The structure and flexibility analysis of the Arabidopsis synaptotagmin 1 reveal the basis of its regulation at membrane contact sites

Non-vesicular lipid transfer at ER and plasma membrane (PM) contact sites (CS) is crucial for the maintenance of membrane lipid homeostasis. Extended synaptotagmins (E-Syts) play a central role in this process as they act as molecular tethers of ER and PM and as lipid transfer proteins between these organelles. E-Syts are proteins constitutively anchored to the ER through an N-terminal hydrophobic segment and bind the PM via a variable number of C-terminal C2 domains. Synaptotagmins (SYTs) are the plant orthologous of E-Syts and regulate the ER–PM communication in response to abiotic stress. Combining different structural and biochemical techniques, we demonstrate that the binding of SYT1 to lipids occurs through a Ca2+-dependent lipid-binding site and by a site for phosphorylated forms of phosphatidylinositol, thus integrating two different molecular signals in response to stress. In addition, we show that SYT1 displays three highly flexible hinge points that provide conformational freedom to facilitate lipid extraction, protein loading, and subsequent transfer between PM and ER.

Has Anyone Ever Been a Non-Intuitionist?

This paper considers the merits of an important argument of Prichard’s against Sidgwick’s claim that nobody has ever been an intuitionist. Prichard tries to turn the tables on that argument, arguing that nobody has ever been a non-intuitionist. This paper tries to adjudicate. One of the hinge points is the question in the philosophy of action where the distinction between an action and its consequences is supposed to lie. If enough of the consequences are sucked up into the action by understanding the latter as the action of causing those consequences, the structure of the debate changes. The discussion generates a much better understanding of ethical intuitionism and of the distinction between intuitionism and consequentialism.

Root Dilatation Is More Malignant Than Ascending Aortic Dilation

Background Data from the International Registry of Acute Aortic Dissection indicate that the guideline criterion of 5.5 cm for ascending aortic intervention misses many dissections occurring at smaller dimensions. Furthermore, studies of natural behavior have generally treated the aortic root and the ascending aorta as 1 unit despite embryological, anatomical, and functional differences. This study aims to disentangle the natural histories of the aforementioned aortic segments, allowing natural behavior to define specific intervention criteria for root and ascending segments of the aorta. Methods and Results Diameters of the aortic root and mid‐ascending segment were measured separately. Long‐term complications (dissection, rupture, and death) were analyzed retrospectively for 1162 patients with ascending thoracic aortic aneurysm. Cox regression analysis suggested that aortic root dilatation ( P =0.017) is more significant in predicting adverse events than mid‐ascending aortic dilatation ( P =0.087). Short stature posed as a serious risk factor. The dedicated risk curves for the aortic root and the mid‐ascending aorta revealed hinge points at 5.0 and 5.25 cm, respectively. Conclusions The natural histories of the aortic root and mid‐ascending aorta are uniquely different. Dilation of the aortic root imparts a significant higher risk of adverse events. A diameter shift for intervention to 5.0 cm for the aortic root and to 5.25 cm for the mid‐ascending aorta should be considered at expert centers.

Mechanistic Insights Revealed by YbtPQ in the Occluded State

Recently, several ATP-binding cassette (ABC) importers have been found to adopt the typical fold of type IV ABC exporters. Presumably, these importers would function under the transport scheme of "alternating access" like those exporters: cycling through conformations of inward-open, occluded, and outward-open. Understanding how the exporter-like importers move substrates in the opposite direction requires structural studies in all the major conformations. To shed light on that, here we report the structure of yersiniabactin importer YbtPQ from uropathogenic Escherichia coli in the occluded conformation trapped by ADP-vanadate (ADP.Vi) at 3.1 angstrom resolution determined by cryo electron microscopy. The structure shows unusual local rearrangements in multiple helices and loops in its transmembrane domains (TMDs). In addition, the dimerization of nucleotide-binding domains (NBDs) promoted by the vanadate trapping is highlighted by the "screwdriver" action happening at one of the two hinge points. These structural observations are rare and thus provide valuable information to understand the structural plasticity of the exporter-like ABC importers.

Selective Accommodation in Great Power Competition and U.S. Grand Strategy

This chapter examines a pair of scenarios built around hinge points in current U.S. grand strategy. The scenarios envision surprising departures from current alignment trends and prevailing precepts in U.S. foreign policy. One explores how China might undermine the deepening Indo-American partnership by accommodating India. The other explores how the United States might short-circuit the emerging Russia–China alliance by accommodating Russia. These scenarios show how the book's theoretical constructs may describe and explain future developments. They also illuminate potential changes in great power politics that today's orthodoxies in U.S. grand strategy make hard to imagine, let alone think about carefully. The chapter then concludes with commentary for policy practitioners seeking to make selective accommodation work.

Displacement of all three leaflets of tricuspid valve: a rare variant of Ebstein anomaly

Ebstein anomaly, a rare congenital heart disease, is defined as displacement of hinge points of septal or posterior tricuspid leaflets but not anterior leaflet. Here we report a 35 year old lady with an extremely rare pattern of EA with all three tricuspid leaflets displaced downward to the apex.

Myeloid cells, tissue homeostasis, and anatomical barriers as innate immune effectors in arterial hypertension

Although essential hypertension affects a large proportion of the human population and is one of the key drivers of cardiovascular mortality worldwide, we still do not have a complete understanding of its pathophysiology. More than 50 years ago, the immune system has been identified as an important part of the pathogenesis of arterial hypertension. An exceeding variety of recent publications deals with the interplay between the numerous different components of the immune system and mechanisms of arterial hypertension and has substantially contributed to our understanding of the role of immunity and inflammation in the pathogenesis of the disease. In this review, we focus on myeloid cells and anatomical barriers as particular aspects of innate immunity in arterial hypertension. Since it represents a first line of defense protecting against pathogens and maintaining tissue homeostasis, innate immunity provides many mechanistic hinge points in the area of hypertension.

Optimization of hinge point in luffing mechanism of aerial working vehicle based on PSO algorithm

Luffing mechanism is one of the important parts of aerial working vehicle, which plays a decisive role in the overall stability of boom system, the force of luffing cylinder and the force at each hinge point position. In this paper, the five hinge point luffing mechanism of aerial working vehicle is taken as the research object, and the force of its luffing cylinder under dangerous conditions is optimized. By studying the working principle of the boom system and the force analysis of the luffing mechanism, and then establishing the mechanical model, the objective function was optimized based on particle swarm algorithm and Matlab. The optimization results show that the maximum force on the luffing cylinder decreases by 18.9% with the optimized hinge points, which greatly improves the performance of the whole machine and provides a reference for the application of particle swarm optimization in construction machinery.

Design and analysis of a shape-transformable polyhedral mechanism with transformation between a truncated tetrahedron and a tetrahedron

The aim of this study is to present a novel shape-transformable polyhedral mechanism namely, the TrT–T mechanism, which can transform between a truncated tetrahedron and a common tetrahedron. The conceptual model of the TrT–T mechanism is proposed and described. For one-degree-of-freedom objective, a hexagonal planar linkage is chosen as a hexagonal interlinked unit to develop a solid model and fabricate a prototype. Mobility analysis is carried out based on screw theory. The inverse and forward kinematics are investigated, and the singularity is analyzed. The trajectories and velocities of the hinge points are described and explored. The prototype and simulation results demonstrate the feasibility of the TrT–T mechanism for shape transformation and validate the correctness of the mobility analysis. As a novel polyhedral linkage, the TrT–T mechanism can be potentially applied to modules with shape-transformation ability for constructing reconfigurable and modular robots.