Milk cytokines play a vital role in mucosal immunity during infancy by supporting immune development and functions. Although the maternal background characteristics influence milk cytokines, changes ...in cytokine levels across generations remain unclear. Colostrum (C,
= 48) and mature milk (MM,
= 49) samples were collected from lactating Japanese women in 1989 (2727 samples) and 2013 (1408 samples). Milk cytokines were comprehensively measured using a suspension array and immunosorbent assays. The positive rates and cytokine concentrations were compared between the two generations using logistic and multiple regression analyses. Twenty-eight cytokines tested positive in all sample groups (1989-C, 1989-MM, 2013-C, and 2013-MM). The median osteopontin (OPN) level was significantly higher in the 1989-C group than in the 2013-C group (318.1 vs. 137.5 μg/mL;
= 0.0016) but did not differ between the MM groups. The median TGF-β1 level was significantly lower in the 1989-MM group than in the 2013-MM group (1056.2 vs. 1330.8 pg/mL;
= 0.008) but did not differ between the C groups. Most cytokines were comparable between generations, except for potential variation in the C-OPN and TGF-β1 levels. Milk cytokine secretion may reflect temporal changes in maternal background characteristics; however, the results from the analysis of 30-year-old samples may have influenced the milk cytokine levels. Further studies are needed with a larger number of milk samples collected from the same individuals at multiple time points over a wide lactation period, with detailed data on the maternal and infant background characteristics and diets.
A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer’s disease (AD), although sensitive detection of frontotemporal lobar degeneration ...(FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick’s disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.
•A new probe, PM-PBB3, captures pathological tau deposits in vivo with high contrast•PM-PBB3 allows an individual-based identification of AD and non-AD tauopathies•Autopsy assays of PET-scanned patients supported the in vivo performance of PM-PBB3
Tagai et al. developed a positron emission tomography probe, 18F-PM-PBB3, for tau deposits in Alzheimer’s and non-Alzheimer’s disease tauopathies. This probe was demonstrated to enable individual- and pathology-based diagnosis, differentiation, and staging of these disorders in addition to translational research and development on tauopathies from mouse models to humans.
About 12-week-old napier grass Pennisetum purpureum Schumach) and 10-month-old Leucaena (Leucaenaleucocephala (Lam.) de Wit.) both from a naturalized field and chopped to about 3.5 cm were used. The ...grass andlegume were combined in a grass:legume ratio of 7:3. Therewere five treatments viz., napier grass (T,), leucaena (T2), napier grass-Ieucaena (T ,), napier grass-Ieucaena with starch added (50 g starch/kg fresh mixed forage) (T.) and napier grass-Ieucaena with formic acid added (2.3 ml per kg fresh mixed forage) (Ts)' Each of the treatment sample was stuffed into a two-litre laboratory silo (1.4-1.5 kg sample)and stored for 42 days. Samples were taken at the time of silo filling and after ensiling and analyzed for total nitrogen (T-N),volatile basic nitrogen (VBN) as per cent of total N, neutral detergent fibre (NDF), acid detergent fibre (ADF), cellulose, acid detergent lignin (ADL) and in vitro dry matter digestibility (IVDMD), Napier grass (T,) had significantly lower(P0.01) TNbut higher cell wall components except for ADL compared toTr The IVDMD of T 1was significantly higher(P0.05)than thatofT 2' Combination of napier grass with leucaena increased the T-N but reduced the fibres. Treatments T. andTs significantly differed (P0.05) inT-N, cell wall components and IVDMD fromeach other. Treatment T2 had asignificantly higher(P0.05)pHthan the others. Lactic acid was signficantly developed in T_. Only T, had some butyric acid. Treatment T. had the lowest VBN. NDF in all silages slightly decreased while ADF, cellulose and ADL in some cases slightly increased, IVDMD slightly decreased or remained unchanged on ensiling.
O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein ...interactions. However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer.
O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis.
Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells.
These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion.
Habitual aerobic exercise results in a significant increase in central arterial compliance. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and could play a role in ...mediating the habitual aerobic exercise-induced increase in central arterial compliance. The aim of the present study was to examine whether ET-1 is involved in the mechanisms underlying the increase in central arterial compliance with aerobic exercise training. Seven apparently healthy middle-aged and older (60 ± 3 years) adults underwent systemic endothelin-A/B (ETA/B)-receptor blockade (500 mg of Tracleer®) before and after 12 weeks of aerobic exercise training (70 ± 1% of maximal heart rate, 44 ± 2 min day⁻¹, 4.4 ± 0.1 days week⁻¹). Basal carotid arterial compliance (via simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) increased significantly after exercise training. Resting plasma ET-1 concentration decreased significantly after exercise training. Before exercise intervention, carotid arterial compliance increased significantly with the administration of the ETA/B-receptor blockade. After training, however, increases in carotid arterial compliance previously observed with the ETA/B-receptor blockade before training were abolished. Regular aerobic exercise training enhances central arterial compliance in middle-aged and older humans. The increase in arterial compliance was associated with the corresponding reduction in plasma ET-1 concentration as well as the elimination of ET-1-mediated vascular tone. These results suggest that reductions in ET-1 may be an important mechanism underlying the beneficial effect of exercise training on central artery compliance.
Are there empirical regularities in the shapes of letters and other human visual signs, and if so, what are the selection pressures underlying these regularities? To examine this, we determined a ...wide variety of topologically distinct contour configurations and examined the relative frequency of these configuration types across writing systems, Chinese writing, and nonlinguistic symbols. Our first result is that these three classes of human visual sign possess a similar signature in their configuration distribution, suggesting that there are underlying principles governing the shapes of human visual signs. Second, we provide evidence that the shapes of visual signs are selected to be easily seen at the expense of the motor system. Finally, we provide evidence to support an ecological hypothesis that visual signs have been culturally selected to match the kinds of conglomeration of contours found in natural scenes because that is what we have evolved to be good at visually processing.
We report that a macrocyclic ligand enables transfer of a protein from an aqueous phase to ionic liquids. The extraction behavior of heme protein cytochrome c (Cyt-c) from an aqueous phase into ionic ...liquids was investigated with crown ethers. A hydroxyl-group-containing ionic liquid with dicyclohexano-18-crown-6 was found to be capable of quantitative partitioning of Cyt-c, whereas the protein transfer using conventional organic solvents was negligibly small. Furthermore, we clarified that Cyt-c solubilized in ionic liquids caused a structural transformation of Cyt-c, which triggers its functional conversion from an electron-transfer protein to peroxidase.
Background Peripheral conduit artery endothelium-dependent dilatation decreases with aging in humans. Lactotripeptides (LTPs) and regular exercise can improve endothelium-dependent dilatation, but ...combining these lifestyle modifications may be more effective than either treatment alone. We conducted a randomized, place-controlled trial with four different intervention arms. Methods A total of 43 postmenopausal women (50–65 years old) were randomly divided into placebo, LTP, exercise and placebo (Ex+placebo), or exercise and LTP (Ex+LTP) groups. LTP or placebo was administered orally for 8 weeks. The exercise groups completed an 8-week moderate aerobic exercise (walking or cycling) intervention. Results There were no statistically significant differences in baseline flow-mediated dilatation (FMD) and most other key dependent variables among the groups. FMD significantly increased in the LTP, Ex+placebo, and Ex+LTP groups whereas no such changes were observed in the placebo control group. The magnitude of increases in FMD was significantly greater in the Ex+LTP group than other intervention groups. Conclusion We concluded that LTP ingestion combined with regular aerobic exercise improves endothelium-dependent dilatation to a greater extent than monotherapy with either intervention alone in postmenopausal women.
Human milk provides essential substrates for the optimal growth and development of a breastfed infant. Besides providing nutrients to the infant, human milk also contains metabolites which form an ...intricate system between maternal lifestyle, such as the mother's diet and the gut microbiome, and infant outcomes. This study investigates the variation of these human milk metabolites from five different countries. Human milk samples (
= 109) were collected one month postpartum from Australia, Japan, the USA, Norway, and South Africa and were analyzed by nuclear magnetic resonance. The partial least squares discriminant analysis (PLS-DA) showed separation between either maternal countries of origin or ethnicities. Variation between countries in concentration of metabolites, such as 2-oxoglutarate, creatine, and glutamine, in human milk, between countries, could provide insights into problems, such as mastitis and/or impaired functions of the mammary glands. Several important markers of milk production, such as lactose, betaine, creatine, glutamate, and glutamine, showed good correlation between each metabolite. This work highlights the importance of milk metabolites with respect to maternal lifestyle and the environment, and also provides the framework for future breastfeeding and microbiome studies in a global context.
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