Med25 Limits Master Regulators That Govern Adipogenesis

Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo phenotype by depleting lamins A and C (lamin A/C) in vitro. Although lamin A/C depletion elicits lipid accumulation, this effect appears to be mediated by divergent mechanisms dependent on the CM developmental state. To directly investigate Med25 in lipid accumulation, we induced adipogenesis in Med25-silenced 3T3-L1 preadipocytes and detected enhanced lipid accumulation. Assessment of pertinent mediators driving adipogenesis revealed that C/EBPα and PPARγ are super-induced by Med25 silencing. Our results indicate that Med25 limits adipogenic potential by suppressing the levels of master regulators that govern adipogenesis. Furthermore, we caution the use of early-developmental-stage cardiomyocytes to model adult-stage cells, particularly for dissecting metabolic perturbations emanating from LMNA mutations

Tuning the Interfacial Electronic Structure at Organic Heterojunctions by Chemical Design

Quantum-chemical techniques are applied to assess the electronic structure at donor/acceptor heterojunctions of interest for organic solar cells. We show that electrostatic effects at the interface of model 1D stacks profoundly modify the energy landscape explored by charge carriers in the photoconversion process and that these can be tuned by chemical design. When fullerene C₆₀ molecules are used as acceptors and unsubstituted oligothiophenes or pentacene are used as donors, the uncompensated quadrupolar electric field at the interface provides the driving force for splitting of the charge-transfer states into free charges. This quadrupolar field can be either enhanced by switching from a C₆₀ to a perylene-tetracarboxylic-dianhydride (PTCDA) acceptor or suppressed by grafting electron-withdrawing groups on the donor

Optical Properties of Oligothiophene Substituted Diketopyrrolopyrrole Derivatives in the Solid Phase: Joint J- and H‑Type Aggregation

Photophysical properties of diketopyrrolopyrrole derivatives substituted with oligothiophenes are investigated. All compounds are found to be fluorescent both in solution and in the solid phase. At low temperature in the solid, fluorescence originates from excimer-like excited states. Comparison of absorption and fluorescence excitation spectra taken under matrix isolated conditions and on solid films show the presence of both J- and H-type absorption bands in the solid phase. Quantum-chemical calculations, including exciton–phonon coupling to account for deviations from the Born–Oppenheimer approximation, are performed to simulate the band shape of the lowest absorption band in the molecular solid. The joint presence of J- and H-bands is explained by the presence of two molecules in the unit cell. The Davydov splitting is substantial for molecules with linear alkyl substituents on the nitrogen atom (on the order of 0.2 eV) but can be reduced to almost zero by introducing branching at the β-carbon of the alkyl side chain

Energetics of Electron–Hole Separation at P3HT/PCBM Heterojunctions

The energetics of electron–hole separation at the prototypical donor–acceptor interface P3HT/PCBM is investigated by means of a combination of molecular dynamics simulations, quantum-chemical methods, and classical microelectrostatic calculations. After validation against semiempirical Valence Bond/Hartree–Fock results, microelectrostatic calculations on a large number of electron–hole (e-h) pairs allowed a statistical study of charge separation energetics in realistic morphologies. Results show that charge separation is an energetically favorable process for about 50% of interfacial e-h pairs, which provides a rationale for the high internal quantum efficiencies reported for P3HT/PCBM heterojunctions. Three effects contribute to overcome the Coulomb attraction between electron and hole: (i) favorable electrostatic landscape across the interface, (ii) electronic polarization, and (iii) interface-induced torsional disorder in P3HT chains. Moreover, the energetic disorder due to the PCBM polar group is shown to play a key role in increasing the dissociation probability

Access to Urological Care for Medicaid-Insured Patients at Urology Practices Acquired by Private Equity Firms.

ObjectiveTo characterize appointment access for Medicaid-insured patients seeking care at urology practices affiliated with private equity firms in light of the recent national trends in practice consolidation.MethodsWe identified 214 urology offices affiliated with private equity firms that were geographically matched with 231 non-private equity affiliated urology offices. Using a standardized script, researchers posed as an adult patient with either Medicaid or commercial insurance in the clinical setting of new onset, painless hematuria. The primary outcome was whether the patient's insurance was accepted for an appointment. The secondary outcome was appointment wait time.ResultsWe conducted 815 appointment inquiry calls to 214 private equity (PE) and 231 non-PE-affiliated urology offices across 12 states. Appointment availability was higher for commercially-insured patients (99.0%; 95% CI: 98.1%-99.9%) vs Medicaid-insured patients (59.8%; 95% confidence interval [CI]: 55.0%-64.6%) (P < .0001). Medicaid acceptance was higher at non-PE affiliated (66.8%; CI 60.4%-73.2%) than PE-affiliated practices (52.1%; 95% CI 45.0%-59.2%) (P = .003). On multivariable logistic regression analysis, state Medicaid expansion status (odds ratio [OR] 2.20; CI 1.14-4.28; P = .020) was independently associated with Medicaid appointment availability, whereas PE-affiliation (OR 0.55; CI 0.37-0.83; P = .004) was independently associated with lower Medicaid access. Appointment wait times did not differ significantly for commercially-insured vs Medicaid patients (19.2 vs 20.1 days; p = .59), but PE-affiliated practices offered shorter mean wait times than non-PE offices (17.5 vs 21.4 days; P = .017).ConclusionAccess disparities for urologic evaluation in patients with Medicaid insurance at urology practices and were more pronounced at private equity acquired practices

Energetics of Electron\u2013Hole Separation at P3HT/PCBM Heterojunctions

The energetics of electronhole separation at the prototypical donor-acceptor interface P3HT/PCBM is investigated by means of a combination of molecular dynamics simulations, quantum-chemical methods, and classical microelectrostatic calculations. After validation against semiempirical Valence Bond/Hartree-Fock results, microelectrostatic calculations on a large number of electron-hole (e-h) pairs allowed a statistical study of charge separation energetics in realistic morphologies. Results show that charge separation is an energetically favorable process for about 50% of interfacial e-h pairs, which provides a rationale for the high internal quantum efficiencies reported for P3HT/PCBM heterojunctions. Three effects contribute to overcome the Coulomb attraction between electron and hole: (i) favorable electrostatic landscape across the interface, (ii) electronic polarization, and (iii) interface-induced torsional disorder in P3HT chains. Moreover, the energetic disorder due to the PCBM polar group is shown to play a key role in increasing the dissociation probability

Charge Dissociation at Interfaces between Discotic Liquid Crystals: The Surprising Role of Column Mismatch

The semiconducting and self-assembling properties of columnar discotic liquid crystals have stimulated intense research toward their application in organic solar cells, although with a rather disappointing outcome to date in terms of efficiencies. These failures call for a rational strategy to choose those molecular design features (e.g., lattice parameter, length and nature of peripheral chains) that could optimize solar cell performance. With this purpose, in this work we address for the first time the construction of a realistic planar heterojunction between a columnar donor and acceptor as well as a quantitative measurement of charge separation and recombination rates using state of the art computational techniques. In particular, choosing as a case study the interface between a perylene donor and a benzoperylene diimide acceptor, we attempt to answer the largely overlooked question of whether having well-matching donor and acceptor columns at the interface is really beneficial for optimal charge separation. Surprisingly, it turns out that achieving a system with contiguous columns is detrimental to the solar cell efficiency and that engineering the mismatch is the key to optimal performance