Activation of TMEM16E scramblase induces ligand independent growth factor receptor signaling and macropinocytosis for membrane repair.

The calcium-dependent phospholipid scramblase TMEM16E mediates ion transport and lipid translocation across the plasma membrane. TMEM16E also contributes to protection of membrane structure by facilitating cellular repair signaling. Our research reveals that TMEM16E activation promotes macropinocytosis, essential for maintaining plasma membrane integrity.

Development of Test Cases for Automated Vehicle Driving Safety Assessment Using Driving Trajectories.

For consumers to have confidence in the safety of automated vehicles (AVs), AVs must be assessed using systematically developed scenarios to verify driving safety and reliability. In particular, verification using scenarios has been widely performed for the assessment and certification of AVs. This study aims to develop test cases based on driving trajectories to assess the driving safety of AVs.

The plasma membrane inner leaflet PI(4,5)P is essential for the activation of proton-activated chloride channels.

Proton-activated chloride (PAC) channels, ubiquitously expressed in tissues, regulate intracellular Cl levels and cell death following acidosis. However, molecular mechanisms and signaling pathways involved in PAC channel modulation are largely unknown. Herein, we determine that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] of the plasma membrane inner leaflet is essential for the proton activation of PAC channels.

Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.

Background: CT-P43 is a candidate ustekinumab biosimilar in clinical development.

Objectives: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis.

Methods: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I.

Development of a Framework for Generating Driving Safety Assessment Scenarios for Automated Vehicles.

Despite the technological advances in automated driving systems, traffic accidents involving automated vehicles (AVs) continue to occur, raising concerns over the safety and reliability of automated driving. For the smooth commercialization of AVs, it is necessary to systematically assess the driving safety of AVs under the various situations that they potentially face. In this context, these various situations are mostly implemented by using systematically developed scenarios.

Development of freeway-based test scenarios for applying new car assessment program to automated vehicles.

As automated driving technology continues to develop, studies are being conducted to develop various scenarios for assessing the functional safety, failure safety, and mobility of automated vehicles (AVs). As the commercialization of AVs progresses, it is necessary to develop a set of test scenarios for new car assessment programs (NCAPs), so as to provide information on the safety and reliability of AVs to consumers. To provide valuable information regarding newly emerged AVs to consumers who are willing to purchase them, it is necessary to derive specific and well-defined test scenarios based on the safety-in-use.

Differential Regulation of Ca-Activated Cl Channel TMEM16A Splice Variants by Membrane PI(4,5)P.

TMEM16A is a Ca-activated Cl channel that controls broad cellular processes ranging from mucus secretion to signal transduction and neuronal excitability. Recent studies have reported that membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) is an important cofactor that allosterically regulates TMEM16A channel activity. However, the detailed regulatory actions of PIP in splice variants of TMEM16A remain unclear.

Allosteric modulation of alternatively spliced Ca-activated Cl channels TMEM16A by PI(4,5)P and CaMKII.

Transmembrane 16A (TMEM16A, anoctamin1), 1 of 10 TMEM16 family proteins, is a Cl channel activated by intracellular Ca and membrane voltage. This channel is also regulated by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P]. We find that two splice variants of TMEM16A show different sensitivity to endogenous PI(4,5)P degradation, where TMEM16A(ac) displays higher channel activity and more current inhibition by PI(4,5)P depletion than TMEM16A(a).

Proteogenomic analysis of NCC-S1M, a gastric cancer stem cell-like cell line that responds to anti-PD-1.

To elucidate signaling pathways that regulate gastric cancer stem cell (CSC) phenotypes and immune checkpoint, we performed a proteogenomic analysis of NCC-S1M, which is a gastric cancer cell line with CSC-like characteristics and is the only syngeneic gastric tumor cell line transplant model created in the scientific community. We found that the NCC-S1M allograft was responsive to anti-PD-1 treatment, and overexpressed Cd274 encoding PD-L1. PD-L1 was transcriptionally activated by loss of the TGF-β signaling.