Structural differences between the SH3-HOOK-GuK domains of SAP90/PSD-95 and SAP97

The SH3-HOOK-GUK domains of the postsynaptic scaffolding proteins SAP90/PSD-95 and SAP97 are established targets of synaptic plasticity processes in the brain. A crucial molecular mechanism involved is the transition of this domain to different conformational states. We purified the SH3-HOOK-GUK domain of both proteins to examine variations in protein conformation and stability. As monitored by circular dichroism and differential scanning calorimetry, SAP97 (T_m = 64 °C) is significantly more thermal stable than SAP90/PSD-95 (T_m = 52 °C) and follows a bimodal phase transition. GdmCl-induced equilibrium unfolding of both proteins follows the two-state transitions and thus does not involve the accumulation of stable intermediate state(s). Equilibrium unfolding of SAP97 is highly cooperative from a native state to an unfolded state. In contrast, SAP90/PSD-95 follows a non-cooperative transition from native to unfolded states. A highly cooperative unfolding reaction in case of SAP97 indicates that the protein existed initially as a compact, well-folded structure, while the gradual, non-cooperative melting reaction in case of SAP90/PSD-95 indicates that the protein is in comparison more flexible.     

Interface Engineering Driven Stabilization of Halide Perovskites against Moisture,Heat, and Light for Optoelectronic Applications

Moisture, heat, and light instabilities of halide perovskites (HPs) represent a serious Achilles' heel that must be overcome, to enable future advancements in perovskite‐based optoelectronic devices such as solar cells and light‐emitting diodes. The instabilities are attributed to the unavoidable fragile ionic bonding between cationic and anionic parts of HPs during their formation. Surface passivation of HPs by various surface‐passivating materials has proven to be an attractive approach to stabilize perovskites against moisture, heat, and light, keeping intact their structural integrity and ionic bonding. Herein, the experimental and theoretical background for degradation mechanisms of HPs is reviewed along with various surface passivating materials to stabilize HPs. Finally, the existing challenges associated with thin‐film and device fabrication and an outlook for improving the stability of perovskites in optoelectronics are presented     

Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway

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Limited Invasive Protocol: Optimizing Diagnostic Modalities in Corticotropin Mediated Cushing Syndrome

BackgroundTo limit the role of bilateral inferior petrosal sinus sampling (BIPSS) in distinguishing between Cushing disease (CD) and ectopic Cushing syndrome (ECS), recent reports have proposed a noninvasive approach based on a combination of biochemical testing and radiological imaging as an alternative to the conventional invasive strategy (CIS). However, this strategy requires further validation. The current study aimed to evaluate 2 limited invasive protocols (LIP-1 and LIP-2) in limiting the role of BIPSS while maintaining a diagnostic accuracy similar to that of CIS.MethodsThis was a single-center study conducted on individuals with corticotropin-dependent Cushing syndrome. The LIPs were based on performing high-dose dexamethasone suppression (>50% cut-off in first [LIP-1] and >80% in second [LIP-2]) and magnetic resonance imaging of the sella in all individuals and selective use of computed tomography of the chest and abdomen before BIPSS. These LIPs were evaluated for limiting the use of BIPSS, their accuracy, and cost in comparison to CIS.ResultsOf the 206 individuals, 114 (97 of CD and 21 of ECS) were eligible for the current study. Using LIP-1, LIP-2, and CIS, BIPSS could have been avoided in 62.3%, 35.9%, and 25.4% of individuals, respectively. The positive predictive value for CD using LIP-1 and LIP-2 was 98.9% and 100%, respectively. The cost per patient evaluated using LIP-1, LIP-2, and CIS was $602.21, $966.81, and $1107.78, respectively.ConclusionLIPs represent an equally accurate, less invasive, and more cost-effective alternative to the CIS for distinguishing between CD and ECS.