Carotenoids exert beneficial effects on human health through their excellent antioxidant activity. To increase carotenoid productivity in the marine Pennales Phaeodactylum tricornutum, we genetically ...engineered the phytoene synthase gene (psy) to improve expression because RNA-sequencing analysis has suggested that the expression level of psy is lower than other enzyme-encoding genes that are involved in the carotenoid biosynthetic pathway. We isolated psy from P. tricornutum, and this gene was fused with the enhanced green fluorescent protein gene to detect psy expression. After transformation using the microparticle bombardment technique, we obtained several P. tricornutum transformants and confirmed psy expression in their plastids. We investigated the amounts of PSY mRNA and carotenoids, such as fucoxanthin and β-carotene, at different growth phases. The introduction of psy increased the fucoxanthin content of a transformants by approximately 1.45-fold relative to the levels in the wild-type diatom. However, some transformants failed to show a significant increase in the carotenoid content relative to that of the wild-type diatom. We also found that the amount of PSY mRNA at log phase might contribute to the increase in carotenoids in the transformants at stationary phase.
Spontaneous breathing potentially injures lungs and diaphragm when spontaneous effort is vigorous in acute respiratory distress syndrome (ARDS) while immobility also has risks of Intensive Care Unit ...(ICU) acquired weakness and diaphragm atrophy. Thus, ventilatory strategy to mitigate strong spontaneous effort should be promptly established without a systemic use of neuromuscular blocking agent. Here, we investigated the impacts of positive end-expiratory pressure (PEEP) and body position on the capacity of force generation from diaphragm following bilateral phrenic nerve stimulations in a rabbit ARDS model.
Using lung-injured rabbits, we measured 1) transdiaphragmatic pressure by bilateral phrenic nerve stimulation and 2) end-expiratory lung volume using computed tomography, under two different levels of PEEP (high, low) and body positions (supine, prone).
Overall, transdiaphragmatic pressure was the highest at low PEEP in supine position and the lowest at high PEEP in prone position. Compared to values in low PEEP + supine, transdiaphragmatic pressure was significantly reduced by either prone alone (the same PEEP) or increasing PEEP alone (the same position) or both combinations. End-expiratory lung volume was significantly increased with increasing PEEP in both positions, but it was not altered by body position.
The capacity of force generation from diaphragm was modulated by PEEP and body position during mechanical ventilation in ARDS. Higher PEEP or prone position per se or both was effective to decrease the force generation from diaphragm.
Herein, we describe a highly potent gravitropic bending inhibitor with no concomitant growth inhibition. Previously, we reported that (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) selectively ...inhibits root gravitropic bending of lettuce radicles at 5 μM. Based on the structure-activity relationship study of ku-76 as a lead compound, we designed and synthesized various C4-substituted analogs of ku-76. Among the analogs, 4-phenylethynyl analog exhibited the highest potency for gravitropic bending inhibition, which was effective at only 0.01 μM. Remarkably, 4-phenylethynyl analog is much more potent than the known inhibitor, NPA. Substitution in the para position on the aromatic ring of 4-phenylethynyl group was tolerated without diminished activity. In addition, evaluation using Arabidopsis indicated that 4-phenylethynyl analog inhibits gravitropism by affecting auxin distribution in the root tips. Based on the effects on Arabidopsis phenotypes, 4-phenylethynyl analog may be a novel inhibitor that differs in action from the previously reported auxin transport inhibitors.
Grain-filling ability is one of the factors that controls grain yield in rice (Oryza sativa L.). We developed a method for describing grain weight distribution, which is the probability density ...function of single grain weight in a panicle, using 128 Japanese rice varieties. With this method, we quantitively analyzed genotypic differences in grain-filling ability and used the grain weight distribution parameters for genomic prediction subject to genetic improvement in grain yield in rice. The novel description method could represent the observed grain weight distribution with five genotype-specific parameters of a mixture of two gamma distributions. The estimated genotype-specific parameters representing the proportion of filled grains had applicability to explain the grain filling ability of genotypes comparable to that of sink-filling rate and the conventionally measured proportion of filled grains, which suggested the efficiency and flexibility of grain weight distribution parameters to handle several genotypes. We revealed that perfectly filled grains have to be prioritized over partially filled grains for the optimum allocation of the source of yield in a panicle, from the analysis for obtaining an ideal shape of grain weight distribution. We conducted genomic prediction of grain weight distribution considering five genotype-specific parameters of the distribution as phenotypes relating to grain filling ability. The proportion of filled grains, average weight of filled grains, and variance of filled grain weight, which were considered to control grain yield to a certain degree, were predicted with accuracies of 0.30, 0.28, and 0.53, respectively. The proposed description method of grain weight distribution facilitated not only the investigation of the optimum allocation of nutrients in a panicle for realizing high grain-filling ability, but also allowed genomic selection of grain weight distribution.
Although several studies have investigated the possible association between elevated vitamin D and calcium intake and low breast cancer risk, findings have been inconsistent. We conducted a ...case‐control study to clarify the association between vitamin D and calcium intake and breast cancer risk among pre‐ and post‐ menopausal women in Japan. We also investigated whether these effects were modified by tumor receptor status, specifically estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor‐2 (HER2) status. We examined 1803 breast cancer patients and 3606 age‐ and menopausal status‐matched noncancer controls. Among cases, 713 were assessed for ER, PR, and HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional or unconditional logistic models adjusted for potential confounders. A significant inverse association was observed between vitamin D and calcium intake and breast cancer risk among all subjects, with top quartile ORs of 0.76 (95% CI, 0.63–0.90; trend P = 0.001) and 0.83 (95% CI, 0.69–0.99; trend P = 0.038), respectively. In analyses stratified by menopausal status, a significant association between risk and vitamin D was observed only among premenopausal women (trend P < 0.001), whereas that between risk and calcium intake was seen only among postmenopausal women (trend P = 0.022). Heterogeneity by menopausal status for these associations was statistically significant. This association was modified by tumor receptor status. These findings suggest that the protective effects of vitamin D and calcium intake against breast cancer risk may differ by menopausal status and receptor status.
(Cancer Sci 2010; 101: 1234–1240)
Genomic selection (GS) can be a powerful technology in conifer breeding because conifers have long generation intervals, protracted evaluation times, and high costs of breeding inputs. To elucidate ...the potential of GS for conifer breeding, we simulated 60-year breeding programs in
Cryptomeria japonica
with and without GS. In conifers, the rapid decay of linkage disequilibrium (LD) can constitute a severe barrier to application of GS. For overcoming that barrier, we proposed an idea to leverage a seed orchard system, which has been used commonly in conifers, because some degree of LD exists in progenies derived from the limited number of elite trees in a seed orchard. The base population used for simulations consisted of progenies from 25 elite trees. Results show that GS breeding (GSB) done without model updating outperformed phenotypic selection breeding (PSB) during the first 30 years, but the genetic gain achieved over the 60 years was smaller in GSB than in PSB. However, GSB with model updating outperformed PSB over the 60 years. The genetic gain achieved over the 60 years of GSB with model updating was nearly twice that of PSB. Advantages of GSB over PSB prevailed, even for a low heritability polygenic trait. The number of markers necessary for efficient GS was a realistic level (e.g., one in every 1 cM), although higher marker density engendered higher accuracy of selection. These results suggest that GS can be useful in
C
.
japonica
breeding. Updating of the prediction model was, however, indispensable for attaining the large genetic gain.
Objective
The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) ...reflects quantitative amyloid measurements and the time course of
11
C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer’s disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time.
Methods
From the National Bioscience Database Center Human Database of the Japanese Alzheimer’s Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer’s disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β
1-42
(CSF-Ab
42
) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab
42
were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive).
Results
From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (
F
= 174.9,
p
< 0.001). The baseline CSF-Ab
42
level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (
F
= 37,
p
< 0.001). Over the 3-year follow-up, annual changes in SUVR were − 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (
F
= 8.4,
p
< 0.001).
Conclusions
Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.
The anthocyanin composition and antioxidant activity of the crowberry (Empetrum nigrum) were studied. High-performance liquid chromatography (HPLC) combined with a diode array detector and ...electrospray ionization mass spectrometry were used for identification and quantification of individual anthocyanins. Freeze-dried crowberry powder was extracted with 80% methanol containing 0.5% acetic acid and subjected to HPLC. Thirteen kinds of anthocyanins were identified. The major anthocyanins were cyanidin-3-galactoside and delphinidin-3-galactoside, at 8.04 and 8.62 mg/g extract, respectively. The HPLC profile of crowberry extract was similar to bilberry and blueberry. The total content of anthocyanins in crowberry was 41.8 mg/g extract, higher than the other nine major berry species (2.5−38.8 mg/g extract). The antioxidant activity was also evaluated using the 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis(3-ethybenzothiazoline-6-sulfonic acid) radical quenching assays and the ferric reducing activity power assy. Crowberry extract exerted the strongest antioxidant activity. In conclusion, individual anthocyanins in crowberry were identified and then quantified in this study. Additionally, crowberry is suggested to be associated with a reduction in the risk of developing chronic diseases because of its strong antioxidant activity.
Purpose
Lithium is a nutritionally essential trace element predominantly contained in vegetables, plant-derived foods, and drinking water. Environmental lithium exposure and concurrent nutritional ...intake vary considerably in different regions. We here have analyzed the possibility that low-dose lithium exposure may affect mortality in both metazoans and mammals.
Methods
Based on a large Japanese observational cohort, we have used weighted regression analysis to identify putative effects of tap water-derived lithium uptake on overall mortality. Independently, we have exposed
Caenorhabditis elegans
, a small roundworm commonly used for anti-aging studies, to comparable concentrations of lithium, and have quantified mortality during this intervention.
Results
In humans, we find here an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals (β = −0.661,
p
= 0.003). Consistently, we find that exposure to a comparably low concentration of lithium chloride extends life span of
C. elegans
(
p
= 0.047).
Conclusions
Taken together, these findings indicate that long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species.
The self-assembled bilayer lipid membrane (BLM) is the basic component of the cell membrane. The reconstitution of ion channel proteins in artificially formed BLMs represents a well-defined system ...for the functional analysis of ion channels and screening the effects of drugs that act on them. However, because BLMs are unstable, this limits the experimental throughput of BLM reconstitution systems. Here we report on the formation of mechanically stable solvent-free BLMs in microfabricated apertures with defined nano- and micro-tapered edge structures. The role of such nano- and micro-tapered structures on the stability of the BLMs was also investigated. Finally, this BLM system was combined with a cell-free synthesized human ether-a-go-go-related gene channel, a cardiac potassium channel whose relation to arrhythmic side effects following drug treatment is well recognized. Such stable BLMs as these, when combined with a cell-free system, represent a potential platform for screening the effects of drugs that act on various ion-channel genotypes.