent origins of the phenotype. Finally, we tested the ability of multiple guppy traits to explain observed differences in the mesocosms. Our findings demonstrate that evolution can significantly affect both ecosystem structure and function. The ecosystem differences reported here are consistent with patterns observed across natural streams and argue that guppies play a significant role in shaping these ecosystems.
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