Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. ...Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.
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•A strong correlation between epithelial adhesion and Th17 induction by SFB and EHEC•Twenty Th17-inducing strains isolated from human feces show epithelial-adhesive property•Bacterial adhesion elicits a Th17-inducing gene-expression program in epithelium
The adhesion of specific members of the gut microbiome to intestinal epithelial cells is found to be essential for the induction of Th17 cells, thus highlighting location as an additional layer of regulation for the adaptive immune system.
Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we ...investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA-microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA-microbiota relationships, which is an important step for developing strategies for modulating lifelong health.
Background:This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-4-(2-iodophenyl)piperidinocyclopentanol ...(OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5–6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area.Conclusions:The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion.
Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain ...poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications.
Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the ...tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.
We proposed a novel radiant floor cooling system using phase change materials (PCMs) with night ventilation in the hot and humid climate of Indonesia. This study aims to clarify the measures to ...ensure the thermal storage effect of the proposed cooling system during daytime for a naturally ventilated room within a relatively narrow diurnal temperature range, focusing mainly on the thermal properties of PCMs. We analyzed the relationship between the indoor vertical air temperature distributions and heat flows of the proposed system using an experimental building in Tangerang, Indonesia. The results confirmed that the thermal mass of PCMs and the cooling strategy for the floor structure at night strongly contributed to maintaining a low floor surface temperature during the subsequent daytime. Calm wind conditions and warm nocturnal ambient temperature, which was 0.7–3.2 °C lower than the set-point solidifying temperature and is common in the tropics, prevented PCMs from solidifying in case of natural ventilation for the underfloor space. In contrast, forced ventilation for the underfloor space attaching PCMs was effective in ensuring sufficient solidification. Furthermore, 95% of the thermal storage capacity of PCMs might be utilized when the ambient temperature was 2–3 °C higher than the set-point melting temperature during the daytime. The phase change temperature for PCMs can be determined based on the average ambient temperature, whereas a relatively wide diurnal ambient temperature range, at least 4.7 °C, was required to ensure the latent heat thermal storage effect caused by the supercooling.
•Latent heat thermal storage was influential in lowering floor surface temperature.•Forced ventilation ensured the sufficient solidification of PCMs at warm nights.•Diurnal temperature range at least 4.7 °C was required to ensure phase changes.
Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; n
= 13; n
= 83) from the Knight Alzheimer Disease Research Center (Knight ...ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), of which annual number has rapidly increased in Japan, and it can be divided into two categories based on the ...amino acid at position 233 in the Tax protein. Here, we conducted a nationwide surveillance of Japanese Black cattle between 2008 and 2021 in Japan. Among 237 tumor samples, 131 (55.3%) and 101 (42.6%) were harbored L233- and P233-Tax, respectively. Onset of EBL under the age of 3 years by L233-Tax-carrying BLV was frequently observed, especially in the animals born via embryo transfer. We also found that L233-Tax-carrying BLV was more prevalent in dairy areas than non-dairy areas. These findings give insight into prevention of EBL.
Abstract This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine ( m IBG) ...imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123 I- m IBG as a pretreatment screening for 131 I- m IBG therapy. Two expert reviewers evaluated WB-MRI, 123 I- m IBG images, and post-therapy 131 I- m IBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)—area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123 I- m IBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131 I- m IBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the m IBG images.
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