E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.

FragPT2: Multifragment Wave Function Embedding with Perturbative Interactions.

Embedding techniques allow the efficient description of correlations within localized fragments of large molecular systems while accounting for their environment at a lower level of theory. We introduce FragPT2: a novel embedding framework that addresses multiple interacting active fragments. Fragments are assigned separate active spaces, constructed by localizing canonical molecular orbitals.

Effect of Divalent Cations on Polarity and Hydration at the Lipid/Water Interface Probed by 4-Aminophthalimide-Based Dyes.

The ion binding to the lipid/water interface can substantially influence the structural, functional, and dynamic properties of the cell membrane. Despite extensive research on ion-lipid interactions, the specific effects of ion binding on the polarity and hydration at the lipid/water interface remain poorly understood. This study explores the influence of three biologically relevant divalent cations─Mg, Ca, and Zn─on the depth-dependent interfacial polarity and hydration of zwitterionic DPPC lipid in its gel phase at room temperature.

Benchmark computations of nearly degenerate singlet and triplet states of N-heterocyclic chromophores. II. Density-based methods.

In this paper, we demonstrate the performance of several density-based methods in predicting the inversion of S1 and T1 states of a few N-heterocyclic triangulene based fused ring molecules (popularly known as INVEST molecules) with an eye to identify a well performing but cost-effective preliminary screening method. Both conventional linear-response time-dependent density functional theory (LR-TDDFT) and ΔSCF methods (namely maximum overlap method, square-gradient minimization method, and restricted open-shell Kohn-Sham) are considered for excited state computations using exchange-correlation (XC) functionals from different rungs of Jacob's ladder. A well-justified systematism is observed in the performance of the functionals when compared against fully internally contracted multireference configuration interaction singles and doubles and/or equation of motion coupled-cluster singles and doubles (EOM-CCSD), with the most important feature being the capture of spin-polarization in the presence of correlation.

Comparative Analysis of Patient-Reported Outcome Measures in Manual Small-Incision Cataract Surgery Versus Phacoemulsification for Brown Cataracts.

Objective The objective of this study is to compare patient-reported outcome measures using the Catquest Questionnaire in patients undergoing phacoemulsification (Phaco) versus manual small-incision cataract surgery (MSICS). Materials and methods This descriptive cross-sectional study included patients aged 40 years and older with cataracts classified as nuclear sclerosis (NS) grade 3 or higher. Demographic details were recorded and a comprehensive ophthalmological exam was done.