A non-symmetrical p97 conformation initiates a multistep recruitment of Ufd1/Npl4.

experiments and cryo-EM structures of p97 and its cofactor, Ufd1/Npl4 (UN), elucidated substrate processing. Yet, the structural transitions and the related ATPase cycle upon UN binding remain unresolved. We captured two discrete conformations: One in which D1 protomers are ATP bound, while the D2 subunits are in the ADP state, presumably required for substrate engagement with the D2 pore; and a heterologous nucleotide state within the D1 ring in which only two NTDs are in the "up" ATP state that favors UN binding.

Noninvasive Real-Time Glucose Monitoring Is in the Near Future.

Since the introduction of continuous glucose monitoring (CGM) technology, developers have rigorously researched the feasibility of creating a noninvasive glucose monitoring device. In a recent pilot study, investigators reported a strong correlation between glucose values obtained from novel noninvasive monitoring device (GWave) values to venous and capillary glucose measurements. We investigated whether the level of accuracy observed in the pilot study could be reproduced in a larger cohort, using a smaller third-generation manufacturable device (Gen III GWave) containing a standardized sensor chip that can be mass produced for commercial use.

Death spiral of the legacy grid: A game-theoretic analysis of modern grid defection processes.

Decreasing costs of distributed generation and storage, alongside increasing network charges, provide consumers with a growing incentive to defect from the main grid. On a large scale, this may lead to price inflation, hindrance of the energy transition, and even a "death spiral" - a domino effect of disconnections. Here, we develop a game-theoretic framework that demonstrates how conflicting interests among consumers - an aspect that previous studies overlooked - may lead to complex dynamics of grid defection.

The role of RNF149 in the pre-emptive quality control substrate ubiquitination.

Protein quality control is a process in which a protein's folding status is constantly monitored. Mislocalized proteins (MLP), are processed by the various quality control pathways, as they are often misfolded due to inappropriate cellular surroundings. Polypeptides that fail to translocate into the ER due to an inefficient signal peptide, mutations or ER stress are recognized by the pre-emptive ER associated quality control (pEQC) pathway and degraded by the 26 S proteasome.

Germline genetic biomarkers to stratify patients for personalized radiation treatment.

Background: Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes.