Identification of specific microbiota members that induce beige fat biogenesis in response to dietary cues.

Activation of brown and beige fat biogenesis promotes metabolic health in rodents and humans, but typically requires cold exposure or pharmacological activation of β-adrenergic receptors, which may pose cardiovascular risks. Dietary intervention represents a clinically viable alternative strategy to induce beige cells and thus enhance metabolic health, though the underlying mechanisms remain poorly understood. In this study, we identified specific microbiota members in both mice and humans that promote browning of white adipose tissue (WAT) and ameliorate metabolic disorders in the context of a low-protein diet (LPD).

Site-Specific Clustering of Bioactive Signaling Molecules Predicted In Situ by Space and Time Coherent Mapping for Imaging Mass Spectrometry.

Anatomical representation of site-specific clustering of biomolecules is a powerful way of predicting a potential interaction among signaling cascades and orchestrating molecular functions in cells and organs. The greater the number of molecules visualized simultaneously, the deeper we can understand each molecule's role in cellular metabolism and function. In the present study, we investigated site-specific localization of small biomolecules in the slug using Space and Time Coherent Mapping (STCM), a key technology in matrix-assisted laser desorption ionization time-of-flight imaging mass spectrometry.

Single molecule tracking based drug screening.

The single-molecule tracking of transmembrane receptors in living cells has provided significant insights into signaling mechanisms, such as mobility and clustering upon their activation/inactivation, making it a potential screening method for drug discovery. Here we show that single-molecule tracking-based screening can be used to explore compounds both detectable and undetectable by conventional methods for disease-related receptors. Using an automated system for a fast large-scale single-molecule analysis, we screen for epidermal growth factor receptor (EGFR) from 1134 of FDA approved drugs.

Commensal consortia decolonize Enterobacteriaceae via ecological control.

Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae.

Application of single-molecule analysis to singularity phenomenon of cells.

Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics.

Spontaneous signal generation by an excitable system for cell migration.

Eukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the migrating cell be generated spontaneously from the intrinsic activities of intracellular signaling networks.

Left-right Myosin-Is, Myosin1C, and Myosin1D exhibit distinct single molecule behaviors on the plasma membrane of Drosophila macrophages.

Left-right (LR) asymmetry is crucial for animal development, particularly in Drosophila where LR-asymmetric morphogenesis of organs hinges on cellular-level chirality, termed cell chirality. In this species, two class I myosins, Myosin1D (Myo1D), and Myosin1C (Myo1C), respectively determine dextral (wild type) and sinistral (mirror image) cell chirality. Previous studies demonstrated Myo1D's ability to propel F-actin in leftward circles during in vitro gliding assays, suggesting its mechanochemical role in defining dextral chirality.

[Validation of the Qualitative Study Findings using Quantitative Analyses on the Current Status of Pharmacists in Home Health Care in Medium-Sized Areas].

Although the issue of home medical care and pharmacists remains widespread, much of the discussion has concentrated on its state in urban areas. We believe that it is necessary to consider the state of home health care in medium-sized regions, that is separate from its urban form, with a population of approximately 100000. Thus, we conducted a qualitative study in Hikone City, Shiga Prefecture, to identify factors that impede pharmacists involved in home medical care.

Cholesterol suppresses spontaneous activation of EGFR-mediated signal transduction.

Epidermal growth factor receptor (EGFR)-mediated signal transduction controls cell growth and proliferation. The signaling pathway is regulated so that it is activated only by external EGF stimuli, but the mechanisms that prevent EGF-independent spontaneous activation of EGFR-mediated signaling are unknown. Here we report cholesterol depletion activates EGFR-mediated signaling without EGF.

A dynamic partitioning mechanism polarizes membrane protein distribution.

The plasma membrane is widely regarded as the hub of the numerous signal transduction activities. Yet, the fundamental biophysical mechanisms that spatiotemporally compartmentalize different classes of membrane proteins remain unclear. Using multimodal live-cell imaging, here we first show that several lipid-anchored membrane proteins are consistently depleted from the membrane regions where the Ras/PI3K/Akt/F-actin network is activated.

Rationally-defined microbial consortia suppress multidrug-resistant proinflammatory Enterobacteriaceae via ecological control.

Persistent colonization and outgrowth of pathogenic organisms in the intestine may occur due to long-term antibiotic usage or inflammatory conditions, which perpetuate dysregulated immunity and tissue damage. Gram-negative gut pathobionts are particularly recalcitrant to conventional antibiotic treatment, though an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy. In this study, we rationally isolated and down-selected commensal bacterial consortia from healthy human stool samples capable of strongly and specifically suppressing intestinal .

The specific core fucose-binding lectin Pholiota squarrosa lectin (PhoSL) inhibits hepatitis B virus infection in vitro.

Glycosylation of proteins and lipids in viruses and their host cells is important for viral infection and is a target for antiviral therapy. Hepatitis B virus (HBV) is a major pathogen that causes acute and chronic hepatitis; it cannot be cured because of the persistence of its covalently closed circular DNA (cccDNA) in hepatocytes. Here we found that Pholiota squarrosa lectin (PhoSL), a lectin that specifically binds core fucose, bound to HBV particles and inhibited HBV infection of a modified human HepG2 cell line, HepG2-hNTCP-C4, that expresses an HBV receptor, sodium taurocholate cotransporting polypeptide.

A dynamic partitioning mechanism polarizes membrane protein distribution.

The plasma membrane is widely regarded as the hub of the signal transduction network activities that drives numerous physiological responses, including cell polarity and migration. Yet, the symmetry breaking process in the membrane, that leads to dynamic compartmentalization of different proteins, remains poorly understood. Using multimodal live-cell imaging, here we first show that multiple endogenous and synthetic lipid-anchored proteins, despite maintaining stable tight association with the inner leaflet of the plasma membrane, were unexpectedly depleted from the membrane domains where the signaling network was spontaneously activated such as in the new protrusions as well as within the propagating ventral waves.

Field model for multistate lateral diffusion of various transmembrane proteins observed in living Dictyostelium cells.

The lateral diffusion of transmembrane proteins on plasma membranes is a fundamental process for various cellular functions. Diffusion properties specific for individual protein species have been extensively studied, but the common features among protein species are poorly understood. Here, we systematically studied the lateral diffusion of various transmembrane proteins in the lower eukaryote Dictyostelium discoideum cells using a hidden Markov model for single-molecule trajectories obtained experimentally.

[Survey in Hyogo Prefecture on the Current Status of Pharmacists in Home Health Care and Exploration of Factors Causing Psychological Burden].

There is a need for pharmacists to be actively involved in home healthcare through a wide range of collaboration in healthcare and welfare. However, insufficient evidence is available to search for factors that prevent pharmacists from being proactive in home healthcare. In this study, we conducted an extensive questionnaire survey among pharmacists engaged in home pharmacy work who belong to the Hyogo Pharmaceutical Society regarding the current status of pharmacists' work in home medical care and their psychological burden; we also explored the factors that may hinder the future development of home medical care.

Effect of prior knowledge and peer evaluation ratings on final exam performance in a team-based learning chemistry course.

Introduction: Various reports have been published regarding adoption of team-based learning (TBL) in pharmacy education. However, there is insufficient published evidence on the effect of student characteristics on student learning outcomes in a TBL curriculum. The purpose of this research was to evaluate the effects of pre-study examination results and peer evaluation ratings on learning outcomes.

Calcium responses to external mechanical stimuli in the multicellular stage of Dictyostelium discoideum.

Calcium acts as a second messenger to regulate many cellular functions, including cell motility. In Dictyostelium discoideum, the cytosolic calcium level oscillates synchronously, and calcium waves propagate through the cell population during the early stages of development, including aggregation. In the unicellular phase, the calcium response through Piezo channels also functions in mechanosensing.

Development of Low Molecular Weight Ligands for Integrin αβ.

We designed and synthesized non-peptide organic molecular ligands for integrin αβ. Candidate ligands featured amidino analog and carboxy groups as binding sites on either side of a spacer, which consisted of benzophenone or an analog, such as diphenyl sulfide, diphenyl sulfoxide, diphenyl sulfone, or diphenyl ether. Competitive binding assays to integrin αβ with respect to [I]echistatin were used to determine inhibitory activity of the synthetic ligands.

SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells.

Cancer invasion and metastasis are the major causes of cancer patient mortality. Various growth factors, including hepatocyte growth factor (HGF), are known to promote cancer invasion and metastasis, but the regulatory mechanisms involved are not fully understood. Here, we show that HGF-promoted migration and invasion of breast cancer cells are regulated by CUB domain-containing protein 1 (CDCP1), a transmembrane activator of SRC kinase.

Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias.

Signaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge about signaling bias at the GPCR level exists (preferential engagement of a specific transducer), little is known about the bias at the transducer level (different functions mediated by a single transducer), partly due to a poor understanding of GPCR kinase (GRK)-mediated GPCR phosphorylation. Here, we reveal a unique role of the Gq heterotrimer as a determinant for GRK-subtype selectivity that regulates subsequent β-arrestin conformation and function.

Structures and functions of the gut microbial lipidome.

Microbial lipids provide signals that are responsible for maintaining host health and controlling disease. The differences in the structures of microbial lipids have been shown to alter receptor selectivity and agonist/antagonist activity. Advanced lipidomics is an emerging field that helps to elucidate the complex bacterial lipid diversity.

Four- and two-armed hetero porphyrin dimers: their specific recognition and self-sorting behaviours.

In this study we self-assembled the four-armed porphyrin hetero dimer capsule Cap4, stabilized through amidinium-carboxylate salt bridges, in CHCl and CHCl. The dimer capsule Cap4 was kinetically and thermodynamically more stable than the corresponding two-armed dimer Cap2. The number of arms strongly influenced their recognition behaviour; guests possessing small aromatic faces (, 1,3,5-trinitrobenzene) preferred residing in the cavity of the two-armed capsule Cap2, rather than in Cap4, both thermodynamically and kinetically; in contrast, large aromatic guests (, 9,10-dibromoanthracene) were encapsulated predominantly by Cap4 because of favourable entropic effects.

Synthesis of a Mechanically Planar Chiral and Axially Chiral [2]Rotaxane.

In this study, we synthesized a [2]rotaxane that was both mechanically planar chiral and axially chiral, comprising a symmetrical bis-crown ether featuring a biphenyl moiety (as the macrocyclic component) and a symmetrical bis-ammonium salt (as the dumbbell-shaped component).