Modeling of the brain-lung axis using organoids in traumatic brain injury: an updated review.

Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin-Antitoxin System.

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

Spontaneous slow wave oscillations in extracellular field potential recordings reflect the alternating dominance of excitation and inhibition.

In the resting state, cortical neurons can fire action potentials spontaneously but synchronously (Up state), followed by a quiescent period (Down state) before the cycle repeats. Extracellular recordings in the infragranular layer of cortex with a micro-electrode display a negative deflection (depth-negative) during Up states and a positive deflection (depth-positive) during Down states. The resulting slow wave oscillation (SWO) has been studied extensively during sleep and under anaesthesia. However, recent research on the balanced nature of synaptic excitation and inhibition has highlighted our limited understanding of its genesis. Specifically, are excitation and inhibition balanced during SWOs? We analyse spontaneous local field potentials (LFPs) during SWOs recorded from anaesthetised rats via a multi-channel laminar micro-electrode and show that the Down state consists of two distinct synaptic states: a Dynamic Down state associated with depth-positive LFPs and a prominent dipole in the extracellular field, and a Static Down state with negligible ( ≈ 0 mV $ \approx 0{\mathrm{\;mV}}$ ) LFPs and a lack of dipoles extracellularly. We demonstrate that depth-negative and -positive LFPs are generated by a shift in the balance of synaptic excitation and inhibition from excitation dominance (depth-negative) to inhibition dominance (depth-positive) in the infragranular layer neurons. Thus, although excitation and inhibition co-tune overall, differences in their timing lead to an alternation of dominance, manifesting as SWOs. We further show that Up state initiation is significantly faster if the preceding Down state is dynamic rather than static. Our findings provide a coherent picture of the dependence of SWOs on synaptic activity. KEY POINTS: Cortical neurons can exhibit repeated cycles of spontaneous activity interleaved with periods of relative silence, a phenomenon known as 'slow wave oscillation' (SWO). During SWOs, recordings of local field potentials (LFPs) in the neocortex show depth-negative deflection during the active period (Up state) and depth-positive deflection during the silent period (Down state). Here we further classified the Down state into a dynamic phase and a static phase based on a novel method of classification and revealed non-random, stereotypical sequences of the three states occurring with significantly different transitional kinetics. Our results suggest that the positive and negative deflections in the LFP reflect the shift of the instantaneous balance between excitatory and inhibitory synaptic activity of the local cortical neurons. The differences in transitional kinetics may imply distinct synaptic mechanisms for Up state initiation. The study may provide a new approach for investigating spontaneous brain rhythms.

Structural Insights into the Penicillin-Binding Protein 4 (DacB) from Mycobacterium tuberculosis.

Mycobacterium tuberculosis, a major cause of mortality from a single infectious agent, possesses a remarkable mycobacterial cell envelope. Penicillin-Binding Proteins (PBPs) are a family of bacterial enzymes involved in the biosynthesis of peptidoglycan. PBP4 (DacB) from M. tuberculosis (MtbPBP4) has been known to function as a carboxypeptidase, and the role and significance of carboxypeptidases as targets for anti-tuberculosis drugs or antibiotics have been extensively investigated over the past decade. However, their precise involvement remains incompletely understood. In this study, we employed predictive modeling and analyzed the three-dimensional structure of MtbPBP4. Interestingly, MtbPBP4 displayed a distinct domain structure compared to its homologs. Docking studies with meropenem verified the presence of active site residues conserved in PBPs. These findings establish a structural foundation for comprehending the molecular function of MtbPBP4 and offer a platform for the exploration of novel antibiotics.

A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.

BACKGROUND: Subjective cognitive decline (SCD) refers to the self-reported persistent cognitive decline despite normal objective testing, increasing the risk of dementia compared to cognitively normal individuals. OBJECTIVE: This study aims to investigate the attributes of SCD patients who demonstrated memory function improvement. METHODS: In this prospective study of SCD, a total of 120 subjects were enrolled as part of a multicenter cohort study aimed at identifying predictors for the clinical progression to mild cognitive impairment or dementia (CoSCo study). All subjects underwent 18F-florbetaben PET and brain MRI scans at baseline and annual neuropsychological tests. At the 24-month follow-up, we classified SCD patients based on changes in memory function, the z-score of the Seoul verbal learning test delayed recall. RESULTS: Of the 120 enrolled patients, 107 successfully completed the 24-month follow-up assessment. Among these, 80 patients (74.8%) with SCD exhibited memory function improvements. SCD patients with improved memory function had a lower prevalence of coronary artery disease at baseline and performed better in the trail-making test part B compared to those without improvement. Anatomical and biomarker analysis showed a lower frequency of amyloid PET positivity and larger volumes in the left and right superior parietal lobes in subjects with improved memory function. CONCLUSIONS: Our prospective study indicates that SCD patients experiencing memory improvement over a 24-month period had a lower amyloid burden, fewer cardiovascular risk factors, and superior executive cognitive function. Identifying these key factors associated with cognitive improvement may assist clinicians in predicting future memory function improvements in SCD patients.

A Facile Method to Fabricate an Enclosed Paper-Based Analytical Device via Double-Sided Patterning for Ionic Contaminant Detection.

Microfluidic paper-based analytical devices (µPADs) have been developed for use in a variety of diagnosis and analysis fields. However, conventional µPADs with an open-channel system have limitations for application as analytical platforms mainly because of the evaporation and contamination of the sample solution. This study demonstrates the design and fabrication of an enclosed three-dimensional(3D)-µPAD and its application as a primary early analysis platform for ionic contaminants. To generate the hydrophobic PDMS barrier, double-sided patterning is carried out using a PDMS blade-coated stamp mold that is fabricated using 3D printing. The selective PDMS patterning can be achieved with controlled PDMS permeation of the cellulose substrate using 3D-designed stamp molds. We find the optimal conditions enabling the formation of enclosed channels, including round shape pattern and inter-pattern distance of 10 mm of stamp design, contact time of 0.5 min, and spacer height of 300 µm of double-sided patterning procedure. As a proof of concept, this enclosed 3D-µPAD is used for the simultaneous colorimetric detection of heavy metal ions in a concentration range of 0.1-2000 ppm, including nickel (Ni2+), copper (Cu2+), mercury (Hg2+), and radioactive isotope cesium-137 ions (Cs+). We confirm that qualitative analysis and image-based quantitative analysis with high reliability are possible through rapid color changes within 3 min. The limits of detection (LOD) for 0.55 ppm of Ni2+, 5.05 ppm of Cu2+, 0.188 ppm of Hg2+, and 0.016 ppm of Cs+ are observed, respectively. In addition, we confirm that the analysis is highly reliable in a wide range of ion concentrations with CV values below 3% for Ni2+ (0.56%), Cu2+ (0.45%), Hg2+ (1.35%), and Cs+ (2.18%). This method could be a promising technique to develop a 3D-µPAD with various applications as a primary early analysis device in the environmental and biological industries.

Focused Overview of Mycobacterium tuberculosis VapBC Toxin-Antitoxin Systems Regarding Their Structural and Functional Aspects: Including Insights on Biomimetic Peptides.

Tuberculosis, caused by Mycobacterium tuberculosis, is a lethal infectious disease of significant public health concern. The rise of multidrug-resistant and drug-tolerant strains has necessitated novel approaches to combat the disease. Toxin-antitoxin (TA) systems, key players in bacterial adaptive responses, are prevalent in prokaryotic genomes and have been linked to tuberculosis. The genome of M. tuberculosis strains harbors an unusually high number of TA systems, prompting questions about their biological roles. The VapBC family, a representative type II TA system, is characterized by the VapC toxin, featuring a PilT N-terminal domain with nuclease activity. Its counterpart, VapB, functions as an antitoxin, inhibiting VapC's activity. Additionally, we explore peptide mimics designed to replicate protein helical structures in this review. Investigating these synthetic peptides offers fresh insights into molecular interactions, potentially leading to therapeutic applications. These synthetic peptides show promise as versatile tools for modulating cellular processes and protein-protein interactions. We examine the rational design strategies employed to mimic helical motifs, their biophysical properties, and potential applications in drug development and bioengineering. This review aims to provide an in-depth understanding of TA systems by introducing known complex structures, with a focus on both structural aspects and functional and molecular details associated with each system.

Three Distinct Polar Phases, Isotropic, Nematic, and Smectic-A Phases, Formed from a Fluoro-Substituted Dimeric Molecule with Large Dipole Moment.

A dimeric molecule, di-5(3FM-C4T), with fluoro-substituted mesogenic cores composed of three-aromatic rings and linked by a pentamethylene spacer is prepared. Di-5(3FM-C4T) forms the ferroelectric nematic (NF), ferroelectric smectic-A (SmAPF), and polar isotropic (IsoP) phases. The NF phase is composed of molecules in U-shaped conformation that behave like polar rod-like molecules. The reversal spontaneous polarization (Ps) is approximately 8 µC cm-2, which is extremely large and reflects the huge dipole moment (11.2 D) of the one-side mesogenic core. On the other hand, the SmAPF phase is formed by bent-shaped molecules. The NF-SmAPF phase transition thus follows the conformational change of molecules. The reversal Ps of the SmAPF phase is around 4 µC cm-2, which is half of that in the NF phase, and this is an expected value from the bent shape of the molecules. It is interesting that the highest temperature IsoP phase still exhibits the polar structure and possibly retains some polar aggregation of molecules in small domains. The three polar phases exhibit the dielectric mode due to the collective polarization fluctuation at around 100 Hz, giving the high dielectric constant over 8000.

Mycobacterium tuberculosis Rv0229c Shows Ribonuclease Activity and Reveals Its Corresponding Role as Toxin VapC51.

The VapBC system, which belongs to the type II toxin-antitoxin (TA) system, is the most abundant and widely studied system in Mycobacterium tuberculosis. The VapB antitoxin suppresses the activity of the VapC toxin through a stable protein-protein complex. However, under environmental stress, the balance between toxin and antitoxin is disrupted, leading to the release of free toxin and bacteriostatic state. This study introduces the Rv0229c, a putative VapC51 toxin, and aims to provide a better understanding of its discovered function. The structure of the Rv0229c shows a typical PIN-domain protein, exhibiting an ß1-α1-α2-ß2-α3-α4-ß3-α5-α6-ß4-α7-ß5 topology. The structure-based sequence alignment showed four electronegative residues in the active site of Rv0229c, which is composed of Asp8, Glu42, Asp95, and Asp113. By comparing the active site with existing VapC proteins, we have demonstrated the justification for naming it VapC51 at the molecular level. In an in vitro ribonuclease activity assay, Rv0229c showed ribonuclease activity dependent on the concentration of metal ions such as Mg2+ and Mn2+. In addition, magnesium was found to have a greater effect on VapC51 activity than manganese. Through these structural and experimental studies, we provide evidence for the functional role of Rv0229c as a VapC51 toxin. Overall, this study aims to enhance our understanding of the VapBC system in M. tuberculosis.

GDNF family receptor alpha-like antagonist antibody alleviates chemotherapy-induced cachexia in melanoma-bearing mice.

BACKGROUND: Patients with cancer undergoing chemotherapy experience cachexia with anorexia, body weight loss, and the depletion of skeletal muscles and adipose tissues. Effective treatment strategies for chemotherapy-induced cachexia are scarce. The growth differentiation factor 15 (GDF15)/GDNF family receptor alpha-like (GFRAL)/rearranged during transfection (RET) axis is a critical signalling pathway in chemotherapy-induced cachexia. In this study, we developed a fully human GFRAL antagonist antibody and investigated whether it inhibits the GDF15/GFRAL/RET axis, thereby alleviating chemotherapy-induced cachexia in tumour-bearing mice. METHODS: Anti-GFRAL antibodies were selected via biopanning, using a human combinatorial antibody phage library. The potent GFRAL antagonist antibody A11 was selected via a reporter cell assay and its inhibitory activity of GDF15-induced signalling was evaluated using western blotting. To investigate the in vivo function of A11, a tumour-bearing mouse model was established by inoculating 8-week-old male C57BL/6 mice with B16F10 cells (n = 10-16 mice per group). A11 was administered subcutaneously (10 mg/kg) 1 day before intraperitoneal treatment with cisplatin (10 mg/kg). Animals were assessed for changes in food intake, body weight, and tumour volume. Plasma and key metabolic tissues such as skeletal muscles and adipose tissues were collected for protein and mRNA expression analysis. RESULTS: A11 reduced serum response element-luciferase reporter activity up to 74% (P < 0.005) in a dose-dependent manner and blocked RET phosphorylation up to 87% (P = 0.0593), AKT phosphorylation up to 28% (P = 0.0593) and extracellular signal regulatory kinase phosphorylation up to 75% (P = 0.0636). A11 inhibited the action of cisplatin-induced GDF15 on the brainstem and decreased GFRAL-positive neuron population expressing c-Fos in the area postrema and nucleus of the solitary tract by 62% in vivo (P < 0.05). In a melanoma mouse model treated with cisplatin, A11 recovered anorexia by 21% (P < 0.05) and tumour-free body weight loss by 13% (P < 0.05). A11 significantly improved the cisplatin-induced loss of skeletal muscles (quadriceps: 21%, gastrocnemius: 9%, soleus: 13%, P < 0.05) and adipose tissues (epididymal white adipose tissue: 37%, inguinal white adipose tissue: 51%, P < 0.05). CONCLUSIONS: Our study suggests that GFRAL antagonist antibody may alleviate chemotherapy-induced cachexia, providing a novel therapeutic approach for patients with cancer experiencing chemotherapy-induced cachexia.

Domain swapping of the C-terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis.

Polyketide metabolism-associated proteins in Mycobacterium tuberculosis play an essential role in the survival of the bacterium, which makes them potential drug targets for the treatment of tuberculosis (TB). The novel ribonuclease protein Rv1546 is predicted to be a member of the steroidogenic acute regulatory protein-related lipid-transfer (START) domain superfamily, which comprises bacterial polyketide aromatase/cyclases (ARO/CYCs). Here, we determined the crystal structure of Rv1546 in a V-shaped dimer. The Rv1546 monomer consists of four α-helices and seven antiparallel ß-strands. Interestingly, in the dimeric state, Rv1546 forms a helix-grip fold, which is present in START domain proteins, via three-dimensional domain swapping. Structural analysis revealed that the conformational change of the C-terminal α-helix of Rv1546 might contribute to the unique dimer structure. Site-directed mutagenesis followed by in vitro ribonuclease activity assays was performed to identify catalytic sites of the protein. This experiment suggested that surface residues R63, K84, K88, and R113 are important in the ribonuclease function of Rv1546. In summary, this study presents the structural and functional characterization of Rv1546 and supplies new perspectives for exploiting Rv1546 as a novel drug target for TB treatment.

A high sensitivity acetone gas sensor based on polyaniline-hydroxypropyl methylcellulose core-shell-shaped nanoparticles.

Core-shell-shaped nanoparticles (CSS-NPs) with polyaniline emeraldine salts (PANi) in the core and hydroxypropyl methylcellulose (HPMC) and heptadecafluorooctanesulfonic acid (C8F) shells, i.e., C8F-doped PANi@HPMC CSS-NPs, were synthesized as a gaseous acetone sensing material with high sensitivity and humidity stability. The HPMC was chemically combined on the positively charged PANi NPs' outer surface, allowing it to efficiently detect acetone gas at concentrations as low as 50 ppb at 25 °C. To impart humidity stability, C8F was employed as a hydrophobic dopant, and a valid signal could be reliably detected even in the range of 0-80% relative humidity. The sensing material's structural analysis was conducted using scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and infrared spectroscopy, and in particular, the reaction mechanism with acetone gas was detected through a spectroscopic method. Thus, these findings illustrate the potential as a novel sensing material to detect acetone gas at a trace level of less than 1 ppm in human respiratory gas.

Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer effects through miRNA delivery.

T cell-derived small extracellular vesicles (sEVs) exhibit anti-cancer effects. However, their anti-cancer potential should be reinforced to enhance clinical applicability. Herein, we generated interleukin-2-tethered sEVs (IL2-sEVs) from engineered Jurkat T cells expressing IL2 at the plasma membrane via a flexible linker to induce an autocrine effect. IL2-sEVs increased the anti-cancer ability of CD8+ T cells without affecting regulatory T (Treg ) cells and down-regulated cellular and exosomal PD-L1 expression in melanoma cells, causing their increased sensitivity to CD8+ T cell-mediated cytotoxicity. Its effect on CD8+ T and melanoma cells was mediated by several IL2-sEV-resident microRNAs (miRNAs), whose expressions were upregulated by the autocrine effects of IL2. Among the miRNAs, miR-181a-3p and miR-223-3p notably reduced the PD-L1 protein levels in melanoma cells. Interestingly, miR-181a-3p increased the activity of CD8+ T cells while suppressing Treg cell activity. IL2-sEVs inhibited tumour progression in melanoma-bearing immunocompetent mice, but not in immunodeficient mice. The combination of IL2-sEVs and existing anti-cancer drugs significantly improved anti-cancer efficacy by decreasing PD-L1 expression in vivo. Thus, IL2-sEVs are potential cancer immunotherapeutic agents that regulate both immune and cancer cells by reprogramming miRNA levels.

Spontaneous Polarization Characteristics in Polar Smectic Phases of Fluoro-Substituted Bent-Shaped Dimeric Molecules.

Three kinds of bent-shaped dimeric molecules are synthesized by fluorine substitution of C16 molecules, and influences of the substitution on the polar smectic phases are examined. The fluorine-substituted C16 molecules form the SmAPF and SmCAPA phases. The transition temperatures decrease by 20-30 °C without significantly changing the temperature span of the smectic phase, and the switching rates to the ferroelectric state become 5-10 µs, which are fairly shorter than 250 µs of C16. These behaviors are considered to be caused by the decrease in the intermolecular force and the decrease in the viscosity. The anchoring behavior also appears to be different. On the indium tin oxide (ITO)-coated cell, the fluorine-substituted molecules are homogeneously aligned with the bent (polar) axes perpendicular to the surface, while the bent axes of ordinary bent-shaped molecules lie parallel to the surface. This may be attributable to the repulsion between the fluorine and ITO electrodes. Further, the fluorine substitution can increase the dipole moment of the molecule. The largest dipole moment obtained is 7.94 D, and this leads to a huge reversal polarization of 2.42 µC cm-2, which is much higher compared to those reported in the bent-shaped molecules.

The Fabrication of Cesium Lead Bromide-Coated Cellulose Nanocomposites and Their Effect on the Detection of Nitrogen Gas.

In this work, we fabricate cesium lead bromide nanofibers (CsPbBr3 NFs) via the attachment of cesium lead bromide nanocrystals (CsPbBr3 NCs) on the surface of electrospun cellulose nanofibers (CNFs) and employ them in a sensor to effectively detect gaseous nitrogen. The CsPbBr3 NFs are produced initially by producing CsPbBr3 NCs through hot injection and dispersing on hexane, followed by dipping CNFs and ultrasonicate for 1 h. Morphological characterization through visual, SEM and TEM image, and crystalline structure analysis by XRD and FT-IR analysis of CsPbBr3 NFs and NCs show similar spectra except for PL due to unavoidable damage during the ultrasonication. Gaseous nitrogen is subsequently detected using the photoluminescence (PL) property of CsPbBr3 NFs, in which the PL intensity dramatically decreases under various flow rate. Therefore, we believe that the proposed CsPbBr3 NFs show significant promise for use in detection sensors in various industrial field and decrease the potential of fatal damage to workers due to suffocation.

Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles.

Extracellular vesicles (EVs) mediate cell-cell crosstalk by carrying bioactive molecules derived from cells. Recently, immune cell-derived EVs have been reported to regulate key biological functions such as tumor progression. CD4+ T cells orchestrate overall immunity; however, the biological role of their EVs is unclear. This study reveals that EVs derived from CD4+ T cells increase the antitumor response of CD8+ T cells by enhancing their proliferation and activity without affecting regulatory T cells (Tregs). Moreover, EVs derived from interleukin-2 (IL2)-stimulated CD4+ T cells induce a more enhanced antitumor response of CD8+ T cells compared with that of IL2-unstimulated CD4+ T cell-derived EVs. Mechanistically, miR-25-3p, miR-155-5p, miR-215-5p, and miR-375 within CD4+ T cell-derived EVs are responsible for the induction of CD8+ T cell-mediated antitumor responses. In a melanoma mouse model, the EVs potently suppress tumor growth through CD8+ T cell activation. This study demonstrates that the EVs, in addition to IL2, are important mediators between CD4+ and CD8+ T cells. Furthermore, unlike IL2, clinically used as an antitumor agent, CD4+ T cell-derived EVs stimulate CD8+ T cells without activating Tregs. Therefore, CD4+ T cell-derived EVs may provide a novel direction for cancer immunotherapy by inducing a CD8+ T cell-mediated antitumor response.

The Haemophilus influenzae HipBA toxin-antitoxin system adopts an unusual three-com-ponent regulatory mechanism.

Type II toxin-antitoxin (TA) systems encode two proteins: a toxin that inhibits cell growth and an antitoxin that neutralizes the toxin by direct inter-molecular protein-protein inter-actions. The bacterial HipBA TA system is implicated in persister formation. The Haemophilus influenzae HipBA TA system consists of a HipB antitoxin and a HipA toxin, the latter of which is split into two fragments, and here we investigate this novel three-com-ponent regulatory HipBA system. Structural and functional analysis revealed that HipAN corresponds to the N-ter-minal part of HipA from other bacteria and toxic HipAC is inactivated by HipAN, not HipB. This study will be helpful in understanding the detailed regulatory mechanism of the HipBAN+C system, as well as why it is constructed as a three-com-ponent system.

Electric Switching Behaviors and Dielectric Relaxation Properties in Ferroelectric, Antiferroelectric, and Paraelectric Smectic Phases of Bent-Shaped Dimeric Molecules.

This study reports the electric switching behaviors and dielectric properties of the ferroelectric smectic-A (SmAPF), anti-ferroelectric smectic-A (SmAPA), anti-ferroelectric SmCAPA, and smectic-A (SmA) phases formed by mixing the bent-shaped dimeric molecules, α,ω-bis(4-alkoxyanilinebenzylidene-4'-carbonyloxy)pentanes. These four phases each show characteristic features. The SmAPF shows a low threshold electric field for ferroelectric switching and a large dielectric strength due to the collective fluctuation mode of dipoles at around 500 Hz. Both the threshold electric field and dielectric strength are strongly dependent on the cell thickness. The threshold field decreases to 0.1 V µm-1, and the dielectric strength increases up to a huge value of 10,000 as the cell thickness increases up to 80 µm. The SmAPA also shows a similar collective mode at around 2 kHz with a relatively small dielectric strength (around 200), which may be induced by the anti-phase rotation of dipoles in adjacent layers. In these collective modes, the dielectric strength is found to be inversely proportional to the switching threshold field. On the other hand, another anti-ferroelectric SmCAPA as well as the paraelectric SmA show only the non-collective mode (i.e., rotational relaxation of individual molecules around their short axes) at a high frequency of around 100 kHz.

Acetone Gas Sensor Based on SWCNT/Polypyrrole/Phenyllactic Acid Nanocomposite with High Sensitivity and Humidity Stability.

We synthesized core-shell-shaped nanocomposites composed of a single-walled carbon nanotube (SWCNT) and heptadecafluorooctanesulfonic acid-doped polypyrrole (C8F-doped-PPy)/phenyllatic acid (PLA), i.e., C8F-doped-PPy/PLA@SWCNT, for detecting acetone gas with high sensitivity and humidity stability. The obtained nanocomposites have the structural features of a sensing material as a C8F-doped-PPy layer surrounding a single-stranded SWCNT, and a PLA layer on the outer surface of the PPy as a specific sensing layer for acetone. PLA was chemically combined with the positively charged PPy backbone and provided the ability to reliably detect acetone gas at concentrations as low as 50 ppb even at 25 °C, which is required for medical diagnoses via human breath analysis. When C8F was contained in the pyrrole monomer in a ratio of 0.1 mol, it was able to stably detect an effective signal in a relative humidity (RH) of 0-80% range.

Role of PemI in the Staphylococcus aureus PemIK toxin-antitoxin complex: PemI controls PemK by acting as a PemK loop mimic.

Staphylococcus aureus is a notorious and globally distributed pathogenic bacterium. New strategies to develop novel antibiotics based on intrinsic bacterial toxin-antitoxin (TA) systems have been recently reported. Because TA systems are present only in bacteria and not in humans, these distinctive systems are attractive targets for developing antibiotics with new modes of action. S. aureus PemIK is a type II TA system, comprising the toxin protein PemK and the labile antitoxin protein PemI. Here, we determined the crystal structures of both PemK and the PemIK complex, in which PemK is neutralized by PemI. Our biochemical approaches, including fluorescence quenching and polarization assays, identified Glu20, Arg25, Thr48, Thr49, and Arg84 of PemK as being important for RNase function. Our study indicates that the active site and RNA-binding residues of PemK are covered by PemI, leading to unique conformational changes in PemK accompanied by repositioning of the loop between ß1 and ß2. These changes can interfere with RNA binding by PemK. Overall, PemK adopts particular open and closed forms for precise neutralization by PemI. This structural and functional information on PemIK will contribute to the discovery and development of novel antibiotics in the form of peptides or small molecules inhibiting direct binding between PemI and PemK.