Conserved GYXLI Motif of FlhA Is Involved in Dynamic Domain Motions of FlhA Required for Flagellar Protein Export.

Flagellar structural subunits are transported via the flagellar type III secretion system (fT3SS) and assemble at the distal end of the growing flagellar structure. The C-terminal cytoplasmic domain of FlhA (FlhA) serves as a docking platform for export substrates and flagellar chaperones and plays an important role in hierarchical protein targeting and export. FlhA consists of domains D1, D2, D3, and D4 and adopts open and closed conformations.

The FlhA linker mediates flagellar protein export switching during flagellar assembly.

The flagellar protein export apparatus switches substrate specificity from hook-type to filament-type upon hook assembly completion, thereby initiating filament assembly at the hook tip. The C-terminal cytoplasmic domain of FlhA (FlhA) serves as a docking platform for flagellar chaperones in complex with their cognate filament-type substrates. Interactions of the flexible linker of FlhA (FlhA) with its nearest FlhA subunit in the FlhA ring is required for the substrate specificity switching.

The flexible linker of the secreted FliK ruler is required for export switching of the flagellar protein export apparatus.

The hook length of the flagellum is controlled to about 55 nm in Salmonella. The flagellar type III protein export apparatus secretes FliK to determine hook length during hook assembly and changes its substrate specificity from the hook protein to the filament protein when the hook length has reached about 55 nm. Salmonella FliK consists of an N-terminal domain (FliK, residues 1-207), a C-terminal domain (FliK, residues 268-405) and a flexible linker (FliK, residues 208-267) connecting these two domains.

Direct observation of speed fluctuations of flagellar motor rotation at extremely low load close to zero.

The bacterial flagellar motor accommodates ten stator units around the rotor to produce large torque at high load. But when external load is low, some previous studies showed that a single stator unit can spin the rotor at the maximum speed, suggesting that the maximum speed does not depend on the number of active stator units, whereas others reported that the speed is also dependent on the stator number. To clarify these two controversial observations, much more precise measurements of motor rotation would be required at external load as close to zero as possible.

FliK-Driven Conformational Rearrangements of FlhA and FlhB Are Required for Export Switching of the Flagellar Protein Export Apparatus.

FlhA and FlhB are transmembrane proteins of the flagellar type III protein export apparatus, and their C-terminal cytoplasmic domains (FlhA and FlhB) coordinate flagellar protein export with assembly. FlhB undergoes autocleavage between Asn-269 and Pro-270 in a well-conserved NPTH loop located between FlhB and FlhB polypeptides and interacts with the C-terminal domain of the FliK ruler when the length of the hook has reached about 55 nm in As a result, the flagellar protein export apparatus switches its substrate specificity, thereby terminating hook assembly and initiating filament assembly. The mechanism of export switching remains unclear.

Ultralow-Noise Organic Transistors Based on Polymeric Gate Dielectrics with Self-Assembled Modifiers.

In this study, ultralow 1/ noise organic thin-film transistors (OTFTs) based on parylene gate dielectrics modified with triptycene (Trip) modifiers were fabricated. The fabricated OTFTs showed the lowest 1/ noise level among those of previously reported OTFTs. It is well known that 1/ noise causes degradation of signal integrity in analog and digital circuits.

Structural Insights into the Substrate Specificity Switch Mechanism of the Type III Protein Export Apparatus.

Bacteria use a type III protein export apparatus for construction of the flagellum, which consists of the basal body, the hook, and the filament. FlhA forms a homo-nonamer through its C-terminal cytoplasmic domains (FlhA) and ensures the strict order of flagellar assembly. FlhA goes through dynamic domain motions during protein export, but it remains unknown how it occurs.

Mutational analysis of the C-terminal cytoplasmic domain of FlhB, a transmembrane component of the flagellar type III protein export apparatus in Salmonella.

The flagellar protein export apparatus switches its substrate specificity when hook length has reached approximately 55 nm in Salmonella. The C-terminal cytoplasmic domain of FlhB (FlhB ) is involved in this switching process. FlhB consists of FlhB and FlhB polypeptides.

Novel Insights into Conformational Rearrangements of the Bacterial Flagellar Switch Complex.

The flagellar motor can spin in both counterclockwise (CCW) and clockwise (CW) directions. The flagellar motor consists of a rotor and multiple stator units, which act as a proton channel. The rotor is composed of the transmembrane MS ring made of FliF and the cytoplasmic C ring consisting of FliG, FliM, and FliN.

The use of combined T-weighted and FLAIR synthetic magnetic resonance images to improve white matter region contrast: a feasibility study.

Synthetic magnetic resonance imaging (MRI) allows the production of images with any contrast from a single scan after quantification. The combined T-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) image is expected to have an improved contrast between the normal-appearing white matter (WM) and WM lesion (WML). The purpose of this study was to determine whether optimal T contrast-weighted images (SyFLAIR) comprising the combined T2WI and FLAIR image generated using synthetic MRI could improve contrast in the WM region.

Insight into structural remodeling of the FlhA ring responsible for bacterial flagellar type III protein export.

The bacterial flagellum is a supramolecular motility machine. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. A carboxyl-terminal cytoplasmic domain of FlhA (FlhA) forms a nonameric ring structure in the flagellar type III protein export apparatus and coordinates flagellar protein export with assembly.

Evidence for the hook supercoiling mechanism of the bacterial flagellum.

The bacterial flagellar hook is a short, highly curved tubular structure connecting the basal body as a rotary motor and the filament as a helical propeller to function as a universal joint to transmit motor torque to the filament regardless of its orientation. This highly curved form is known to be part of a supercoil as observed in the polyhook structure. The subunit packing interactions in the hook structure solved in the straight form gave clear insights into the mechanisms of its bending flexibility and twisting rigidity.

Preference and strategy in proposer's prosocial giving in the ultimatum game.

The accumulation of findings that most responders in the ultimatum game reject unfair offers provides evidence that humans are driven by social preferences such as preferences for fairness and prosociality. On the other hand, if and how the proposer's behavior is affected by social preferences remains unelucidated. We addressed this question for the first time by manipulating the knowledge that the proposer had about the responder's belief concerning the intentionality of the proposer.

Novel insights into the mechanism of well-ordered assembly of bacterial flagellar proteins in Salmonella.

The FliI ATPase of the flagellar type III protein export apparatus forms the FliHFliI complex along with its regulator FliH. The FliHFliI complex is postulated to bring export substrates from the cytoplasm to the docking platform made of FlhA and FlhB although not essential for flagellar protein export. Here, to clarify the role of the FliHFliI complex in flagellar assembly, we analysed the effect of FliH and FliI deletion on flagellar protein export and assembly.

A triangular loop of domain D1 of FlgE is essential for hook assembly but not for the mechanical function.

The bacterial flagellar hook is a short, curved tubular structure made of FlgE. The hook connects the basal body as a rotary motor and the filament as a helical propeller and functions as a universal joint to smoothly transmit torque produced by the motor to the filament. Salmonella FlgE consists of D0, Dc, D1 and D2 domains.

The role of intrinsically disordered C-terminal region of FliK in substrate specificity switching of the bacterial flagellar type III export apparatus.

The bacterial flagellar export switching machinery consists of a ruler protein, FliK, and an export switch protein, FlhB and switches substrate specificity of the flagellar type III export apparatus upon completion of hook assembly. An interaction between the C-terminal domain of FliK (FliK ) and the C-terminal cytoplasmic domain of FlhB (FlhB ) is postulated to be responsible for this switch. FliK has a compactly folded domain termed FliK (residues 268-352) and an intrinsically disordered region composed of the last 53 residues, FliK (residues 353-405).

Straight and rigid flagellar hook made by insertion of the FlgG specific sequence into FlgE.

The bacterial flagellar hook connects the helical flagellar filament to the rotary motor at its base. Bending flexibility of the hook allows the helical filaments to form a bundle behind the cell body to produce thrust for bacterial motility. The hook protein FlgE shows considerable sequence and structural similarities to the distal rod protein FlgG; however, the hook is supercoiled and flexible as a universal joint whereas the rod is straight and rigid as a drive shaft.

Structural stability of flagellin subunit affects the rate of flagellin export in the absence of FliS chaperone.

FliS chaperone binds to flagellin FliC in the cytoplasm and transfers FliC to a sorting platform of the flagellar type III export apparatus through the interaction between FliS and FlhA for rapid and efficient protein export during flagellar filament assembly. FliS also suppresses the secretion of an anti-σ factor, FlgM. Loss of FliS results in a short filament phenotype although the expression levels of FliC are increased considerably due to an increase in the secretion level of FlgM.

FliH and FliI ensure efficient energy coupling of flagellar type III protein export in Salmonella.

For construction of the bacterial flagellum, flagellar proteins are exported via its specific export apparatus from the cytoplasm to the distal end of the growing flagellar structure. The flagellar export apparatus consists of a transmembrane (TM) export gate complex and a cytoplasmic ATPase complex consisting of FliH, FliI, and FliJ. FlhA is a TM export gate protein and plays important roles in energy coupling of protein translocation.

Effect of Duloxetine on Urethral Resting Pressure and on Sphincter Contractility in Response to Coughing and Magnetic Stimulation in Healthy Women.

Objectives: As a proof-of-mechanism (POM) study of drugs developed to treat stress urinary incontinence (SUI) has not been conducted, this urodynamic study in healthy women was performed to determine an appropriate method to confirm POM, and to evaluate the effect of duloxetine, a serotonin and noradrenaline reuptake inhibitor, on urethral resting pressure and on sphincter contractility in response to coughing and magnetic stimulation.

Methods: The urethral pressure profiles at rest, during coughing and during sacral root magnetic stimulation (SMS), and the motor threshold (MT) for urethral sphincter contraction in response to transcranial magnetic stimulation (TMS) were measured before and 6 h after the administration of 40 mg duloxetine in 10 healthy female subjects.

Results: Oral administration of duloxetine significantly increased the mean and maximal urethral closure pressures at rest over the proximal and middle third of the urethra.

[The effect of attainability on envy].

Envy is an unpleasant emotion caused by comparison with a person who possesses something we desire. We conducted two studies to test our prediction that less envy would be felt when the person could attain what others had. In Study 1, participants read scenarios in which their friend could achieve a goal which they could not, and rated their emotions toward the friend.

Reactive oxygen species from type-I photosensitized reactions contribute to the light-induced wilting of dark-grown pea (Pisum sativum) epicotyls.

Type-II, singlet oxygen-mediated photosensitized damage has already been shown to occur in epicotyls of dark-germinated pea (Pisum sativum L.) seedlings upon illumination, resulting in fast turgor loss and wilting. In this study we show evidence that the palette of reactive oxygen species (ROS) is more complex.