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The occurrence of multidrug-resistant Acinetobacter baumannii (MDRA) has increased rapidly and is associated with severe nosocomial infections. MDRA has emerged in the hospital setting and has evolved into extensively drug-resistant A. baumannii (XDRA). A clinical XDRA isolate obtained from a hospitalised patient in 2016 was evaluated for antibiotic susceptibility and whole-genome sequence. The XDRA isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, fosfomycin, fluoroquinolones, tetracyclines, tigecycline, and trimethoprim-sulfamethoxazole. The isolate harboured abaF, ant(3″)-II-c, aph(3″)-Ib, aph(6)-Id, armA, blaADC-73, blaTEM-1, blaOXA-66, blaOXA-23, mphE, msrE and tet(B). Quinolone resistance was associated with mutations gyrA S81L and parC S84L. Tigecycline resistance was associated with a mutation in adeS. The isolate belonged to Oxford and Pasteur scheme sequence type 1050 and 2, respectively, and harboured a conjugative plasmid containing the aminoglycoside resistance transposon TnaphA6. Our study demonstrates that the isolate is closely related to a recent MDRA identified in Australia and the USA, in which a similar conjugative plasmid is not observed. Although the MDRA in Australia caused an outbreak, our hospital's surveillance protocol managed to prevent a further outbreak. Our finding suggests that this XDRA isolate is of concern in hospital and community care settings. The gpi allele could be a marker for discriminating this isolate from clonal complex 92 isolates.

Objectives: To assess the vitamin D status in postmenopausal women with osteoporotic fractures, determine its concentration by fracture site at the clinical setting, and compare the proportion of vitamin D deficiency with that reported in literature. Methods: The prospective study included 317 postmenopausal women with osteoporotic fractures who were treated consecutively from 2016 to 2018. After obtaining informed consent for participation in the seamless treatment of osteoporosis against fractures study, which is our initiative to prevent secondary osteoporotic fractures, we registered the patients, examined bone mineral density (BMD) at the unfractured femoral neck and lumbar spine, serum 25-hydroxyvitamin D (25(OH)D) concentration, blood chemistry, and bone turnover markers. Results: The mean age of the patients was 80.7 years. Moreover, 78% of patients of all fractures had 25(OH)D concentration

The quantitative modeling of semantic representations in the brain plays a key role in understanding the neural basis of semantic processing. Previous studies have demonstrated that word vectors, which were originally developed for use in the field of natural language processing, provide a powerful tool for such quantitative modeling. However, whether semantic representations in the brain revealed by the word vector-based models actually capture our perception of semantic information remains unclear, as there has been no study explicitly examining the behavioral correlates of the modeled brain semantic representations. To address this issue, we compared the semantic structure of nouns and adjectives in the brain estimated from word vector-based brain models with that evaluated from human behavior. The brain models were constructed using voxelwise modeling to predict the functional magnetic resonance imaging (fMRI) response to natural movies from semantic contents in each movie scene through a word vector space. The semantic dissimilarity of brain word representations was then evaluated using the brain models. Meanwhile, data on human behavior reflecting the perception of semantic dissimilarity between words were collected in psychological experiments. We found a significant correlation between brain model- and behavior-derived semantic dissimilarities of words. This finding suggests that semantic representations in the brain modeled via word vectors appropriately capture our perception of word meanings.

The relational network of people (RNP) model has been attracting the interest of not only researchers but also industrial engineers. RNP can be constructed from friend lists in online social networking services (SNSs) and from inter-contact logs between individuals. One of the killer applications of RNP is the prediction of user demands, which is key to maximizing user satisfaction in content delivery services such as video streaming and video advertising. It is well known that an RNP representing social closeness between individuals (a so-called social network) can estimate user preferences simply, as we expect that people close to each other will have similar preferences. However, although there are many metrics that enable the social closeness between individuals to be measured, it is unclear which metric is best suited for individual services. Therefore, this paper introduces a new approach based on brain imaging. Brain imaging using functional Magnetic Resonance Imaging (fMRI) is powerful because it enables us to directly observe how a video content stimulates the brains of individual people. We propose a brain imaging-based RNP that represents the similarity of video-evoked brain activities between people as a network graph. We show an application scenario featuring predictive content delivery using the proposed RNP in which, when a user shows interest in a video content in some way, other users close to him or her can be expected to also be interested in it because their brain activities are correlated. Through numerical evaluation using multiple real datasets obtained by fMRI, we demonstrate that the proposed RNP is generalizable across brain imaging results for different sets of video content, thus suggesting that brain imaging data can be used to robustly generate RNP for utilization as a powerful tool for estimating user preferences.

Lean premixed combustion can be expected to reduce the high-temperature area and NOx emission. However, it has a risk of flashback due to flame propagation. It can be thought to modulate the gas swirl intensity to prevent flashback and to stabilize combustion. In this research, we developed time-variable-angle swirl vanes which had 56 mm of the inner diameter, 70 mm of the outer diameter and consisted of 36 vanes, each vane was directly connected to a stepping motor, and the swirl intensity could be changed periodically by keeping the constant air ratio and flow rate. We confirmed the periodical movement of the swirl vane angle using a high-speed camera. The flame position could be made reciprocating move upstream and downstream by the periodic change of the swirl vane angle. The upstream direction flow at the tip of the flame appeared when the flame moved in the upstream direction with increasing vane angle and the downstream direction flow appeared when that moved in the downstream direction with decreasing the vane angle. When the flame propagation was changed from upstream direction to downstream, the upstream direction flow near the flame tip was weakened. In advance of changing the flame propagation from upstream direction to downstream, the axial velocity near the flame tip changed from decreasing to increasing.

Acinetobacter baumannii causes nosocomial infections due to its multidrug resistance and high environmental adaptability. Colistin is a polypeptide antibacterial agent that targets lipopolysaccharide (LPS) and is currently used to control serious multidrug-resistant Gram-negative bacterial infections, including those caused by A. baumannii. However, A. baumannii may acquire colistin resistance by losing their LPS. In mouse models, LPS-deficient A. baumannii have attenuated virulence. Nevertheless, the mechanism through which the pathogen is cleared by host immune cells is unknown. Here, we established colistin-resistant A. baumannii strains and analyzed possible mechanisms through which they are cleared by neutrophils. Colistin-resistant, LPS-deficient strains harbor mutations or insertion sequence (IS) in lpx genes, and introduction of intact lpx genes restored LPS deficiency. Analysis of interactions between these strains and neutrophils revealed that compared with wild type, LPS-deficient A. baumannii only weakly stimulated neutrophils, with consequent reduced levels of reactive oxygen species (ROS) and inflammatory cytokine production. Nonetheless, neutrophils preferentially killed LPS-deficient A. baumannii compared to wild-type strains. Moreover, LPS-deficient A. baumannii strains presented with increased sensitivities to antibacterial lysozyme and lactoferrin. We revealed that neutrophil-secreted lysozyme was the antimicrobial factor during clearance of LPS-deficient A. baumannii strains. These findings may inform the development of targeted therapeutics aimed to treat multidrug-resistant infections in immunocompromised patients who are unable to mount an appropriate cell-mediated immune response.

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in healthcare settings worldwide. Objectives: We evaluated the presence of carbapenemase genes in CPE in a tertiary care university hospital in Tokyo, Japan. Methods: Carbapenem-resistant clinical isolates were collected in 2018 at Teikyo University Hospital (Tokyo, Japan). Bacterial species were identified using MALDI-TOF MS. Carbapenemase production was evaluated using a carbapenemase inactivation method. The presence of carbapenemase genes was confirmed by multiplex PCR and DNA sequencing. Results: Four CPE isolates were identified: two Enterobacter cloacae complex strains and Klebsiella oxytoca and Klebsiella pneumoniae strains. Three of the isolates (E. cloacae complex and K. oxytoca) were IMP-1-type producers, including IMP-10 in their produced metallo-β-lactamase, and are epidemic in East Japan. The IMP-10-producing E. cloacae complex strain also produced CTX-M ESBL. The other CPE isolate (K. pneumoniae) is a VIM-1 producer. VIM-1-producing K. pneumoniae is epidemic in Europe, especially in Greece. Accordingly, the VIM-1 producer was isolated from a patient with a medical history in Greece. Conclusions: This study revealed the emergence of E. cloacae complex co-producing IMP-1-type carbapenemase and CTX-M ESBL, and K. pneumoniae producing VIM-1 carbapenemase in clinical isolates in Japan. Metallo-β-lactamase was the most prevalent type of carbapenemase at Teikyo University Hospital, especially IMP-1-type carbapenemase. The detection of VIM-1-producing K. pneumoniae suggests that epidemic CPE from overseas can spread to countries with low CPE prevalence, such as Japan, highlighting the need for active surveillance.

Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

Acinetobacter baumannii is one of the most important nosocomial opportunistic pathogen worldwide. In addition, obesity has been associated with an increased risk of nosocomial infection, suggesting that there may be an association between A. baumannii and white adipose tissue. However, the effects of A. baumannii on adipocytes have not been well studied at the molecular level. Here, we investigated the potential role of A. baumannii-derived lipopolysaccharides (LPS) as signaling molecules that affect adipocyte functionality. We tested the effect of increasing concentrations of A. baumannii-derived LPS (10, 100, or 1000 ng/mL) on the 3T3-L1 adipocyte cell line. Exposure to LPS was found to increase the expression of several adipokines (e.g., MIP-2, MCP-1, TNF-α, IL-6, lipocalin-2, and FABP4) in 3T3-L1 adipocytes and significantly reduced the expression of leptin and adiponectin. The effects of A. baumannii-derived LPS on MIP-2 expression were similar in comparison with that of LPS prepared from Pseudomonas aeruginosa and Escherichia coli in our cell culture-based system. This study suggests that A. baumannii-derived LPS functions as a signaling molecule that impacts the inflammatory function of white adipose tissue on the level of gene expression.

Drug resistance in bacterial infections and cancers constitutes a major threat to human health. Treatments often include several interacting drugs, but even potent therapies can become ineffective in resistant mutants. Here, we simplify the picture of drug resistance by identifying scaling laws that unify the multidrug responses of drug-sensitive and -resistant cells. On the basis of these scaling relationships, we are able to infer the two-drug response of resistant mutants in previously unsampled regions of dosage space in clinically relevant microbes such as E. coli, E. faecalis, S. aureus, and S. cerevisiae as well as human non-small-cell lung cancer, melanoma, and breast cancer stem cells. Importantly, we find that scaling relations also apply across evolutionarily close strains. Finally, scaling allows one to rapidly identify new drug combinations and predict potent dosage regimes for targeting resistant mutants without any prior mechanistic knowledge about the specific resistance mechanism.

When viewing a painting, artists perceive more information from the painting on the basis of their experience and knowledge than art novices do. This difference can be reflected in eye scan paths during viewing of paintings. Distributions of scan paths of artists are different from those of novices even when the paintings contain no figurative object (i.e. abstract paintings). There are two possible explanations for this difference of scan paths. One is that artists have high sensitivity to high-level features such as textures and composition of colors and therefore their fixations are more driven by such features compared with novices. The other is that fixations of artists are more attracted by salient features than those of novices and the fixations are driven by low-level features. To test these, we measured eye fixations of artists and novices during the free viewing of various abstract paintings and compared the distribution of their fixations for each painting with a topological attentional map that quantifies the conspicuity of low-level features in the painting (i.e. saliency map). We found that the fixation distribution of artists was more distinguishable from the saliency map than that of novices. This difference indicates that fixations of artists are less driven by low-level features than those of novices. Our result suggests that artists may extract visual information from paintings based on high-level features. This ability of artists may be associated with artists' deep aesthetic appreciation of paintings.

Background: Lactobacillus paracasei strain KW3110 has been shown by in vitro cytokine secretion analysis to be a potent Th1 inducer and Th2 repressor. Oral administration of L. paracasei strain KW3110 also represses IgE elevation in the ovalbumin sensitized mouse allergy model. Methods: During pollen season from January to April in 2003, a daily dose of 4x1010 cfu L. paracasei strain KW3110 was fed for 12 weeks as a yogurt to 14 pollen allergy patients(mean age 39.0 years). A yogurt made with Lactobacillus delbrueckii strain B, shown to be a poor Th1 inducer and Th2 repressor in a former study, was also fed at a daily dose of 4x1010 cfu for 12 weeks to 14 pollen allergy patients(mean age, 39.0 years). Blood samples were collected every 4 weeks. Eosinophils, eosinophil cationic protein(ECP), non-specific serum IgE, cedar pollen specific serum IgE, and Th1/Th2 ratios were quantified. Results: Twelve weeks after ingestion of the yogurts, the group that was fed L. delbrueckii group showed significant reductions in the Th1/Th2 ratios between the first observation in January and last observation in April, representing the four month study period, due to increases in Th2 cells. Significant increases in ECP were also observed in the group fed L. delbrueckii between January and April. In contrast, the group fed L. paracasei had no significant changes in the ECP and Th1/Th2 ratios. Conclusions: Our results suggest that ingestion of the L. paracasei strain KW3110 is associated with both repression of Th2 cell generation and eosinophil activation. Our data point to the possibility that specific lactic acid bacteria may be useful for allergy therapy.

Neutrophils play a critical role in the innate immune response. Recently, a new neutrophilic biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. Neutrophils have been observed to release both lysosomal enzymes and their nuclear contents, including unfolded chromatin, which together trap and inactivate bacteria. The environment in tissues where neutrophils act is thought to be different from that of the blood serum. In this study, we assessed the effect of serum on NET formation. We found that neutrophils spontaneously form NETs in serum-free cultivation conditions at early times. These NETs functioned properly to trap bacteria. Furthermore, we demonstrated that reactive oxygen species play a critical role in the spontaneous formation of NETs. These results suggest that the serum condition must be considered in studies on neutrophils, including the formation and mechanism of action of NETs. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) have high immune system-stimulating activity and are considered beneficial for human health as probiotics in the gut. The innate immune system is highly conserved between mammals and insects. Microbe-associated molecular patterns (e.g., peptidoglycan and β-glucan) induce cytokinematuration, which, in silkworm larvae, leads to muscle contraction. The purpose of this study is to find a novel probiotic by using silkworm muscle contraction assay. In the present study, we isolated LAB derived from rice bran pickles. We selected highly active LAB to activate the innate immune system of the silkworm, which was assayed based on silkworm muscle contraction. Of various LAB, L. paraplantarum 11-1 strongly stimulated innate immunity in the silkworm, leading to stronger silkworm contraction than a dairy-based LAB. Silkworms fed a diet containing L. paraplantarum 11-1 exhibited tolerance against the pathogenicity of Pseudomonas aeruginosa. These findings suggest that L. paraplantarum 11-1 could be a useful probiotic for activating innate immunity. [ABSTRACT FROM AUTHOR]

We screened lactic acid bacteria that exhibited high innate immunity-stimulating activity by monitoring muscle contraction activity in silkworms. Heat-treated fractions of lactic acid bacteria, Leuconostoc carnosum #7-2, Leuconostoc gelidum #4-2, and Leuconostoc mesenteroides 8/11-3, had high (250-460 units/mg) innate immunity-stimulating activity. These lactic acid bacteria proliferated in milk to concentrations of 1 × 106 colony forming unit/mL. The present findings suggest that the silkworm muscle contraction assay is useful for screening lactic acid bacteria with high innate immunity-stimulating activity, and that the assay can be used for the production of fermented foods made from milk. [ABSTRACT FROM AUTHOR]

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD50) werecalculated for each compound. Acute oral LD50 values in mammals are listed in OECD guidelines and acute oral LD50 values in silkworms were determined in this study. R2 for the correlation between LD50 values in mammals and LD50 values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products. We selected a highly active LAB to activate the innate immunity in silkworm by using the silkworm muscle contraction assay, as well. The assay revealed that Lactococcus lactis 11/19-B1 was highly active on the stimulation of the innate immunity in silkworm. L. lactis 11/19-B1 solely fermented milk with casamino acid and glucose. This strain would be a starter strain to make yogurt. Compared to commercially available yogurt LAB, L. lactis 11/19-B1 has higher activity on silkworm contraction. Silkworm normally ingested an artificial diet mixed with L. lactis 11/19-B1 or a yogurt fermented with L. lactis 11/19-B1. Interestingly, silkworms that ingested the LAB showed tolerance against the pathogenicity of Pseudomonas aeruginosa. These data suggest that Lactococcus lactis 11/19-B1 would be expected to be useful for making yogurt and probiotics to activate innate immunity. [ABSTRACT FROM AUTHOR]

The neuronal processes that underlie visual searches can be divided into two stages: target discrimination and saccade preparation/generation. This predicts that the length of time of the prediscrimination stage varies according to the search difficulty across different stimulus conditions, whereas the length of the latter postdiscrimination stage is stimulus invariant. However, recent studies have suggested that the length of the postdiscrimination interval changes with different stimulus conditions. To address whether and how the visual stimulus affects determination of the postdiscrimination interval, we recorded singleneuron activity in the lateral intraparietal area (LIP) when monkeys (Macaca fuscata) performed a color-singleton search involving four stimulus conditions that differed regarding luminance (Bright vs. Dim) and target-distractor color similarity (Easy vs. Difficult). We specifically focused on comparing activities between the Bright-Difficult and Dim-Easy conditions, in which the visual stimuli were considerably different, but the mean reaction times were indistinguishable. This allowed us to examine the neuronal activity when the difference in the degree of search speed between different stimulus conditions was minimal. We found that not only prediscrimination but also postdiscrimination intervals varied across stimulus conditions: the postdiscrimination interval was longer in the Dim-Easy condition than in the Bright-Difficult condition. Further analysis revealed that the postdiscrimination interval might vary with stimulus luminance. A computer simulation using an accumulation-to-threshold model suggested that the luminance-related difference in visual response strength at discrimination time could be the cause of different postdiscrimination intervals. [ABSTRACT FROM AUTHOR]

Neurons in the lateral intraparietal area (LIP) are involved in signaling the location of behaviorally relevant objects during visual discrimination and working memory maintenance. Although previous studies have examined these cognitive processes separately, they often appear as inseparable sequential processes in real-life situations. Little is known about how the neural representation of the target location is altered when both cognitive processes are continuously required for executing a task. We investigated this issue by recording single-unit activity from LIP of monkeys performing a delayed-response visual search task in which they were required to discriminate the target from distractors in the stimulus period, remember the location at which the extinguished target had been presented in the delay period, and make a saccade to that location in the response period. Target-location signaling was assessed using response modulations contingent on whether the target location was inside or opposite the receptive field. Although the population-averaged response modulation was consistent and changed only slightly during a trial, the across-neuron pattern of response modulations showed a marked and abrupt change around 170 ms after stimulus offset due to concurrent changes in the response modulations of a subset of LIP neurons, which manifested heterogeneous patterns of activity changes during the task. Our findings suggest that target-location signaling by the across-neuron pattern of LIP activity discretely changes after the stimulus disappearance under conditions that continuously require visual discrimination and working memory to perform a single behavioral task. [ABSTRACT FROM AUTHOR]

During visual search, neurons in the lateral intraparietal area (LIP) discriminate the target from distractors by exhibiting stronger activation when the target appears within the receptive field than when it appears outside the receptive field. It is generally thought that such target-discriminative activity is produced by the combination of target-related facilitation and distractor-related suppression. However, little is known about how the target-discriminative activity is constituted by these two types of neural modulation. To address this issue, we recorded activity from LIP of monkeys performing a visual search task that consisted of target-present and target-absent trials. Monkeys had to make a saccade to a target in the target-present trials, whereas they had to maintain fixation in the target-absent trials, in which only distractors were presented. By introducing the activity from the latter trials as neutral activity, we were able to separate the target-discriminative activity into targetrelated elevation and distractor-related reduction components. We found that the target-discriminative activity of most LIP neurons consisted of the combination of target-related elevation and distractorrelated reduction or only target-related elevation. In contrast, targetdiscriminative activity composed of only distractor-related reduction was observed for very few neurons. We also found that, on average, target-related elevation was stronger and occurred earlier compared with distractor-related reduction. Finally, we consider possible underlying mechanisms, including lateral inhibitory interactions, responsible for target-discriminative activity in visual search. The present findings provide insight into how neuronal modulations shape targetdiscriminative activity during visual search. [ABSTRACT FROM AUTHOR]

Vegetables are eaten as part of a healthy diet throughout the world, and some are also applied topically as a traditional medicine. We evaluated the innate immunostimulating activities of hot water extracts of various vegetables using the silkworm muscle contraction assay system, and found that broccoli, Brassica oleracea var. italica, contains a strong innate immunostimulant. We purified the innate immunostimulant from broccoli, and characterized the chemical structure by chemical analyses and NMR spectroscopy. The innate immunostimulant comprised galacturonic acid, galactose, glucose, arabinose, and rhamnose, and had a pectic-like polysaccharide structure. To determine the structural motif involved in the innate immunostimulating activity, we modified the structure by chemical and enzymatic treatment, and found that the activity was attenuated by pectinase digestion. These findings suggest that a pectic-like polysaccharide purified from broccoli has innate immunestimulating activity, for which the polygalacturonic acid structure is necessary. [ABSTRACT FROM AUTHOR]

Leuconostoc carnosum #7-2, L. gelidum #4-2, and L. mesenteroides 8/11-3, which were isolated from fermented plant foods, are lactic acid bacteria. We previously reported that these bacteria are functional lactic acid bacteria whose innate immunity-stimulating activities are high based on a silkworm muscle contraction assay. The concentrations of these three lactic acid bacteria increased to more than 1 × 106 colony forming units (cfu)/mL in various vegetable and fruit juices when the pH values were appropriately adjusted. As the bacteria grew in the vegetable and fruit juices, the pH decreased and the concentrations of total sugars and glucose also decreased. These findings suggest that these functional lactic acid bacteria can be used to produce vegetable and fruit juices with reduced sugar levels, which is expected to be beneficial for human health. [ABSTRACT FROM AUTHOR]