Regulation of the phd/doc toxin-antitoxin operon involves the toxin Doc as co- or derepressor depending on the ratio between Phd and Doc, a phenomenon known as conditional cooperativity. The mechanism underlying this observed behavior is not understood. Here we show that monomeric Doc engages two Phd dimers on two unrelated binding sites. The binding of Doc to the intrinsically disordered C-terminal domain of Phd structures its N-terminal DNA-binding domain, illustrating allosteric coupling between highly disordered and highly unstable domains. This allosteric effect also couples Doc neutralization to the conditional regulation of transcription. In this way, higher levels of Doc tighten repression up to a point where the accumulation of toxin triggers the production of Phd to counteract its action. Our experiments provide the basis for understanding the mechanism of conditional cooperative regulation of transcription typical of toxin-antitoxin modules. This model may be applicable for the regulation of other biological systems.
Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma.
Desmin and Vimentin are major intermediate filaments at the Z-disc and play significant roles in sarcomere architecture and signaling transduction. Abnormal expression of sarcomeric Desmin and Vimentin (SDV) results in severe dysfunctions of striated muscles. In this study, it was found that paired Numb family proteins (NFPs), including Numb and its homolog Numblike, determined the range for the recruitment of SDV to the primitive Z-disc.
Background: Intake of branched-chain amino acids (BCAA) has been suggested to have a prophylactic effect against carcinogenesis in colorectal cancer (CRC). However, the possible effect of plasma BCAA concentration has not been fully evaluated.
Methods: We conducted a prospective case-control study within a cohort of four public health center areas for which blood sample and questionnaire data from a 5-year follow-up survey were available.
Objectives: In conditional automation for automated vehicles (AVs), drivers are tasked with remaining vigilant and ready to assume control should the system encounter a malfunction. However, little to no information is provided to the driver either about the AV's intended maneuvers or the AV's awareness of potential threats in the surrounding environment. To address this research gap, the present study proposes 2 human-machine interaction (HMI) concepts: Firstly, the shared intended pathway (SIP), which presents a forecast of the AV's intended maneuvers and, secondly, object recognition bounding boxes (ORBBs), which place transparent blue squares around other road users likely to contribute to a crash.
Direct reciprocity is a wide-spread mechanism for the evolution of cooperation. In repeated interactions, players can condition their behavior on previous outcomes. A well-known approach is given by reactive strategies, which respond to the coplayer's previous move.
