Search

To verify the interaction between sodium polystyrene sulfonate (SPS) and its concomitant drugs, we elucidated the capability of potassium ions and concomitant drugs to adsorb onto SPS and the effect of their coexistence on the amount adsorbed. We identified 14 drugs used concomitantly with SPS from 2017-2019 in our investigation, and 5 drug preparations used in the clinical setting were used for the experiments. In the artificial intestinal juice, SPS adsorbed 39.05-69.77 mEq/g of potassium ions. Amlodipine besylate and nifedipine were well-adsorbed, while azosemide and febuxostat were did not adsorb well onto SPS. Our results and the results of a previous study suggest that additives in drug preparations affect the adsorption of drugs onto SPS. The adsorption kinetics onto SPS of drugs conformed to the pseudo-second order model. However, the adsorption of amlodipine besylate completely may not be fitted to the pseudo-second order model. The amount of amlodipine besylate adsorbed under the coexistence of potassium ions decreased compared to when potassium ions were absent. The amount of nifedipine and potassium ions adsorbed remained constant, regardless of whether potassium ions were present or not. These results might be due to the differences in their mechanisms of adsorption onto SPS and to the characteristics of the drugs. In a clinical setting, SPS is used concomitantly with various oral drugs. The interaction between SPS and its other concomitant drugs need to be elucidated more to obtain enough evidence for pharmacists to propose the appropriate prescription.

Oxidative stress is a major risk factor for Alzheimer’s disease (AD), which is characterized by brain atrophy, amyloid plaques, neurofibrillary tangles, and loss of neurons. 8-Oxoguanine, a major oxidatively generated nucleobase highly accumulated in the AD brain, is known to cause neurodegeneration. In mammalian cells, several enzymes play essential roles in minimizing the 8-oxoguanine accumulation in DNA. MUTYH with adenine DNA glycosylase activity excises adenine inserted opposite 8-oxoguanine in DNA. MUTYH is reported to actively contribute to the neurodegenerative process in Parkinson and Huntington diseases and some mouse models of neurodegenerative diseases by accelerating neuronal dysfunction and microgliosis under oxidative conditions; however, whether or not MUTYH is involved in AD pathogenesis remains unclear. In the present study, we examined the contribution of MUTYH to the AD pathogenesis. Using postmortem human brains, we showed that various types of MUTYH transcripts and proteins are expressed in most hippocampal neurons and glia in both non-AD and AD brains. We further introduced MUTYH deficiency into AppNL-G-F/NL-G-F knock-in AD model mice, which produce humanized toxic amyloid-β without the overexpression of APP protein, and investigated the effects of MUTYH deficiency on the behavior, pathology, gene expression, and neurogenesis. MUTYH deficiency improved memory impairment in AppNL-G-F/NL-G-F mice, accompanied by reduced microgliosis. Gene expression profiling strongly suggested that MUTYH is involved in the microglial response pathways under AD pathology and contributes to the phagocytic activity of disease-associated microglia. We also found that MUTYH deficiency ameliorates impaired neurogenesis in the hippocampus, thus improving memory impairment. In conclusion, we propose that MUTYH, which is expressed in the hippocampus of AD patients as well as non-AD subjects, actively contributes to memory impairment by inducing microgliosis with poor neurogenesis in the preclinical AD phase and that MUTYH is a novel therapeutic target for AD, as its deficiency is highly beneficial for ameliorating AD pathogenesis.

Background Plants are exposed to various forms of environmental stress. Penetration by pathogens is one of the most serious environmental insults. Wounding caused by tissue damage or herbivory also affects the growth and reproduction of plants. Moreover, wounding disrupts physical barriers present at the plant surface and increases the risk of pathogen invasion. Plants cope with environmental stress by inducing a variety of responses. These stress responses must be tightly controlled, because their unnecessary induction is detrimental to plant growth. In tobacco, WIPK and SIPK, two wound-responsive mitogen-activated protein kinases, have been shown to play important roles in regulating wound responses. However, their contribution to downstream wound responses such as gene expression is not well understood. Results To identify genes regulated by WIPK and SIPK, the transcriptome of wounded WIPK/SIPK-suppressed plants was analyzed. Among the genes down-regulated in WIPK/SIPK-suppressed plants, the largest group consisted of those involved in the production of antimicrobial phytoalexins. Almost all genes involved in the biosynthesis of capsidiol, a major phytoalexin in tobacco, were transcriptionally induced by wounding in WIPK/SIPK-dependent and -independent manners. 5-epi-aristolochene synthase (EAS) is the committing enzyme for capsidiol synthesis, and the promoter of EAS4, a member of the EAS family, was analyzed. Reporter gene analysis revealed that at least two regions each 40-50 bp length were involved in activation of the EAS4 promoter by wounding, as well as by artificial activation of WIPK and SIPK. Unlike transcripts of the capsidiol synthesis genes, accumulation of EAS protein and capsidiol itself were not induced by wounding; however, wounding significantly enhanced their subsequent induction by a pathogen-derived elicitor. Conclusions Our results suggest a so-called priming phenomenon since the induction of EAS by wounding is only visible at the transcript level. By inducing transcripts, not the proteins, of EAS and possibly other capsidiol synthesis genes at wound sites, plants can produce large quantities of capsidiol quickly if pathogens invade the wound site, whereas plants can minimize energy loss and avoid the cytotoxic effects of capsidiol where pathogens do not gain entry during wound healing., Article, BMC Plant Biology 19(1) : 576, (2019)

Este trabalho teve como objetivo avaliar o efeito do tempo de maturação sobre as características qualitativas da carne de bovinos Nelore. Foram colhidas 9 amostras do músculo Longissimus de 59 bovinos machos não-castrados, com idade média de 24 meses, 510 kg de peso vivo e confinados por um período médio de 95 dias. Cada amostra foi designada a um tempo de maturação totalizando nove períodos (0,3, 6, 9, 12, 15, 18, 21 e 28 dias) distintos, onde cada amostra foi identificada e embalada a vácuo individualmente e mantidas em câmara fria (0 - 2 ºC). Em cada período de maturação, as amostras foram retiradas da embalagem e foram expostas por 30 minutos em temperatura de 4°C a 6°C antes das avaliações objetivas da cor (L*, a* e b*) e pH. Em seguida, as amostras foram pesadas e assadas em temperatura controlada para a quantificação da perda por cocção e análise de força de cisalhamento. A força de cisalhamento reduziu 45% com 28 dias de maturação, sendo 12 dias considerado suficientes para que parte das amostras passassem de duras para macias. A perda por cocção teve um aumento de 3,8% com 28 dias de maturação, tendo crescimento acelerado até o 6º dia. A luminosidade teve crescimento até o 21ºdia, representando neste período um crescimento 8,6%, sendo o maior valor observado no 18º dia. Com relação à cores, o valor de vermelho e amarelo tiveram um rápido aumento até o 6º dia de maturação, tendo uma queda sutil e contínua até o 15º dia. A partir dos resultados obtidos, é possível concluir que a maciez da carne aumenta progressivamente com o tempo de maturação até 28 dias e a força de cisalhamento da carne avaliada 3 dias após o abate apresenta uma maior correlação com a força de cisalhamento avaliada em tempos subsequentes. This study aims to evaluate the effect of different maturation times on the qualitative traits of Nelore cattle. Nine samples of the Longissimus muscle were collected from 59 non-castrated male bovines, with a mean age of 24 months, 510 kg live weight and confined for an avarage period of 95 days. Each sample was designated at a maturation time totaling nine (0, 3, 6, 9, 12, 15, 18, 21 and 28 days) distinct periods, where each sample was individually vacuum packed and held in cold storage ( 0 - 2 ° C). At each maturation period, samples were removed from the package and exposed for 30 minutes at 4 ° C to 6 ° C before objective color evaluations (L *, a * and b *) and pH. Then, the samples were weighed and roasted in controlled temperature for the quantification of cooking loss and shear force analysis. The shear force reduced 45% with 28 days of aging, 12 days was considered sufficient for the samples to go from tough to tender. The cooking loss increased by 3.8% with 28 days of maturation, having accelerated growth until the 6th day. The luminosity increased until the 21st day, representing an 8.6% growth in this period, the highest value observed on the 18th day. Regarding colors, the red and yellow values had a rapid increase until the 6th day of aging, having a subtle and continuous drop until the 15th day. From the results obtained, it is possible to conclude that the meat tenderness increases progressively with the maturation time up to 28 days and the shear force of the meat evaluated 3 days after slaughter has a greater correlation with the shear force evaluated in subsequent times.

Plant cells enhance the tolerances to abiotic and biotic stresses via recognition of the stress, activation and nuclear import of signaling factors, up-regulation of defense genes, nuclear export of mRNA and translation of defense proteins. Nuclear pore-mediated transports should play critical roles in these processes, however, the regulatory mechanisms of nuclear-cytoplasmic transport during stress responses are largely unknown. In this study, a regulator of nuclear export of RNA and proteins, NbRanBP1-1 (Ran-binding protein1-1), was identified as an essential gene for the resistance of Nicotiana benthamiana to potato blight pathogen Phytophthora infestans. NbRanBP1-1-silenced plants showed delayed accumulation of capsidiol, a sesquiterpenoid phytoalexin, in response to elicitor treatment, and reduced resistance to P. infestans. Abnormal accumulation of mRNA was observed in NbRanBP1-1-silenced plants, indicating that NbRanBP1-1 is involved in the nuclear export of mRNA. In NbRanBP1-1-silenced plants, elicitor-induced expression of defense genes, NbEAS and NbWIPK, was not affected in the early stage of defense induction, but the accumulation of NbWIPK protein was reduced. Nuclear export of the small G-protein NbRan1a was activated during the induction of plant defense, whereas this process was compromised in NbRanBP1-1-silenced plants. Silencing of genes encoding the nuclear pore proteins, Nup75 and Nup160, also caused abnormal nuclear accumulation of mRNA, defects in the nuclear export of NbRan1a, and reduced production of capsidiol, resulting in decreased resistance to P. infestans. These results suggest that nuclear export of NbRan is a key event for defense induction in N. benthamiana, and both RanBP1-1 and nucleoporins play important roles in the process.

To understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. The sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. Sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. To avoid restraints, cables, and other stressful apparatuses and manipulations, telemetry systems have been developed. In the present study, sleep recordings in unrestrained cynomolgus monkeys (Macaca fascicularis) and common marmoset monkeys (Callithrix jacchus) were conducted to characterize normal sleep. For the analysis of sleep-wake rhythms in cynomolgus monkeys, telemetry electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG) signals were used. For the analysis of sleep-wake rhythms in marmosets, telemetry EEG and EOG signals were used. Both monkey species showed monophasic sleep patterns during the dark phase. Although non-rapid eye movement (NREM) deep sleep showed higher levels at the beginning of the dark phase in cynomolgus monkeys, NREM deep sleep rarely occurred during the dark phase in marmosets. Our results indicate that the use of telemetry in non-human primate models is useful for sleep studies, and that the different NREM deep sleep activities between cynomolgus monkeys and common marmoset monkeys are useful to examine sleep functions.

Objective To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1). Methods Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed. Results We identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region. Conclusions We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.

Nicotiana benthamiana ABCG1 and ABCG2 are ABC transporters which are probably involved in the export of capsidiol, the major phytoalexin of Nicotiana species. While capsidiol export by these transporters plays an essential role in post-invasion defense against Phytophthora infestans, they also export unidentified antimicrobial compound(s) involved in pre-invasion defense. In this study, promoter activity of NbABCG2 (Pabcg2a) was analyzed using a GFP marker. Expression of GFP under the control of Pabcg2a was significantly increased by co-expression with the INF1 elicitor from P. infestans. Disruption of the ethylene-responsive GCC box in Pabcg2a compromised INF1-induced activation of Pabcg2a. Consistently, penetration by P. infestans was increased by gene-silencing of NbEIN2, the key ethylene-signaling component, suggesting the involvement of ethylene for pre-invasion defense of N. benthamiana.

The complete genome sequence of the endophytic diazotroph Kosakonia sacchari , isolated from a sweet potato, was analyzed. The 4,902,106-bp genome with 53.7% G+C content comprises 4,638 open reading frames, including nif genes, 84 tRNAs, and seven complete rRNAs in a circular chromosome.

A healthy 60-year-old female presented with acute-onset low back pain, fever, reduced consciousness, and meningeal irritation. Gram-positive cocci were observed in the cerebrospinal fluid, and methicillin-susceptible Staphylococcus aureus was cultured from blood and cerebrospinal fluid. Spinal magnetic resonance imaging demonstrated osteomyelitis around L5 (Fig. A). This article is protected by copyright. All rights reserved.

A glycosidically bound fraction was prepared by adsorbing a 80% methanol extract from fresh rhizomes of ginger onto a column of Amberlite XAD-2 resin and successively eluting with ethyl acetate or methanol. Enzymatic hydrolysis of this fraction with an acetone powder prepared from fresh ginger and commercial glycosidase liberated such alcohols as geraniol, 2-heptanol, α-terpineol, nerol, linalool, and citronellol, suggesting that fresh ginger included glycosides and glycosidase. The ethyl acetate eluate was chromatographed by an ODS flash column and then HPLC to isolate the β-glucopyranosides of 5-hydroxyborneol, 1,8-epoxy-p-menthan-3-ol, (2E, 6E)- and (2E, 6Z)-3,7-dimethyl-8-hydroxyoctadien-1-ol, 2-heptanol, geraniol, nerol, (R)-linalool, and citronellol. All the glucosides, except for 5-hydroxybornyl-O-β-D-glucopyranoside, were identified for the first time in the rhizome of ginger, and many of their aglycons were major constituents of the essential oil. The results indicate that these glucosides are aroma precursors of fresh ginger.

Interactions between micelles and tripositive ions of metal complexes such as [M(en)3]3+ (M = Co or Cr, en = ethylenediamine), [M(chxn)3]3+ (chxn = (R,R)-1,2-cyclohexanediamine), and [M(phen)3]3+ (phen = 1,10-phenanthroline), were studied using 59Co NMR spectroscopies and paramagnetic Cr(III)-induced 13C NMR relaxations of the surfactants. The magnitudes of the changes in 59Co chemical shifts and relaxation rates for [Co(en)3]3+ (= en complex) and [Co(chxn)3]3+ (= chxn complex) were dependent on the type of the head group: The carboxylate and alaninate surfactants caused larger changes in the 59Co NMR parameters than the sulfonate and sulfate ones did. The 59Co longitudinal and transverse relaxation rates were measured for the typical systems; these results gave effective 59Co electric field gradients (efgs) and effective correlation times for the three complex ions in the micellar solutions. The effective 59Co efgs obtained for the en and chxn complexes were larger in the carboxylate micelles than in th...

59Co NMR relaxation rates for the [Co(chxn)3]3+ (chxn = trans-(1R,2R)-1,2-diaminocyclohexane) and [Co(en)3]3+ (en = ethylenediamine) ions were measured in the presence of sulfate or oxalate ions. 1H relaxation rates for the chxn ligands in the same systems were also measured. The ratios of the 59Co relaxation rates to the 1H ones indicate that the 59Co electric field gradient of [Co(chxn)3]3+ is appreciably decreased by the formation of the 1:1 ion pair with the sulfate ion. The difference of the concentration dependence of the 59Co NMR relaxations between the sulfate and the oxalate ions can be attributed to the faster change in the configuration of the 1:1 ion pair of the oxalate ion.

Bovine mammary epithelial cells (BMEC) were isolated as acinous fragments from a mammary gland of a lactating cow. They grew well on plastic substratum, showed the characteristic cobblestone morphology of epithelial cells, and secreted alpha s1-, beta-, and kappa-caseins even when grown on plastic substratum. A plasmid containing the bacterial chloramphenicol acetyl transferase (CAT) gene was transfected to the isolated BMEC by calcium phosphate precipitation and electroporation methods. The transfection efficiency of BMEC by the calcium phosphate method was greatly improved by post-transfection osmotic shock with glycerol or polyethylene glycol. An about 700 bp DNA fragment containing 5'-flanking sequence of bovine alpha s1-casein gene showed promoter activity in the transfected BMEC. The primary culture of BMEC might be useful for studies on regulation of bovine milk-protein gene expression.