Pneumatic tactile stimulus delivery system for studying brain responses evoked by active finger touch with fMRI.

BACKGROUND: Primates use their hands to actively touch objects and collect information. To study tactile information processing, it is important for participants to experience tactile stimuli through active touch while monitoring brain activities. NEW METHOD: Here, we developed a pneumatic tactile stimulus delivery system (pTDS) that delivers various tactile stimuli on a programmed schedule and allows voluntary finger touches during MRI scanning. The pTDS uses a pneumatic actuator to move tactile stimuli and place them in a finger hole. A photosensor detects the time when an index finger touches a tactile stimulus, enabling the analysis of the touch-elicited brain responses. RESULTS: We examined brain responses while the participants actively touched braille objects presented by the pTDS. BOLD responses during tactile perception were significantly stronger in a finger touch area of the contralateral somatosensory cortex compared with that of visual perception. CONCLUSION: The pTDS enables MR studies of brain mechanisms for tactile processes through natural finger touch.

Antimicrobial activity of Limosilactobacillus fermentum strains isolated from the human oral cavity against Streptococcus mutans.

Oral probiotics have been recently gaining much attention owing to their potential to inhibit the progression of dental caries by controlling the cariogenic effects of Streptococcus mutans. We isolated and genotypically identified 77 lactic acid bacteria including 12 Limosilactobacillus fermentum probiotic candidates from the oral cavity of healthy volunteers. Among the 12 L. fermentum isolates, nine isolates effectively inhibited the growth of S. mutans via hydrogen peroxide (H2O2) production. The others neither suppressed the growth of S. mutans nor produced H2O2. Eight out of the nine H2O2-producing L. fermentum isolates exhibited strong adherence to oral epithelial KB cells while inhibiting the adherence of S. mutans to KB cells. The eight H2O2-producing isolates were neither haemolytic based on a blood-agar test, cytotoxic according to lactate dehydrogenase assay, nor resistant to eight antibiotics represented by the European Food Safety Authority guideline, indicating that the isolates have potential to suppress the cariogenesis driven by S. mutans while providing general probiotic benefits.

Where Do CABs Exist? Verification of a specific region containing concave Actin Bundles (CABs) in a 3-Dimensional confocal image.

CABs (Concave Actin Bundles) are oriented against the scaffold transversally in a manner different from traditional longitudinal F-actin bundles. CABs are present in a specific area, and do not exist in random areas. Biologically, CABs are developed to attach cells to fibers firmly so that CABs are found near cells. Based on this knowledge, we closely examined 3D confocal microcopy images containing fiber scaffolds, actin, and cells. Then, we assumed that the areas containing high values of compactness of fiber, compactness of actin, and density of cells would have many numbers of CABs.In this research, we wanted to prove this assumption. We first incorporated a two-point correlation function to define a measure of compactness. Then, we used the Bayes' theorem to prove the above assumption. As the assumption, our results verified that CABs exist in an area of high compactness of a fiber network, high compactness of actin distribution, and high density of cells. Thus, we concluded that CABs are developed to attach cells to a fibrillar scaffold firmly. This finding may be further verified mathematically in future studies.

Complete Genome Sequence of Hydrogen Peroxide-Producing Limosilactobacillus fermentum DM072 Isolated from the Human Oral Cavity.

The complete genome of hydrogen peroxide (H2O2)-producing Limosilactobacillus fermentum strain DM072, isolated from the oral cavity of healthy volunteers in South Korea, was sequenced by long-read sequencing and was subsequently corroborated by short-read sequencing. The genome comprises one circular chromosome and one plasmid and lacks antimicrobial resistance genes.

Complete Genome Sequence of Lacticaseibacillus rhamnosus DM065, Isolated from the Human Oral Cavity.

The 3.0-Mb complete genome of Lacticaseibacillus rhamnosus strain DM065, which was isolated from the oral cavity of healthy volunteers in South Korea, was sequenced using a combination of PacBio and Illumina technologies. The genome consists of one circular chromosome and two plasmids and lacks antimicrobial resistance genes.

The role of immunomodulatory metabolites in shaping the inflammatory response of macrophages.

Macrophage activation has long been implicated in a myriad of human pathophysiology, particularly in the context of the dysregulated capacities of an unleashing intracellular or/and extracellular inflammatory response. A growing number of studies have functionally coupled the macrophages' inflammatory capacities with dynamic metabolic reprogramming which occurs during activation, albeit the results have been mostly interpreted through classic metabolism point of view; macrophages take advantage of the rewired metabolism as a source of energy and for biosynthetic precursors. However, a specific subset of metabolic products, namely immune-modulatory metabolites, has recently emerged as significant regulatory signals which control inflammatory responses in macrophages and the relevant extracellular milieu. In this review, we introduce recently highlighted immuno-modulatory metabolites, with the aim of understanding their physiological and pathological relevance in the macrophage inflammatory response. [BMB Reports 2022; 55(11): 519-527].

Whole-Genome Sequence of Limosilactobacillus fermentum Strain DM075, Isolated from the Human Oral Cavity.

Here, we report the complete genome sequence of nitric oxide (NO)-producing Limosilactobacillus fermentum strain DM075, which was isolated from human tongue coating samples from healthy donors in South Korea. The complete genome sequence of DM075 comprises a single circular 2,204,022-bp genome, with a GC content of 51.0%, and lacks antimicrobial resistance genes.

Complete Genome Sequence of Lactiplantibacillus plantarum Strain DM083 Isolated from Human Tongue Coating.

We isolated Lactiplantibacillus plantarum DM083 from the human tongue coating to establish a strain library for oral probiotics. It has a single circular 3,197,299 bp chromosome with a guanine-cytosine (GC) content of 44.6% without plasmids. Importantly, the genome is devoid of the antimicrobial resistance gene, satisfying the minimum safety requirement for probiotics.

Conditioned media derived from human fetal progenitor cells improves skin regeneration in burn wound healing.

Stem cells are known to have excellent regenerative ability, which is primarily facilitated by indirect paracrine factors, rather than via direct cell replacement. The regenerative process is mediated by the release of extracellular matrix molecules, cytokines, and growth factors, which are also present in the media during cultivation. Herein, we aimed to demonstrate the functionality of key factors and mechanisms in skin regeneration through the analysis of conditioned media derived from fetal stem cells. A series of processes, including 3D pellet cultures, filtration and lyophilization is developed to fabricate human fetal cartilage-derived progenitor cells-conditioned media (hFCPCs-CM) and its useful properties are compared with those of human bone marrow-derived MSCs-conditioned media (hBMSCs-CM) in terms of biochemical characterization, and in vitro studies of fibroblast behavior, macrophage polarization, and burn wound healing. The hFCPCs-CM show to be devoid of cellular components but to contain large amounts of total protein, collagen, glycosaminoglycans, and growth factors, including IGFBP-2, IGFBP-6, HGF, VEGF, TGF ß3, and M-CSF, and contain a specific protein, collagen alpha-1(XIV) compare with hBMSCs-CM. The therapeutic potential of hFCPCs-CM observes to be better than that of hBMSCs-CM in the viability, proliferation, and migration of fibroblasts, and M2 macrophage polarization in vitro, and efficient acceleration of wound healing and minimization of scar formation in third-degree burn wounds in a rat model. The current study shows the potential therapeutic effect of hFCPCs and provides a rationale for using the secretome released from fetal progenitor cells to promote the regeneration of skin tissues, both quantitatively and qualitatively. The ready-to-use product of human fetal cartilage-derived progenitor cells-conditioned media (hFCPCs-CM) are fabricated via a series of techniques, including a 3D culture of hFCPCs, filtration using a 3.5 kDa cutoff dialysis membrane, and lyophilization of the CM. hFCPCs-CM contains many ECM molecules and biomolecules that improves wound healing through efficient acceleration of M2 macrophage polarization and reduction of scar formation.

Leaky Gum: The Revisited Origin of Systemic Diseases.

The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts but also to the many remote organs. Oral microbiota, travelling to the end of the intestine and circulating in our bodies through blood vessels, not only affect a gut microbiome profile but also lead to many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of "leaky gum", as an analogy of "leaky gut", to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is, thus, vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by the natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade the human body, making the leaky gum just as important as, or even more important than, the leaky gut.

Topographic Relationships among Deep Optic Nerve Head Parameters in Patients with Primary Open-Angle Glaucoma.

PURPOSE: To investigate the topographic relationships among the deep optic nerve head (ONH) parameters representing myopic axial elongation or changes in the lamina cribrosa (LC) in patients with primary open-angle glaucoma (POAG). METHODS: Among patients with POAG who visited the clinic between January 2015 and March 2017, the following deep ONH parameters were measured using spectral-domain optical coherence tomography (SD-OCT): externally oblique border tissue (EOBT) length, ONH tilt angle, optic canal (OC) obliqueness, and anterior LC insertion depth (ALID). In addition, the angular locations of the maximal value of each parameter were measured. We analyzed the correlations between the parameters, correlations with axial length (AL), and the spatial correspondence with glaucomatous ONH damage. RESULTS: A total of 100 eyes with POAG were included in the analysis. The EOBT length, ONH tilt angle, and OC obliqueness were correlated with each other and with AL, whereas ALID showed less correlation with the other parameters and AL. The angular location where the three AL-related parameters had maximum values was also correlated with the predominant region of the glaucomatous ONH damage, while the angular location of the deepest ALID showed less correlation. CONCLUSIONS: Among the deep ONH parameters, the AL-related parameters EOBT length, ONH tilt angle, and OC obliqueness showed strong spatial correspondence with glaucomatous ONH damage, whereas the LC-related parameter ALID was less correlated with both AL and the region with glaucomatous ONH damage. Further studies are needed to determine how these differences affect glaucomatous ONH change.

Factors Associated with Increased Neuroretinal Rim Thickness Measured Based on Bruch's Membrane Opening-Minimum Rim Width after Trabeculectomy.

PURPOSE: To investigate the factors associated with an increase in the neuroretinal rim (NRR) thickness measured based on Bruch's membrane opening-minimum rim width (BMO-MRW) after trabeculectomy in patients with primary open-angle glaucoma (POAG). METHODS: We analyzed the BMO-MRW using spectral-domain optical coherence tomography (SD-OCT) of patients with POAG who underwent a trabeculectomy for uncontrolled intraocular pressure (IOP) despite maximal IOP reduction treatment. The BMO-MRW was measured before and after trabeculectomy in patients with POAG. Demographic and systemic factors, ocular factors, pre- and post-operative IOP, and visual field parameters were collected, together with SD-OCT measurements. A regression analysis was performed to investigate the factors that affected the change in the BMO-MRW after the trabeculectomy. RESULTS: Forty-four eyes of 44 patients were included in the analysis. The IOP significantly decreased from a preoperative 27.0 mmHg to a postoperative 10.5 mmHg. The mean interval between the trabeculectomy and the date of post-operative SD-OCT measurement was 3.3 months. The global and sectoral BMO-MRW significantly increased after trabeculectomy, whereas the peripapillary retinal nerve fiber layer thickness did not show a difference between before and after the trabeculectomy. Younger age and a greater reduction in the IOP after the trabeculectomy were significantly associated with the increase in the BMO-MRW after trabeculectomy. CONCLUSIONS: The NRR thickness measured based on the BMO-MRW increased with decreasing IOP after trabeculectomy, and the increase in the BMO-MRW was associated with the young age of the patients and greater reduction in the IOP after trabeculectomy. Biomechanically, these suggest that the NRR comprises cells and substances that sensitively respond to changes in the IOP and age.

Bacteria Make a Living Breathing the Nitroheterocyclic Insensitive Munitions Compound 3-Nitro-1,2,4-triazol-5-one (NTO).

The nitroheterocyclic 3-nitro-1,2,4-triazol-5-one (NTO) is an ingredient of insensitive explosives increasingly used by the military, becoming an emergent environmental pollutant. Cometabolic biotransformation of NTO occurs in mixed microbial cultures in soils and sludges with excess electron-donating substrates. Herein, we present the unusual energy-yielding metabolic process of NTO respiration, in which the NTO reduction to 3-amino-1,2,4-triazol-5-one (ATO) is linked to the anoxic acetate oxidation to CO2 by a culture enriched from municipal anaerobic digester sludge. Cell growth was observed simultaneously with NTO reduction, whereas the culture was unable to grow in the presence of acetate only. Extremely low concentrations (0.06 mg L-1) of the uncoupler carbonyl cyanide m-chlorophenyl hydrazone inhibited NTO reduction, indicating that the process was linked to respiration. The ultimate evidence of NTO respiration was adenosine triphosphate production due to simultaneous exposure to NTO and acetate. Metagenome sequencing revealed that the main microorganisms (and relative abundances) were Geobacter anodireducens (89.3%) and Thauera sp. (5.5%). This study is the first description of a nitroheterocyclic compound being reduced by anaerobic respiration, shedding light on creative microbial processes that enable bacteria to make a living reducing NTO.

Strong correspondence between prefrontal and visual representations during emotional perception.

Emotion is thought to cause focal enhancement or distortion of certain components of memory, indicating a complex property of emotional modulation on memory rather than simple enhancement. However, the neural basis for detailed modulation of emotional memory contents has remained unclear. Here has been shown that the information processing of the prefrontal cortex differentially affects sensory representations during experience of emotional information compared with neutral information, using functional magnetic resonance imaging (fMRI). It was found that during perception of emotional pictures, information representation in primary visual cortex (V1) significantly corresponded with the representations in dorsolateral prefrontal cortex (dlPFC). This correspondence was not observed for neutral pictures. Furthermore, participants with greater correspondence between visual and prefrontal representations showed better memory for high-level semantic components but not for low-level visual components of emotional stimuli. These results suggest that sensory representation during experience of emotional stimuli, compared with neutral stimuli, is more directly influenced by internally generated higher-order information from the prefrontal cortex.

Quantification of nosZ genes and transcripts in activated sludge microbiomes with novel group-specific qPCR methods validated with metagenomic analyses.

Substantial N2O emission results from activated sludge nitrogen removal processes. N2O-reducing organisms possessing NosZ-type N2O reductases have been recognized to play crucial roles in suppressing emission of N2O produced in anoxic activated sludge via denitrification; however, which of the diverse nosZ-possessing organisms function as the major N2O sink in situ remains largely unknown. Here, nosZ genes and transcripts in wastewater microbiomes were analyzed with the group-specific qPCR assays designed de novo combining culture-based and computational approaches. A sewage sample was enriched in a batch reactor fed continuous stream of N2 containing 20-10,000 ppmv N2O with excess amount (10 mM) of acetate as the source of carbon and electrons, where 14 genera of potential N2O-reducers were identified. All available amino acid sequences of NosZ affiliated to these taxa were grouped into five subgroups (two clade I and three clade II groups), and primers/probe sets exclusively and comprehensively targeting the subgroups were designed and validated with in silico PCR. Four distinct activated sludge samples from three different wastewater treatment plants in Korea were analyzed with the qPCR assays and the results were validated with the shotgun metagenome analysis results. With these group-specific qPCR assays, the nosZ genes and transcripts of six additional activated sludge samples were analyzed and the results of the analyses clearly indicated the dominance of two clade II nosZ subgroups (Flavobacterium-like and Dechloromonas-like) among both nosZ gene and transcript pools.

Antarctic tundra soil metagenome as useful natural resources of cold-active lignocelluolytic enzymes.

Lignocellulose composed of complex carbohydrates and aromatic heteropolymers is one of the principal materials for the production of renewable biofuels. Lignocellulose-degrading genes from cold-adapted bacteria have a potential to increase the productivity of biological treatment of lignocellulose biomass by providing a broad range of treatment temperatures. Antarctic soil metagenomes allow to access novel genes encoding for the cold-active lignocellulose-degrading enzymes, for biotechnological and industrial applications. Here, we investigated the metagenome targeting cold-adapted microbes in Antarctic organic matter-rich soil (KS 2-1) to mine lignolytic and celluloytic enzymes by performing single molecule, real-time metagenomic (SMRT) sequencing. In the assembled Antarctic metagenomic contigs with relative long reads, we found that 162 (1.42%) of total 11,436 genes were annotated as carbohydrate-active enzymes (CAZy). Actinobacteria, the dominant phylum in this soil's metagenome, possessed most of candidates of lignocellulose catabolic genes like glycoside hydrolase families (GH13, GH26, and GH5) and auxiliary activity families (AA7 and AA3). The predicted lignocellulose degradation pathways in Antarctic soil metagenome showed synergistic role of various CAZyme harboring bacterial genera including Streptomyces, Streptosporangium, and Amycolatopsis. From phylogenetic relationships with cellular and environmental enzymes, several genes having potential for participating in overall lignocellulose degradation were also found. The results indicated the presence of lignocellulose-degrading bacteria in Antarctic tundra soil and the potential benefits of the lignocelluolytic enzymes as candidates for cold-active enzymes which will be used for the future biofuel-production industry.

Development and Evaluation of a Novel Passive Wrist Bilateral Rehabilitation Device paired with Virtual Reality: A Feasibility Study.

This paper introduces a novel passive wrist bilateral rehabilitation device coupled with a new Virtual Reality (VR) platform. This is the first work to have adapted three-link coaxial spherical parallel manipulator (SPM) to wrist rehabilitation. The device comprises a coaxial SPM and cross-connected cable system. The coaxial SPM facilitates 3 degrees of freedom (DOFs) spherical wrist orientation and singularity-free motion within its workspace. The cross-connected cable system enables bilateral symmetrical exercises in passive mode training. A VR platform with activities of daily living (ADL) task was developed and coupled with the device to increase the adherence of the users to the device. Experiments were conducted with fifteen healthy right-handed individuals with no history of wrist or hand injury to evaluate the feasibility of the system for providing passive bilateral training as well as the effectiveness of the VR platform. Subjects were asked to use their right arms to move the left arms passively through the device to perform four wrist movements, flexion, extension, radial deviation, and ulnar deviation. EMG activations on the left arm were observed when the right arm passively moved the left arm. The results showed that the device was capable of inducing the muscle activation of the left arm and the VR platform increased the motivation to continue the exercises. This demonstrates that this study can serve as the fundamental for larger clinical trials.

Generalization of Conscious Fear Is Positively Correlated with Anxiety, but Not with Depression.

Generalization of learned fear has been considered to be critical for our survival. Patients with anxiety problems show overgeneralization of learned fear, as reflected by defensive physiological responses to harmless stimuli. Together with these physiological responses, conscious feeling of fear is a seminal part of emotional process that is directly related to the suffering of anxiety patients. However, the effect of anxiety on the generalization of conscious feeling remains unclear. We thus focused on the question whether the generalization of conscious feeling of fear depends on individual anxiety level in nonpatient participants. To address this question, we developed a fear generalization paradigm using natural scene images. We found that subjective feeling of fear was generalized to similar stimuli with the conditioned stimuli (CS), and that this generalization of conscious fear was positively correlated with the level of individual anxiety. Anxiety and depression frequently co-occur, but the individual depression level was not correlated with the fear generalization. These suggest that individual anxiety level mainly affects the generalization of conscious fear.

Methanobactin from Methylosinus trichosporium OB3b inhibits N2O reduction in denitrifiers.

Methanotrophs synthesize methanobactin, a secondary metabolite that binds copper with an unprecedentedly high affinity. Such a strategy may provide methanotrophs a "copper monopoly" that can inhibit the activity of copper-containing enzymes of other microbes, e.g., copper-dependent N2O reductases. Here, we show that methanobactin from Methylosinus trichosporium OB3b inhibited N2O reduction in denitrifiers. When Pseudomonas stutzeri DCP-Ps1 was incubated in cocultures with M. trichosporium OB3b or with purified methanobactin from M. trichosporium OB3b, stoichiometric N2O production was observed from NO3- reduction, whereas no significant N2O accumulation was observed in cocultures with a mutant defective in methanobactin production. Copper uptake by P. stutzeri DCP-Ps1 was inhibited by the presence of purified methanobactin, leading to a significant downregulation of nosZ transcription. Similar findings were observed with three other denitrifier strains. These results suggest that in situ stimulation of methanotrophs can inadvertently increase N2O emissions, with the potential for increasing net greenhouse gas emissions.

pH Control Enables Simultaneous Enhancement of Nitrogen Retention and N2O Reduction in Shewanella loihica Strain PV-4.

pH has been recognized as one of the key environmental parameters with significant impacts on the nitrogen cycle in the environment. In this study, the effects of pH on NO3-/NO2- fate and N2O emission were examined with Shewanella loihica strain PV-4, an organism with complete denitrification and respiratory ammonification pathways. Strain PV-4 was incubated at varying pH with lactate as the electron donor and NO3-/NO2- and N2O as the electron acceptors. When incubated with NO3- and N2O at pH 6.0, transient accumulation of N2O was observed and no significant NH4+ production was observed. At pH 7.0 and 8.0, strain PV-4 served as a N2O sink, as N2O concentration decreased consistently without accumulation. Respiratory ammonification was upregulated in the experiments performed at these higher pH values. When NO2- was used in place of NO3-, neither growth nor NO2- reduction was observed at pH 6.0. NH4+ was the exclusive product from NO2- reduction at both pH 7.0 and 8.0 and neither production nor consumption of N2O was observed, suggesting that NO2- regulation superseded pH effects on the nitrogen-oxide dissimilation reactions. When NO3- was the electron acceptor, nirK transcription was significantly upregulated upon cultivation at pH 6.0, while nrfA transcription was significantly upregulated at pH 8.0. The highest level of nosZ transcription was observed at pH 6.0 and the lowest at pH 8.0. With NO2- as the electron acceptor, transcription profiles of nirK, nrfA, and nosZ were statistically indistinguishable between pH 7.0 and 8.0. The transcriptions of nirK and nosZ were severely downregulated regardless of pH. These observations suggested that the kinetic imbalance between N2O production and consumption, but neither decrease in expression nor activity of NosZ, was the major cause of N2O accumulation at pH 6.0. The findings also suggest that simultaneous enhancement of nitrogen retention and N2O emission reduction may be feasible through pH modulation, but only in environments where C:N or NO2-:NO3- ratio does not exhibit overarching control over the NO3-/NO2- reduction pathways.