Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal ...relationship between the gut microbiota and AD pathophysiology is still elusive.
Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLP
) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.
Composition of the gut microbiota in ADLP
mice differed from that of healthy wild-type (WT) mice. Besides, ADLP
mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLP
mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLP
recipient mice.
These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLP
mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.
This paper proposes a resource-based task allocation algorithm for multi-robot systems. During mission operations, robots continuously consume their resources which must be refilled during their ...operations. Unlike other existing auction-based algorithms in which robots do not account for their resources in task allocations, the proposed algorithm considers the resources of the robots to generate their costs. In this algorithm, robots calculate the task performance estimation considering all the possibilities of visiting different combinations of refill stations based on their resource levels. This enables the robots to reduce unnecessary wastage of time and resources during the mission. The effectiveness of the proposed algorithm with respect to task completion time, resource consumption, and communication overhead is theoretically analyzed and is also demonstrated from the simulation of the delivery mission.
•A resource-based task allocation algorithm for multi-robot systems in a dynamic environment is proposed.•The proposed approach has four processes: winner update process, task trade process, bid generation process, and list update process.•The effectiveness of the proposed algorithm with respect to task completion time, resource consumption, and communication overhead is theoretically analyzed and is also demonstrated from the simulation of the delivery mission.
Additional surgeries for implantable biomedical devices are inevitable to replace discharged batteries, but repeated surgeries can be a risk to patients, causing bleeding, inflammation, and ...infection. Therefore, developing self‐powered implantable devices is essential to reduce the patient's physical/psychological pain and financial burden. Although wireless communication plays a critical role in implantable biomedical devices that contain the function of data transmitting, it has never been integrated with in vivo piezoelectric self‐powered system due to its high‐level power consumption (microwatt‐scale). Here, wireless communication, which is essential for a ubiquitous healthcare system, is successfully driven with in vivo energy harvesting enabled by high‐performance single‐crystalline (1 − x)Pb(Mg1/3Nb2/3)O3−(x)Pb(Zr,Ti)O3 (PMN‐PZT). The PMN‐PZT energy harvester generates an open‐circuit voltage of 17.8 V and a short‐circuit current of 1.74 µA from porcine heartbeats, which are greater by a factor of 4.45 and 17.5 than those of previously reported in vivo piezoelectric energy harvesting. The energy harvester exhibits excellent biocompatibility, which implies the possibility for applying the device to biomedical applications.
In vivo self‐powered wireless transmission using a flexible single‐crystalline piezoelectric energy harvester is demonstrated. The high‐performance energy harvester generates an output voltage of 17.8 V and a current of 1.75 µA from the contraction and relaxation motion of porcine heart. The energy from in vivo physiological motion enables self‐powered wireless transmission, thus realizing practical application in the ubiquitous healthcare system.
While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of ...endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.
C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.
HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice.
HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
Metabolomic approaches have been used to identify new diagnostic biomarkers for various types of cancers, including breast cancer. In this study, we aimed to identify potential biomarkers of breast ...cancer using plasma metabolic profiling. Furthermore, we analyzed whether these biomarkers had relationships with clinicopathological characteristics of breast cancer. Our study used two liquid chromatography-mass spectrometry sets: a discovery set (40 breast cancer patients and 30 healthy controls) and a validation set (30 breast cancer patients and 16 healthy controls). All breast cancer patients were randomly selected from among stage I-III patients who underwent surgery between 2011 and 2016. First, metabolites distinguishing cancer patients from healthy controls were identified in the discovery set. Then, consistent and reproducible metabolites were evaluated in terms of their utility as possible biomarkers of breast cancer. Receiver operating characteristic (ROC) analysis was applied to the discovery set, and ROC cut-off values for the identified metabolites derived therein were applied to the validation set to determine their diagnostic performance. Ultimately, four candidate biomarkers (L-octanoylcarnitine, 5-oxoproline, hypoxanthine, and docosahexaenoic acid) were identified. L-octanoylcarnitine showed the best diagnostic performance, with a 100.0% positive predictive value. Also, L-octanoylcarnitine levels differed according to tumor size and hormone receptor expression. The plasma metabolites identified in this study show potential as biomarkers allowing early diagnosis of breast cancer. However, the diagnostic performance of the metabolites needs to be confirmed in further studies with larger sample sizes.
Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production ...and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.
The gut dysbiosis by stressors such as immobilization deteriorates psychiatric disorders through microbiota-gut-brain axis activation. To understand whether probiotics could simultaneously alleviate ...anxiety/depression and colitis, we examined their effects on immobilization stress (IS)-induced anxiety/depression and colitis in mice. The probiotics
NK33 and
NK98 were isolated from healthy human feces. Mice with anxiety/depression and colitis were prepared by IS treatment. NK33 and NK98 potently suppressed NF-κB activation in lipopolysaccharide (LPS)-induced BV-2 cells. Treatment with NK33 and/or NK98, which were orally gavaged in mice before or after IS treatment, significantly suppressed the occurrence and development of anxiety/depression, infiltration of Iba1⁺ and LPS⁺/CD11b⁺ cells (activated microglia) into the hippocampus, and corticosterone, IL-6, and LPS levels in the blood. Furthermore, they induced hippocampal BDNF expression while NF-κB activation was suppressed. NK33 and/or NK98 treatments suppressed IS-induced colon shortening, myeloperoxidase activity, infiltration of CD11b⁺/CD11c⁺ cells, and IL-6 expression in the colon. Their treatments also suppressed the IS-induced fecal Proteobacteria population and excessive LPS production. They also induced BDNF expression in LPS-induced SH-SY5Y cells in vitro. In conclusion, NK33 and NK98 synergistically alleviated the occurrence and development of anxiety/depression and colitis through the regulation of gut immune responses and microbiota composition.
This article makes a case for the application of the conventional principal component analysis (PCA) unsupervised algorithm by modifying it with embedded high dimensional layers to achieve ...simultaneous and proportional intention estimation of individual fingers of the human body using surface electromyography (sEMG). Due to its linear nature, PCA in its original form is unfit for estimating intricate movements like individual fingers of the human hand. Hence, the PCA algorithm was improved using the application of nonlinear embedding of the original electromyography (EMG) data into a higher dimensional feature space. These embedding functions were used in single and multiple layers with their mapping functions evaluated from the PCA algorithm. The resulting algorithms from the application of these embedding functions are called nonlinear PCA (NLPCA) and multilayer NLPCA (ML-NLPCA). We compare these algorithms with the unsupervised algorithms of nonnegative matrix factorization (NMF), NMF with Hadamard product (NMF-HP), kernel NMF (kNMF), and kernel NMF-HP (kNMF-HP) from previous studies to draw comparisons in making our case. The models for each finger are trained blindly without any output values by the unsupervised algorithms to solve the individual finger estimation problem using an in- house eight-channel EMG acquisition system. It will be seen that ML-NLPCA produces the most effective results to reflect the movement of a human hand by generating simultaneous and proportional control (SPC) commands using a robot hand.
Background
Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been ...completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs.
Methods
Peripheral counts of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti‐IL‐33/TSLP antibody were tested.
Results
The numbers of EET+ eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these two cells (r = .539, P < .001). When mice were injected with EETs, we observed significant increases in epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL‐5‐ or IL‐13‐producing ILC2s in the lungs. When Rag1−/− mice receiving ILC2s were treated with EETs, increased AHR and IL‐5/IL‐13 levels in BALF were noted, which were effectively suppressed by anti‐IL‐33 or anti‐TSLP antibody.
Conclusion
EETs could enhance innate and type 2 immune responses in SA, in which epithelium‐targeting biologics (anti‐IL‐33/TSLP antibody) may have a potential benefit.
The numbers of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) are significantly elevated in severe asthma. EETs treatment in mice induces significant increase of epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid. EETs activate IL‐5 or IL‐13‐producing ILC2s through stimulating airway epithelium.Abbreviations: EETs, Eosinophil extracellular traps; TSLP, Thymic stromal lymphopoietin
To understand the role of commensal gut bacteria on the progression of cognitive decline in Alzheimer's disease via the microbiota-gut-brain axis, we isolated anti-inflammatory Bifidobacterium longum ...(NK46) from human gut microbiota, which potently inhibited gut microbiota endotoxin production and suppressed NF-κB activation in lipopolysaccharide (LPS)-stimulated BV-2 cells, and examined whether NK46 could simultaneously alleviate gut dysbiosis and cognitive decline in male 5xFAD-transgenic (5XFAD-Tg, 6 months-old) and aged (18 months-old) mice. Oral administration of NK46 (1 × 10
CFU/mouse/day for 1 and 2 months in aged and Tg mice, respectively) shifted gut microbiota composition, particularly Proteobacteria, reduced fecal and blood LPS levels, suppressed NF-κB activation and TNF-α expression, and increased tight junction protein expression in the colon of 5XFAD-Tg and aged mice. NK46 treatment also alleviated cognitive decline in 5XFAD-Tg and aged mice. Furthermore, NK46 treatment suppressed amyloid-β, β/γ-secretases, and caspase-3 expression and amyloid-β accumulation in the hippocampus of 5XFAD-Tg mice. NK46 treatment also reduced Iba1
, LPS
/CD11b
, and caspase-3
/NeuN
cell populations and suppressed NF-κB activation in the hippocampus of 5XFAD-Tg and aged mice, while BDNF expression was increased. These findings suggest that the suppression of gut dysbiosis and LPS production by NK46 can mitigate cognitive decline through the regulation of microbiota LPS-mediated NF-κB activation.
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