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Many effluents contain various antibiotics commonly, where the simultaneous removal of them is a big challenge. In this study, the magnetic biocomposite (eggshell-zeolitic imidazolate framework) was designed and synthesized by green and facile method. Zeolitic imidazolate framework-8 (ZIF-8) particles were stabilized on the surface of magnetic eggshell (Fe 3 O 4 -ES), generating a new Fe 3 O 4 -ES/ZIF-8 adsorbent, which was also fully characterized using FTIR, XRD, SEM and BET techniques. Thereafter, norfloxacin (NOR) adsorption processes were investigated through different influencing factors (dosage, concentration, pH and temperature). The Langmuir adsorption isotherm could confirm a maximum removal efficiency of 80.13% for NOR. Kinetic studies illustrated that the pseudo-first-order model was in line with the experimental data of the simultaneous removal of NOR. Moreover, the magnetic nature of the adsorbent caused an easy separation from the aqueous solution.

The blood-brain barrier (BBB) controls the entry of chemicals from the blood to the brain. Since brain drugs need to penetrate the BBB, rapid and reliable prediction of BBB penetration (BBBP) is helpful for drug development. In this study, free-form and in-blood-form datasets were prepared by modifying the original BBBP dataset, and the effects of the data modification were investigated. For each dataset, molecular descriptors were generated and used for BBBP prediction by machine learning (ML). For ML, the dataset was split into training, validation, and test data by the scaffold split algorithm MoleculeNet used. This creates an unbalanced split and makes the prediction difficult; however, we decided to use that algorithm to evaluate the predictive performance for unknown compounds dissimilar to existing ones. The highest prediction score was obtained by the random forest model using 212 descriptors from the free-form dataset, and this score was higher than the existing best score using the same split algorithm without using any external database. Furthermore, using a deep neural network, a comparable result was obtained with only 11 descriptors from the free-form dataset, and the resulting descriptors suggested the importance of recognizing the glucose-like characteristics in BBBP prediction.

The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that increases the transcription of multiple genes. ChREBP is highly localized in the liver, where it upregulates the expression of genes that code for glycolytic and lipogenic enzymes, resulting in the conversion of excess carbohydrate into storage fat. ChREBP knockout (KO) mice display an anti-obese phenotype. However, at this time, role of ChREBP in adipose tissue remains unclear. Therefore, the energy metabolism and morphology of mitochondrial brown adipose tissue (BAT) in ChREBP KO mice was examined. We found increased expression levels of electron transport system proteins including the mitochondrial uncoupling protein (UCP1), and mitochondrial structural alterations such as dysplasia of the cristae and the presence of small mitochondria in BAT of ChREBP KO mice. Mass spectrometry analyses revealed that fatty acid synthase was absent in the BAT of ChREBP KO mice, which probably led to a reduction in fatty acids and cardiolipin, a regulator of various mitochondrial events. Our study clarified the new role of ChREBP in adipose tissue and its involvement in mitochondrial function. A clearer understanding of ChREBP in mitochondria could pave the way for improvements in obesity management., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The carbohydrate response element-binding protein (ChREBP), a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis, exists as two isoforms: ChREBPα and ChREBPβ. However, the mechanism responsible for regulating the expression of both ChREBPα and β, as well as the mechanism that determines which specific isoform is more responsive to different stimuli, remains unclear. To address this issue, we compared the effects of several stimuli, including oxidative stress, on the mRNA and protein expression levels of ChREBPα and β in the hepatocyte cell line, HepG2. We found that H 2 O 2 stimulation suppressed the expression of both mRNA and protein in HepG2 cells, but the mRNA expression level of ChREBPβ was < 1% of that for ChREBPα levels. In addition, the reduction in both ChREBPα and β mRNA levels was reversed by PD98059, a selective and cell permeable inhibitor of the MEK/ERK pathway. Additionally, the administration of 12-O-tetradecanoylphorbol 13-acetate (TPA) and staurosporine (STS), activators of extracellular-signal-regulated kinase (ERK) signaling, also resulted in a decrease in the levels of both ChREBPα and β mRNA in HepG2 cells through ERK signaling. These collective data suggest that oxidative stress, including STS treatment, suppresses the expression of ChREBPα and β via the activation of ERK signaling in HepG2 cells. Such a decrease in the levels of expression of ChREBPα and β could result in the suppression of hepatic glycolysis and lipogenesis, and this would be expected to prevent further oxidative stress., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic., Methods: This retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016-2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends., Results: In all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities., Conclusions: The COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Team-based learning (TBL) is an active learning method used in many educational institutions. However, there are few examples of its use in basic medicine, such as biochemistry in medical schools. This study used TBL to teach glucose metabolism to first-year medical students. The process was in four phases: preclass preparation, readiness assurance tests, advanced questions, and a TBL test, with peer evaluation and a questionnaire. There were positive correlations between the TBL test, peer evaluation, and individual readiness test performance. Tests were taken immediately after learning and 2 weeks later, and scores decreased significantly less with TBL than traditional lectures (-2.3% vs. -17.5%). This suggests that TBL was more effective than traditional lectures in supporting knowledge retention. We used a Moodle system to facilitate communication between students and teachers, and this was evaluated positively by both groups. It was particularly useful for managing TBL. These findings suggest that TBL could be used to improve student performance in biochemistry., (© 2020 International Union of Biochemistry and Molecular Biology.)

Oxido bridges commonly form between iron(III) ions, but their bond angles and symmetry vary with the circumstances. A large number of oxido-bridged dinuclear iron(III) complexes have been structurally characterized. Some of them belong to the C 2 point group, possessing bent Fe-O-Fe bonds, while some others belong to the C i symmetry, possessing the linear Fe-O-Fe bonds. The question in this study is what determines the structures and symmetry of oxido-bridged dinuclear iron(III) complexes. In order to gain further insights, three oxido-bridged dinuclear iron(III) complexes were newly prepared with 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) ligands: [Fe 2 OCl 2 (bpy) 4 ][PF 6 ] 2 ( 1 ), [Fe 2 O(NO 3 ) 2 (bpy) 4 ][PF 6 ] 2 ·0.6MeCN·0.2(2-PrOH) ( 2 ), and [Fe 2 OCl 2 (phen) 4 ][PF 6 ] 2 ·MeCN·0.5H 2 O ( 3 ). The crystal structures of 1 , 2 , and 3 were determined by the single-crystal X-ray diffraction method, and all of them were found to have the bent Fe-O-Fe bonds. Judging from the crystal structure, some intramolecular interligand hydrogen bonds were found to play an important role in fixing the structures. Additional density functional theory (DFT) calculations were conducted, also for a related oxido-bridged dinuclear iron(III) complex with a linear Fe-O-Fe bond. We conclude that the Fe-O-Fe bridge tends to bend like a water molecule, but is often stretched by interligand steric repulsion, and that the structures are mainly controlled by the intramolecular interligand interactions.

Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the effect of GJG on the activation of resident glial cells and on p38-TNF signaling in two mouse models of neurological disorders: the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. GJG administration relieved the severity of clinical EAE symptoms and MPTP-induced inflammation by decreasing the number of microglia and the production of TNF-α in the spinal cord of EAE mice and the substantia nigra of MPTP-treated mice. Accordingly, GJG suppressed the phosphorylation of p38 in glial cells of these two mouse models. We conclude that GJG attenuates inflammation of the CNS by suppressing glial cell activation, followed by a decrease in the production of TNF-α via p38-TNF signaling.

The correlation between magnetic relaxation dynamics and the alignment of single-ion magnets (SIMs) in a crystal was investigated using four analogous cobalt(ii) complexes with unique hydrogen-bond networks. The hydrogen-bonding interactions in the crystals resulted in a relatively short intermolecular Co⋯Co distance, which led to non-zero intermolecular magnetic coupling. All the complexes with a Co⋯Co distance shorter than 6.5 Å exhibited zero-field slow magnetic relaxation as weak magnetic interactions split the ground ±M s levels and suppressed quantum tunneling of magnetization (QTM). In particular, antiferromagnetically coupled one-dimensional chain SIM networks effectively suppressed QTM when the two intrachain Co⋯Co distances were non-equivalent. However, when the two distances in a chain were equivalent and each molecular symmetry axis aligned parallell within the chain, QTM suppression was insufficient because magnetic coupling from the adjacent molecules was virtually cancelled. Partial substitution of the Co II ion with the diamagnetic Zn II ion up to 33% for this complex resulted in complete QTM suppression in the absence of an external field. These results show that the manipulation of intermolecular distances and alignments is effective for suppressing undesired QTM events in SIMs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. In response to fluctuating blood glucose levels ChREBP activity is regulated mainly by nucleocytoplasmic shuttling of ChREBP. Under high glucose ChREBP binds to importin α and importin β and translocates into the nucleus to initiate transcription. We have previously shown that the nuclear localization signal site (NLS) for ChREBP is bipartite with the NLS extending from Arg158 to Lys190. Here, we report the 2.5 Å crystal structure of the ChREBP-NLS peptide bound to importin α. The structure revealed that the NLS binding is monopartite, with the amino acid residues K171RRI174 from the ChREBP-NLS interacting with ARM2-ARM5 on importin α. We discovered that importin α also binds to the primary binding site of the 14-3-3 proteins with high affinity, which suggests that both importin α and 14-3-3 are each competing with the other for this broad-binding region (residues 117-196) on ChREBP. We screened a small compound library and identified two novel compounds that inhibit the ChREBP-NLS/importin α interaction, nuclear localization, and transcription activities of ChREBP. These candidate molecules support developing inhibitors of ChREBP that may be useful in treatment of obesity and the associated diseases., (© 2020 The Author(s).)

Objective: To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease., Methods: We searched for ADSSL1 variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants., Results: We identified 63 patients from 59 families with biallelic variants of ADSSL1 . Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed that ADSSL1 myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center., Conclusions: ADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features., (© 2020 American Academy of Neurology.)

Pentakis(dimethylsulfoxide-κ O )oxidovanadium(iv) bis(tetraphenylborate), [VO(dmso) 5 ][BPh 4 ] 2 (dmso: dimethylsulfoxide), was synthesized, and its pseudo- C 4 VO 6 coordination geometry was revealed by a single-crystal X-ray method. A novel equation set was obtained for magnetic susceptibility and magnetization of the d 1 complexes, considering the axial distortion and the spin-orbit coupling for the 2 D free-ion term. The equation set enabled magnetic simulation for significantly symmetry-lowered d 1 complexes to obtain the anisotropic g -values and also the excitation energies. In addition, conformational prediction was conducted, using the enumeration results on the basis of the group theory. The dominant conformers were predicted on the basis of the density functional theory (DFT) method, and especially, the conformer in the crystal was successfully predicted by a deep neural network method., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The reactions of [Ru 2 (O 2 CCH 3 ) 4 Cl] with 2-aminopyridine (Hamp) and 2-amino-4-methylpyridine (Hammp) afforded two novel Ru 2 complexes, [Ru 2 (amp) 4 Cl 2 ] (1) and [Ru 2 (ammp) 4 Cl 2 ] (2), respectively. Single crystal X-ray diffraction analyses revealed that 1 and 2 adopted typical paddlewheel-type structures, where the Ru 2 units are coordinated with four aminopyridinate ligands with a cis-2:2 arrangement at the equatorial positions and two chloride ligands at the axial positions. The stabilities of 1 and 2 were supported by unrestricted density functional theory (uDFT) calculations. The zero-point energies of the three structural isomers (trans-2:2, 3:1, and 4:0 arrangements) of 1 and 2 were less stable than those of the respective cis-2:2 arrangements. Temperature-dependences of the magnetic susceptibility measurements and uDFT calculations showed that the oxidation and spin states of the Ru 2 units in 1 and 2 were commonly Ru 2 6+ and triplet states, respectively. Cyclic voltammetry showed that 1 and 2 underwent one-electron reduction processes, i.e., 1/1 - and 2/2 - , at redox potentials (E 1/2 ) of -0.08 and -0.18 V vs. SCE, respectively. These results agreed well with the DFT-calculated E 1/2 values of 1 (-0.08 V vs. SCE) and 2 (-0.18 V vs. SCE) and were theoretically attributed to Ru 2 -centred (δ*(Ru 2 )) redoxes. Moreover, 1 and 2 showed unique near-infrared absorption bands at approximately 1200-1500 nm, which were theoretically attributed to the ligand-to-metal charge transfer (LMCT) with π(amp or ammp) →δ*(Ru 2 ) transition characteristics.

Strains of Rotarix, a live attenuated monovalent oral rotavirus vaccine, replicate in the intestine and are shed for about one month in immunocompetent recipients. The current study aimed to identify genetic changes of shed strains to reveal any significant mutations and their clinical impact on recipients. Stool samples of recipients of the first dose of Rotarix were sequentially collected for one month from the day of administration. Sequence analyses of the VP7 gene in eight recipients revealed five amino acid substitutions. Among them, two were observed in aa123, which is located in antigenic region 7-1a. Since there were no associated clinical symptoms, the genetic changes were unlikely to have caused reversion of pathogenicity of vaccine strain. Of interest, the virus in one case became closer to wild-type rotavirus via an amino acid change at aa123 occurring 14 days after administration, which might have resulted from multiple replications and long-term shedding of the vaccine strain., Competing Interests: The authors declare that there are no conflicts of interest., (© 2019 The Authors.)

The crystal structure of a new magnesium(ii) complex, [Mg(dmso) 6 ][BPh 4 ] 2 (1) (dmso: dimethylsulfoxide), was determined, and the reason for the observed structure was clarified by conformational analysis. For a dmso-ligand arm, three conformations, α, β, and γ, are possible. The α-arm is the most energetically favourable and is suitable for reducing the steric repulsion between the arms; the β-arm is less energetically favourable, but can be stabilized by interaction with surroundings (e.g. CHπ interaction); the γ-arm is not energetically favourable, but is effective in reducing the size of the complex cation. From the conformational analysis, the most stable conformer of the [Mg(dmso) 6 ] 2+ complex cation was found to be the α 6 conformer, and the complex cation in dmso solution was predicted to exist as a mixture of α 6 , α 5 β, and trans-α 4 β 2 species. On the contrary, in the crystal structure, the trans-β 2 γ 4 species, considered to be unstable, was observed. From the conformational analysis in the tetraphenylborate surroundings, the trans-β 2 γ 4 structure was found to become more stable, due to its small size suitable for crystal packing with bulky tetraphenylborate anions.

University lectures are mainly passive in nature, and there are few subjects in which students need to learn and function independently. Tutorial education and related activities at universities that specialize in medical and pharmaceutical training have been actively carried out, and lectures in conjunction with practical skills are gradually being developed, although progress has been slow in this area. In past years, our biochemistry practice classes have been evaluated in reports dealing with experiments and written examinations, as is done in other universities. However, using this methodology, we are not able to evaluate the extent to which students master biochemical experimental skills. To address this, we introduced a basic skill test to our biochemical curriculum for the first time. Our exams contributed to a deeper understanding of student skills and could be good tools for evaluating the degree of understanding of the students. The students understood the contents of the training well and felt interested in research in the field of basic medicine. Thus, we conclude that introducing practical testing to biochemical practice was effective for medical students in the field of biochemistry. © 2019 International Union of Biochemistry and Molecular Biology, 47(3):279-287, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

We report a biomimetic polyelectrolyte based on amphiphilic polymer nanosheet multilayer films. Copolymers of poly( N-dodecylacrylamide- co-vinylphosphonic acid) [p(DDA/VPA)] form a uniform monolayer at the air-water interface. By depositing such monolayers onto solid substrates using the Langmuir-Blodgett (LB) method, multilayer lamellae films with a structure similar to a bilayer membrane were fabricated. The proton conductivity at the hydrophilic interlayer of the lamellar multilayer films was studied by impedance spectroscopy under temperature- and humidity-controlled conditions. At 60 °C and 98% relative humidity (RH), the conductivity increased with increasing mole fraction of VPA ( n) up to 3.2 × 10 -2 S cm -1 for n = 0.41. For a film with n = 0.45, the conductivity decreased to 2.2 × 10 -2 S cm -1 despite the increase of proton sources. The reason for this decrease was evaluated by studying the effect of the distance between the VPAs ( l VPA ) on the proton conductivity as well as their activation energy. We propose that for n = 0.41, l VPA is the optimal distance not only to form an efficient two-dimensional (2D) hydrogen bonding network but also to reorient water and VPA. For n = 0.45, on the other hand, the l VPA was too close for a reorientation. Therefore, we concluded that there should be an optimal distance to obtain high proton conductivity at the hydrophilic interlayer of such multilayer films.

Caffeine intake is associated with a reduced risk developing non-alcoholic fatty liver disease (NAFLD), but the underlying molecular mechanisms remain to be fully elucidated. We report here that caffeine markedly improved high fat diet-induced NAFLD in mice resulting in a 10-fold increase in circulating IL-6 levels, leading to STAT3 activation in the liver. Interestingly, the expression of IL-6 mRNA was not increased in the liver, but increased substantially in the muscles of caffeine-treated mice. Caffeine was found to stimulate IL-6 production in cultured myotubes but not in hepatocytes, adipocytes, or macrophages. The inhibition of p38/MAPK abrogated caffeine-induced IL-6 production in muscle cells. Caffeine failed to improve NAFLD in IL-6 and hepatocyte-specific STAT3 knockout mice, indicating that the IL-6/STAT3 pathway is vital for the hepatoprotective effects of caffeine in NAFLD. The possibility that IL-6/STAT3-mediated hepatic autophagosome induction and hepatocytic oxygen consumption are involved in the anti-NAFLD effects of caffeine cannot be excluded, based on the findings presented here. Our results reveal that caffeine ameliorates NAFLD via crosstalk between muscle IL-6 production and liver STAT3 activation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three tetracoordinated cobalt(ii) complexes with a series of unsymmetrical bidentate ligands were synthesized and crystallographically characterized. Although their static magnetic properties are similar, their dynamic magnetic properties differ drastically depending indirectly on intermolecular hydrogen-bonding interactions.

Under certain conditions, amyloid-like fibrils can develop into three-dimensional networks and form hydrogels by a self-assembly process. When Cu/Zn superoxide dismutase (SOD1), an anti-oxidative enzyme, undergoes misfolding, fibrillar aggregates are formed, which are a hallmark of a certain form of familial amyotrophic lateral sclerosis (ALS). However, the issue of whether SOD1 fibrils can be assembled into hydrogels remains to be tested. Here, we show that the SOD1 polypeptides undergo hydrogelation accompanied by the formation of thioflavin T-positive fibrils at pH 3.0 and 4.0, but not at pH 5.0 where precipitates are formed. The results of viscoelastic analyses indicate that the properties of SOD1 hydrogels (2%) were similar to and slightly more fragile than a 0.25% agarose gel. In addition, monitoring by a quartz crystal microbalance with admittance analysis showed that the denaturing of immobilized SOD1 on a sensor under the hydrogelation conditions at pH 3.0 and 4.0 resulted in an increase in the effective acoustic thickness from ~3.3 nm (a folded rigid form) to ~50 and ~100 nm (an extended water-rich state), respectively. In contrast, when SOD1 was denatured under the same conditions at pH 5.0, a compact water-poor state with an effective acoustic thickness of ~10 nm was formed. The addition of physiological concentrations of NaCl to the pH 4.0 sample induced a further extension of the SOD1 with larger amounts of water molecules (with an effective acoustic thickness of ~200 nm) but suppressed hydrogel formation. These results suggest that different denatured intermediate states of the protein before self-assembly play a major role in determining the characteristics of the resulting aggregates and that a conformational change to a suitable level of extended water-rich intermediate state before and/or during intermolecular assembling is required for fibrillation and hydrogelation in the case of globular proteins., Competing Interests: The authors have declared that no competing interests exist.

The magnetostructural correlation of the hexakis-dmso cobalt(ii) complex, [Co(dmso) 6 ](BPh 4 ) 2 (dmso: dimethylsulfoxide), was investigated by single-crystal X-ray diffraction study and magnetic measurements. The magnetic analysis concluded the negative Δ value (H = Δ(L - 2/3) + E(L - L) - (3/2)κλL·S + β[-(3/2)κL u + g e S u ]·H u (u = x, y, z)), and this was explained by the tetragonal elongation of the octahedral geometry. The magnetostructural correlation was ascertained by both the angular overlap model calculation and the density functional theory calculation.

An unusual Cu(ii) coordination polymer [Cu(Him) 2 (L)] (1) having a 4,4'-{[1,2-phenylene bis-(methylene)]bis(oxy)}dibenzoic acid ligand and an imidazole ligand possessing a 1D zig-zag chain was constructed and its magnetic behaviour was investigated, which indicated a magnetic phase transition below 25 K as well as long-range magnetic ordering.

To make a porous material with high magnetic ordering temperature is challenging because the low density of the material is adverse to the dense magnetic moment, a prerequisite to high-performance magnets. Herein, we report a hollow magnetic metal-organic framework (MMOF) [Co 3 (bpdc) 3 (tpt) 0.66 ] 1 (H 2 bpdc = 4,4'-biphenyldicarboxylic acid) with a Langmuir surface area of 1118 m 2 /g and spin-canted long-range magnetic ordering up to 22 K. Such a high performance is owing to the unique antiferromagnetic Kagomé lattice made of ferromagnetic Co 3 clusters and conjugated 2,4,6-tri(4-pyridinyl)-1,3,5-triazine (tpt) ligands, which is closely coupled with each other via double-interpenetration of the porous networks. Moreover, a parameter defined as the product of magnetic ordering/blocking temperature and the surface area for measuring the performance of porous molecular magnets is proposed.

An 80-year-old woman had an aortic valve replacement 1 month before admission and took warfarin for transient atrial fibrillation. She developed a disturbance of consciousness and left hemiplegia. On admission, the right radial artery was slightly palpable. Head MRI images showed a hyper-intense area in the right middle cerebral artery territory. MRA images showed an occlusion of the right M1 distal site and decreased signal at the right internal carotid artery. Contrast CT images of the ascending aorta showed an embolus in the innominate artery. She was diagnosed with an innominate artery saddle embolus and occlusion of the right cerebral artery due to cardiac embolism. She was treated with a heparin infusion and warfarin. She recovered consciousness and from hemiplegia gradually. Recanalization of the innominate artery and right cerebral artery was confirmed. In cases where the radial artery is slightly palpable, it is necessary to consider an innominate artery saddle embolus in addition to aortic dissection.

Magnetic properties of dinuclear nickel(II) complex [Ni 2 (sym-hmp) 2 ](BPh 4 ) 2 ·3.5DMF·0.5(2-PrOH) (1), where (sym-hmp) - is 2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate anion and DMF indicates dimethylformamide, were investigated using high-frequency and -field electron paramagnetic resonance (HFEPR). To magnetically characterize the mononuclear nickel(II) species forming the dimer, its two dinuclear zinc(II) analogues, [Zn 2 (sym-hmp) 2 ](BPh 4 ) 2 ·3.5DMF·0.5(2-PrOH) (2) and [Zn 2 (sym-hmp) 2 ](BPh 4 ) 2 ·2acetone·2H 2 O (2'), were prepared. One of them (2') was structurally characterized by X-ray diffractometry and doped with 5% mol nickel(II) ions to prepare a mixed crystal 3. From the HFEPR results on complex 1 obtained at 40 K, the spin Hamiltonian parameters of the first excited spin state (S = 1) of the dimer were accurately determined as |D 1 | = 9.99(2) cm -1 , |E 1 | = 1.62(1) cm -1 , and g 1 = [2.25(1), 2.19(2), 2.27(2)], and for the second excited spin state (S = 2) at 150 K estimated as |D 2 | ≈ 3.5 cm -1 . From these numbers, the single-ion zero-field splitting (ZFS) parameter of the Ni(II) ions forming the dimer was estimated as |D Ni | ≈ 10-10.5 cm -1 . The HFEPR spectra of 3 yielded directly the single-ion parameters for D Ni = +10.1 cm -1 , |E Ni | = 3.1 cm -1 , and g iso = 2.2. On the basis of the HFEPR results, the previously obtained magnetic data (Sakiyama, H.; Tone, K.; Yamasaki, M.; Mikuriya, M. Inorg. Chim. Acta 2011, 365, 183) were reanalyzed, and the isotropic interaction parameter between the Ni(II) ions was determined as J = -70 cm -1 (H ex = -J S A ·S B ). Finally, density functional theory calculations yielded the J value of -90 cm -1 in a qualitative agreement with the experiment.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic diseases, and results in the development of fibrosis. Oxidative stress is thought to be one of the underlying causes of NAFLD. Copper/zinc superoxide dismutase (SOD1) is a primary antioxidative enzyme that scavenges superoxide anion radicals. Although SOD1 knockout (KO) mice have been reported to develop fatty livers, it is not known whether this lack of SOD1 leads to the development of fibrosis. Since the accumulation of collagen typically precedes liver fibrosis, we assessed the balance between the synthesis and degradation of collagen in liver tissue from SOD1 KO mice. We found a higher accumulation of collagen in the livers of SOD1 KO mice compared to wild type mice. The level of expression of HSP47, a chaperone of collagen, and a tissue inhibitor (TIMP1) of matrix metalloproteinases (a collagen degradating enzyme) was also increased in SOD1 KO mice livers. These results indicate that collagen synthesis is increased but that its degradation is inhibited in SOD1 KO mice livers. Moreover, SOD1 KO mice liver sections were extensively modified by advanced glycation end products (AGEs), which suggest that collagen in SOD1 KO mice liver might be also modified with AGEs and then would be more resistant to the action of collagen degrading enzymes. These findings clearly show that oxidative stress plays an important role in the progression of liver fibrosis.

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Polarized neutron diffraction (PND) experiments were carried out at low temperature to characterize with high precision the local magnetic anisotropy in two paramagnetic high-spin cobalt(II) complexes, namely [Co(II) (dmf)6 ](BPh4 )2 (1) and [Co(II) 2 (sym-hmp)2 ](BPh4 )2 (2), in which dmf=N,N-dimethylformamide; sym-hmp=2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate, and BPh4 (-) =tetraphenylborate. This allowed a unique and direct determination of the local magnetic susceptibility tensor on each individual Co(II) site. In compound 1, this approach reveals the correlation between the single-ion easy magnetization direction and a trigonal elongation axis of the Co(II) coordination octahedron. In exchange-coupled dimer 2, the determination of the individual Co(II) magnetic susceptibility tensors provides a clear outlook of how the local magnetic properties on both Co(II) sites deviate from the single-ion behavior because of antiferromagnetic exchange coupling., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Copper/zinc superoxide dismutase (SOD1), a primary anti-oxidative enzyme, protects cells against oxidative stress. We report herein on a comparison of behavioral and neurobiological changes between SOD1 knockout (KO) and wild-type mice, in an attempt to assess the role of SOD1 in brain functions. SOD1 KO mice exhibited impaired motivational behavior in both shuttle-box learning and three-chamber social interaction tests. High levels of dopamine transporter protein and an acceleration of serotonin turnover were also detected in the cerebrums of the SOD1 KO mice. These findings suggest that SOD1 deficiency disturbs monoaminergic neurotransmission leading to a decrease in motivational behavior.

A large up-field shift (-763 ppm) has been observed for the carboxyl carbons of the dichlorido complex TBA[Ru(2)(O(2)CCH(3))(4)Cl(2)] (TBA(+) = tetra(n-butyl)ammonium cation) in the (13)C NMR spectrum (CD(2)Cl(2) at 25 °C). The DFT calculations showed spin delocalization from the paramagnetic Ru(2)(5+) core to the ligands, in agreement with the large up-field shift.

Two isoreticular metal-organic frameworks with chemical formulae [Cu(L)(4,4'-bipy)(H2O)]n 1.5nCH3CN (1) and [Cu(L)(4,4'-bipy)(H2O)]n·4nH2O (2) (H2L = diphenylmethane-4,4'-dicarboxylic acid) were synthesized and structurally characterized. They show the CdSO4 (6(5) 8) net and have an obvious 1D channel that is spread along the crystallographic c axis. More importantly, 1 shows high selectivity for H2 over N2 and CO2 at low pressure, which could be confirmed via computational calculations using the Connolly algorithm to reveal the size and shape of accessible voids. The incorporation of the drug 5-fluorouracil (5-FU) into the desolvated 1 was around 27.5 wt% per gram of the dehydrated 1. 5-FU is released in a highly controlled and progressive fashion with 61% of the drug released after 95 hours. In addition, we have applied molecular docking calculations to investigate the preferred conformation of 5-FU molecules upon binding to MOF 1. These calculations provide a structural basis to explain the 5-FU release from MOF 1.

Here we report a versatile magnetic susceptibility equation for tetranuclear octahedral high-spin cobalt(ii) complexes and a magnetic analysis for a tetranuclear defect cubane cobalt(ii) complex based on this equation. We concluded that the interaction is essentially ferromagnetic despite the decrease in the χT product on cooling from 300 K, and the decrease is due to the spin-orbit coupling.

Copper/zinc-superoxide dismutase knockout (SOD1 KO) mice have been extensively used as an experimental animal model of pathology associated with oxidative stress. The mice spontaneously develop mild chronic hemolytic anaemia (HA). We previously reported that the kidneys of these types of mice contain massive amounts of iron. In this study, to clarify the role of the kidney for iron metabolism under HA, changes in the levels of expression and functions of iron-related proteins were examined. In SOD1 KO mice kidneys, protein levels of iron transporters, the iron-responsive element (IRE)-binding activity of IRP1 and the levels of phosphorylation of IRP1 are all increased. These findings indicate that oxidative stress caused by a SOD1 deficiency probably enhances the phosphorylation of and the conversion of IRP1 to the IRE-binding form, which may accelerate the reabsorption of iron by renal tubular cells. Kidney could play an important role in iron homeostasis under conditions of HA.

The syntheses and structural properties of three dinuclear complexes [L(3)Co(μ(2)-O(2)P(Bn)(2))(3)CoL'][L"] [one ionic L(3) = py(3), L' = py, L" = ClO(4)(-) (1) and two molecular L(3) = py(3), L' = Cl (2) and L(3) = py, μ(2)-NO(3)(-), L' = py (3)] are reported. Complexes feature octahedral Co(II) sites bridged by three dibenzylphosphinate ligands to a tetrahedrally ligated Co(II) site, with the remaining coordination sites occupied by py, nitrato, and Cl ligands. The Co-Co distances are 4.248 Å at 291 K and 4.265 Å at 100 K for 1 and 4.278 and 4.0313(7) Å for 2 and 3, respectively at 100 K. A fit of the low-temperature magnetic susceptibility data was derived for complex 1 with g = 2.25, TIP = 700 × 10(-6) cm(3) mol (-1), λ = -173 cm(-1), κ = 0.93, ν = -3.9, Δ = 630 cm(-1), J = 0.15 cm(-1), and θ = -1.8 resulting in R(χ(M)) = 2.5 × 10(-5) and R(χ(M)T) = 5.8 × 10(-5).

The experimental charge-density distribution of the dinuclear cobalt(II) complex [Co(2)(sym-hmp)(2)](BPh(4))(2)·2H(2)O·2C(3)H(6)O was determined at 100 K. When decreasing the temperature, the magnetic susceptibility of this complex deviates from Curie law because of anti-ferromagnetic exchange interactions, but the susceptibility increases sharply at low temperature (< 20 K). To explain this magnetic behaviour a tilt angle between the Co-atom environments was previously theoretically predicted. The structure and experimental charge density determined in this study show a tilt angle. The calculated value, based on the 100 K experimental d-orbital model, is in agreement with the theoretical one.

Activated microglia produces inflammatory cytokines and nitric oxide (NO) that involved in neuronal injury and neurodegenerative diseases. We report herein, that H(2)O(2) intensifies the LPS-triggered expression of iNOS in the microglia cell line, BV-2, resulting in an enhancement in the production of NO. The NO production induced by a combination of LPS and H(2)O(2) was blocked by the addition of an anti-interferonβ (IFNβ) neutral antibody, suggesting that IFNβ levels are correlated with the LPS/H(2)O(2)-induced production of NO. However, although the expression of IFNβ was induced by H(2)O(2) treatment alone, neither the expression of iNOS mRNA nor the production of NO were induced. In addition, the expression of IFN receptor (IFNR) was induced by LPS but not by H(2)O(2). These data indicate that although H(2)O(2) alone cannot induce iNOS expression because of the insufficient expression of IFNR, in the presence of LPS, H(2)O(2) enhances iNOS expression via the expression of IFNβ. Our findings suggest that H(2)O(2) produced by activated microglia further enhances NO production in various inflammatory states., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The carbohydrate response element-binding protein (ChREBP) functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat. ChREBP is translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity. Although this glucose activation of ChREBP is generally observed only in liver cells, overexpression of wild type max-like protein X (Mlx), but not an inactive mutant Mlx, resulted in the exhibition of the ChREBP functions also in a human kidney cell line. Because high glucose conditions induce the glycosylation of cellular proteins, the effect of O-linked GlcNAc modification on ChREBP functions was examined. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which increases the O-linked GlcNAc modification of cellular proteins, caused an increase in the glucose response of ChREBP. In contrast, treatment with a glutamine fructose amidotransferase inhibitor (DON), which decreases O-GlcNAcylation by inhibiting the hexosamine biosynthetic pathway, completely blocked the glucose response of ChREBP. These results suggest that the O-linked glycosylation of ChREBP itself or other proteins that regulate ChREBP is essential for the production of functional ChREBP., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Copper/zinc-superoxide dismutase (SOD1) plays a protective role in cells by catalyzing the conversion of the superoxide anion into molecular oxygen and hydrogen peroxide. Although SOD1 knockout (KO) mice exhibit a reduced life span and an elevated incidence of dysfunctions in old age, young SOD1 KO mice grow normally and exhibit no abnormalities. This fact leads to the hypothesis that other antioxidative proteins prevent oxidative stress, compensating for SOD1. Differently expressed genes in 3-week-old SOD1 KO and littermate wild-type mice were explored. A gene remarkably elevated in SOD1 KO mouse kidneys was identified as the glutathione S-transferase Alpha 4 gene (Gsta4), which encodes the GSTA4 subunit. The GSTA4 protein level and activity were also significantly increased in SOD1 KO mouse kidneys. The administration of an iron complex, a free radical generator, induced GSTA4 expression in wild-type mouse kidneys. Iron deposition detected in SOD1 KO mouse kidney is thought to be an inducer of GSTA4. In addition, overexpression of mouse GSTA4 cDNA in human embryonic kidney cells decreased cell death caused by both 4-hydroxynonenal and hydrogen peroxide. These findings suggest that compensatory induced GSTA4 plays a protective role against oxidative stress in young SOD1 KO mouse kidneys.

Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of gene products involved in hepatic glycolysis and lipogenesis. Glucose affects the activity of ChREBP largely through post-translational mechanisms involving phosphorylation-dependent cellular localization. In this work we show that the N-terminal region of ChREBP (residues 1-251) regulates its subcellular localization via an interaction with 14-3-3. 14-3-3 binds an alpha-helix in this region (residues 125-135) to retain ChREBP in the cytosol, and binding of 14-3-3 is facilitated by phosphorylation of nearby Ser-140 and Ser-196. Phosphorylation of ChREBP at these sites was essential for its interaction with CRM1 for export to the cytosol, whereas nuclear import of ChREBP requires dephosphorylated ChREBP to interact with importin alpha. Notably, 14-3-3 appears to compete with importin alpha for ChREBP binding. 14-3-3beta bound to a synthetic peptide spanning residues 125-144 and bearing a phosphate at Ser-140 with a dissociation constant of 1.1 microm, as determined by isothermal calorimetry. The interaction caused a shift in the fluorescence maximum of the tryptophan residues of the peptide. The corresponding unphosphorylated peptide failed to bind 14-3-3beta. These results suggest that interactions with importin alpha and 14-3-3 regulate movement of ChREBP into and out of the nucleus, respectively, and that these interactions are regulated by the ChREBP phosphorylation status.

Background: Inducible co-stimulator (ICOS) is a co-stimulatory receptor on activated T cells that provides the signals needed for Th1 and Th2 responses via its interaction with B7h. Chronic focal infections are closely related to pustulosis palmaris et plantaris (PPP), but the involvement of ICOS in PPP has not been clarified., Objective: To investigate the effectiveness of treatments for focal infections on PPP skin lesions and the involvement of ICOS-positive T cells at focal infection sites in the tonsils and in PPP lesional skin., Methods: In patients that had undergone a tonsillectomy or dental treatment, the clinical activities of PPP, both the skin lesions and pustulotic arthro-osteitis were followed for over 2 years. The expressions of ICOS and various other activation markers on T cells were examined in tonsil tissue from both PPP patients and non-PPP patients, and the expression levels in peripheral blood were also evaluated in PPP patients and healthy donors. ICOS-positive T cells and B7h expression in PPP and normal skin were examined immunohistochemically., Results: The above treatments for focal infections led to a dramatic and persistent improvement in the PPP skin lesions and pustulotic arthro-osteitis. The expression of ICOS, but not of other activation markers, was higher in tonsil tissues from PPP patients than in tonsil tissues from non-PPP patients. B7h was upregulated without numerous ICOS-positive T cell infiltrates in the skin lesions., Conclusion: The activation of T cells via ICOS co-stimulation in focal infections likely triggers the skin and skeletal inflammation associated with PPP, resulting in tissue damage.

Clinically apparent mumps reinfection is considered extremely rare, but several cases have been suspected of reinfection in an out-patient clinic. In this study, virological examination, virus isolation, the reverse transcription loop-mediated isothermal amplification (RT-LAMP), and IgG and IgM EIA antibodies, were examined in order to identify mumps reinfection. Patients were divided into three categories; the reinfection group comprised 29 patients with a history of natural infection, the vaccine-failure group consisted of 37 patients with an immunization history, and two patients had histories of both immunization and mumps infection. Another 25 patients were enrolled as a primary infection group. Mumps virus was isolated in 5 (17%) and the genome was detected in 12 (41%) of 29 in the reinfection group. Reinfection was confirmed in 21/28, demonstrating high avidity of IgG EIA. Mumps virus was isolated in 15 (41%) and there was a higher positivity of genome amplification in 25 (68%) of 37 patients in the vaccine-failure group. Among these, 23 were confirmed as secondary vaccine failure by high avidity IgG EIA serology. In the primary infection group, the isolation rate and genome detection rate was higher in 16 (64%) and in 18 (72%) of 25 patients, respectively. There was no significant difference in virus load among the three groups but high mumps virus load was suspected in the IgM EIA-positive group based on the shorter amplification time on RT-LAMP. Mumps virus reinfection was confirmed by RT-LAMP and an IgG avidity test and was not a rare event.

The hydrothermal reaction of 2-pyrimidine-carboxamide, CoCl2.6H(2)O and K3[Co(CN)6] affords a novel mixed-valence Co(II)/Co(III) 3D complex K[Co3(CN)6(ox)(H(2)O)2].H2O, which contains cyano-bridged Co(7) defective cubanes connected by oxalate and cyanide bridging groups and behaves as a canted antiferromagnet with Tc = 17.5 K.

To compare the incidence of aseptic meningitis associated with symptomatic natural mumps infection and in mumps vaccine recipients, we conducted a prospective comparative study. Consecutive samples of 1051 children with mumps were enrolled by 10 pediatricians and 21,465 vaccine recipients by 143 pediatric primary care practitioners, from January 1, 2000 to January 1, 2003. Parents used a daily diary to record symptoms during the period of illness (15 days) or 30-day period following immunization. Mumps infection was confirmed by virus isolation and/or detection of mumps virus genome in salivary and CSF samples. The incidence of aseptic meningitis was 13/1051 (1.24%) in patients with symptomatic natural mumps infection and was estimated to be 0.7-1.1% of overall infection in considering asymptomatic infection, and 10/21,465 (0.05%) in vaccine recipients. Although aseptic meningitis is a clear side effect of the mumps vaccine, the incidence is considerably lower than among those with symptomatic natural infection. Our results provide an informative data for consideration to resume mumps vaccine as a part of routine immunization schedule for Japanese children.

The isomorphous coordination polymers {micro-Au(CN)(2)](2)[(M(NH(3))(2))(2)(mu-bpym)]}[Au(CN)(2)](2) (M = Co(II) (1), Ni(II) (2), Cu(II) (3)) have been prepared from the reaction of 2 equiv. M(NO(3))(2) x nH(2)O (M = Cu(II), n = 3; M = Ni(II) and Co(II), n = 6) with 1 equiv. of bipyrimidine (bpym) in aqueous ammonia and then with an aqueous solution containing 1 equiv. of K[Au(CN)(2)]. The structures of these complexes are made of bpym bridged centrosymmetric dinuclear [M(NH(3))(2)(mu-bpym)M(NH(3))(2)] units connected by [Au(CN)(2)](-) anions to four other dinuclear units giving rise to a cationic 2D (4,4) rectangular grid network, its charge being balanced by two non-coordinated [Au(CN)(2)](-). The layers are stacked in such a way that the ammonia coordinated molecules are interdigitated and aligned above and below one sheet with cavities in neighbouring sheets, giving rise to an ABAB[dot dot dot] repeat pattern of layers. Gold atoms of bridging and non-bridging dicyanoaurate anions are involved in short aurophilic interactions (Au1-Au2 distances in the range 3.12-3.14 Angstrom), leading to a chain of gold atoms running along the a direction. Neighbouring gold chains are further connected by weaker aurophilic interactions (Au1-Au1 distances in the range 3.43-3.49 Angstrom), affording a honeycomb-like 2D network of gold atoms. The (4,4) rectangular sheets and (6,3) honeycomb sheets share the Au2 atoms, leading to a unique 3D network. Magnetic measurements clearly show the existence of antiferromagnetic exchange coupling between the metal ions with susceptibility maxima at 17 K (1), 22 K (2), and 17 K (3). The data of 1 were analyzed through a full Hamiltonian involving spin-orbit coupling, axial distortion, Zeeman interactions and magnetic exchange coupling between Co(II), and the best fit gives J = -9.23 cm(-1), kappa = 0.99, lambda = -142 cm(-1), Delta = -562 cm(-1). For 2 and 3, magnetic data were fitted to the theoretical equations derived from the isotropic Hamiltonian: H = -JS(1)S(2). The best fit parameters were g = 2.050(1), J = -17.51(1) and P = 0.01(2) for 2 and g = 2.068(5), J = -20.07(8) and P = 0.015(4) for 3, respectively (P takes into account the amount of paramagnetic impurity). In order to explain the weak magnetic interaction between copper(II) ions mediated by the bipyrimidine bridging ligand in 3, we have carried out electronic structure calculations based on the density functional theory (DFT).

During the 2000/2001 influenza season in Japan, children ranging in age from 6 months to 13 years with fever exceeding 37.5 degrees C were recruited. Vaccine efficacy was evaluated by comparing the rates of pre-seasonal vaccination between groups stratified by fever severity. Seven hundred and sixty one patients (33.1%), culture positive for influenza were enrolled for analysis. The numbers of patients for A/H1N1 and A/H3N2 were insufficient for statistical analysis. For influenza B the odds ratio for vaccinated children to have a maximum fever exceeding 39.5 degrees C was 0.52 (95% CI, 0.30-0.92) Our findings suggest modest impact of influenza vaccination on limiting severity of disease symptoms.

alpha1,6-Fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue from GDP-fucose to the innermost N-acetylglucosamine residue of N-glycans. Here we report that the loss of core fucosylation impairs the function of low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), a multifunctional scavenger and signaling receptor, resulting in a reduction in the endocytosis of insulin like growth factor (IGF)-binding protein-3 (IGFBP-3) in the cells derived from Fut8-null (Fut8-/-) mice. The reduced endocytosis was restored by the re-introduction of Fut8. Serum levels of IGFBP-3 were markedly upregulated in Fut8-/- mice. These data clearly indicate that core fucosylation is crucial for the scavenging activity of LRP-1 in vivo.

3-Deoxyglucosone (3-DG), a dicarbonyl compound produced by glycation, plays a role in the modification and cross-linking of long-lived proteins. We synthesized [3H]3-DG from [3H]glucose and developed an internalization assay system using HPLC to examine its cellular metabolism. When smooth muscle cells or human umbilical vein endothelial cells were incubated with [3H]3-DG, it was found that [3H]3-DG was internalized by cells in a time dependent manner. The rate of internalization was reduced when the cells were incubated at 4 degrees C or treated with phenylarsine oxide (PAO). By monitoring [3H]3-DG taken up by cells, it was confirmed that 3-DG is reduced to 3-deoxyfructose (3-DF) and that this reaction was inhibited by an aldo-keto reductase inhibitor (ARI). The presence of 3-DG led to an increase in reactive oxygen species levels in the cells and subsequent apoptosis, and the effect was enhanced by pretreatment with ARI. These results suggest that 3-DG is internalized by cells and reduced to 3-DF by aldo-keto reductases, and that the internalized 3-DG is responsible for the production of intracellular oxidative stress.

Toll-like receptor 3 (TLR3) recognizes dsRNA of viral origin and polyriboinosine-polyribocytidylic acid (poly (I:C)). TLR3 mediates the activation of IRF-3 and NF-kappaB and thereby the secretion of type I interferons and inflammatory cytokines. However, the mechanism of this activation is poorly understood. To study the molecular recognition events and biochemical interactions between TLR3 and dsRNA, human TLR3 ectodomain (ECD) fused with a signal peptide at the N-terminus and 6 x His-tag at the C-terminus (TLR3-ECD) was obtained by the baculovirus expression system. To examine the various nucleic acids binding to TLR3-ECD in vitro, a filter binding assay was carried out at pH 4.2-7.6. Interaction of TLR3-ECD with various nucleic acids (particularly dsRNA, in vitro transcripts of tRNA and HCV NS3 aptamer) required an acidic pH.