Some properties and applications of the transglutaminase (TGase) referred to as microbial TGase (MTGase), derived from a variant of Streptomyces mobaraensis (formerly classified as ...Streptoverticillium mobaraense), are described. MTGase cross-linked most food proteins, such as caseins, soybean globulins, gluten, actin, myosins, and egg proteins, as efficiently as mammalian TGases by forming an epsilon-(γ-glutamyl)lysine bond. However, unlike many other TGases, MTGase is calcium-independent and has a relatively low molecular weight. Both of these properties are of advantage in industrial applications; a number of studies have illustrated the potential of MTGase in food processing and other areas. The crystal structure of MTGase has been solved. It provides basic structural information on the MTGase and accounts well for its characteristics. Moreover, an efficient method for producing extracellular MTGase has been established using Corynebacterium glutamicum. MTGase may be expected to find many uses in both food and non-food applications.
The authors evaluated the feasibility of MR permeability imaging by comparison with 11C-methionine-PET, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumors in 15 patients ...with 18 lesions following gamma knife radiosurgery. The area under the ROC curve for differentiating radiation necrosis from recurrent tumors was the best for the 11C-methionine ratio (0.90) followed by the contrast-enhancement ratio (0.81), maximum slope of increase (millimole/second) (0.80), and the initial area under the signal intensity–time curve (0.78). They conclude that PET using 11C-methionine may be superior to MR permeability imaging, ADC, and FDG-PET for differentiating radiation necrosis from recurrent tumors after gamma knife radiosurgery for metastatic brain tumors. BACKGROUND AND PURPOSE: In patients with metastatic brain tumors after gamma knife radiosurgery, the superiority of PET using 11C-methionine for differentiating radiation necrosis and recurrent tumors has been accepted. To evaluate the feasibility of MR permeability imaging, it was compared with PET using 11C-methionine, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumors. MATERIALS AND METHODS: The study analyzed 18 lesions from 15 patients with metastatic brain tumors who underwent gamma knife radiosurgery. Ten lesions were identified as recurrent tumors by an operation. In MR permeability imaging, the transfer constant between intra- and extravascular extracellular spaces (/minute), extravascular extracellular space, the transfer constant from the extravascular extracellular space to plasma (/minute), the initial area under the signal intensity–time curve, contrast-enhancement ratio, bolus arrival time (seconds), maximum slope of increase (millimole/second), and fractional plasma volume were calculated. ADC was also acquired. On both PET using 11C-methionine and FDG-PET, the ratio of the maximum standard uptake value of the lesion divided by the maximum standard uptake value of the symmetric site in the contralateral cerebral hemisphere was measured (11C-methionine ratio and FDG ratio, respectively). The receiver operating characteristic curve was used for analysis. RESULTS: The area under the receiver operating characteristic curve for differentiating radiation necrosis from recurrent tumors was the best for the 11C-methionine ratio (0.90) followed by the contrast-enhancement ratio (0.81), maximum slope of increase (millimole/second) (0.80), the initial area under the signal intensity–time curve (0.78), fractional plasma volume (0.76), bolus arrival time (seconds) (0.76), the transfer constant between intra- and extravascular extracellular spaces (/minute) (0.74), extravascular extracellular space (0.68), minimum ADC (0.60), the transfer constant from the extravascular extracellular space to plasma (/minute) (0.55), and the FDG-ratio (0.53). A significant difference in the 11C-methionine ratio (P < .01), contrast-enhancement ratio (P < .01), maximum slope of increase (millimole/second) (P < .05), and the initial area under the signal intensity–time curve (P < .05) was evident between radiation necrosis and recurrent tumor. CONCLUSIONS: The present study suggests that PET using 11C-methionine may be superior to MR permeability imaging, ADC, and FDG-PET for differentiating radiation necrosis from recurrent tumors after gamma knife radiosurgery for metastatic brain tumors.
Conceptualised in 1920s Japan by Yanagi Sôetsu, the Mingei movement has spread world wide since the 1950s, creating phenomena as diverse as Mingei museums, Mingei connoisseurs and collectors, Mingei ...shops and Mingei restaurants. The theory, at its core and its adaptation by Bernard Leach, has long been an influential 'Oriental' aesthetic for studio craft artists in the West. But why did Mingei become so particularly influential to a western audience? And could the 'Orientalness' perceived in Mingei theory be nothing more than a myth? This richly illustrated work offers controversial new evidence through its cross-cultural examination of a wide range of materials in Japanese, English, Korean and Chinese, bringing about startling new conclusions concerning Japanese modernization and cultural authenticity. This new interpretation of the Mingei movement will appeal to scholars of Japanese art history as well as those with interests in cultural identity in non-Western cultures.
Abstract
Background
PAS biopolymers are recombinant polypeptides comprising the small uncharged
l
-amino acids Pro, Ala and/or Ser which resemble the widely used poly-ethylene glycol (PEG) in terms ...of pronounced hydrophilicity. Likewise, their random chain behaviour in physiological solution results in a strongly expanded hydrodynamic volume. Thus, apart from their use as fusion partner for biopharmaceuticals to achieve prolonged half-life in vivo, PAS biopolymers appear attractive as substitute for PEG—or other poorly degradable chemical polymers—in many areas. As a prerequisite for the wide application of PAS biopolymers at affordable cost, we have established their highly efficient biotechnological production in
Corynebacterium glutamicum
serving as a well characterized bacterial host organism.
Results
Using the CspA signal sequence, we have secreted two representative PAS biopolymers as polypeptides with ~ 600 and ~ 1200 amino acid residues, respectively. Both PAS biopolymers were purified from the culture supernatant by means of a simple downstream process in a truly monodisperse state as evidenced by ESI–MS. Yields after purification were up to ≥ 4 g per liter culture, with potential for further increase by strain optimization as well as fermentation and bioprocess development. Beyond direct application as hydrocolloids or to exploit their rheological properties, such PAS biopolymers are suitable for site-specific chemical conjugation with pharmacologically active molecules via their unique terminal amino or carboxyl groups. To enable the specific activation of the carboxylate, without interference by the free amino group, we generated a blocked N-terminus for the PAS(1200) polypeptide simply by introducing an N-terminal Gln residue which, after processing of the signal peptide, was cyclised to a chemically inert pyroglutamyl group upon acid treatment. The fact that PAS biopolymers are genetically encoded offers further conjugation strategies via incorporation of amino acids with reactive side chains (e.g., Cys, Lys, Glu/Asp) at defined positions.
Conclusions
Our new PAS expression platform using Corynex
®
technology opens the way to applications of PASylation
®
technology in multiple areas such as the pharmaceutical industry, cosmetics and food technology.
•We study crystal structure of higher manganese silicide (HMS) at high temperature.•The amount of secondary MnSi phase exceeds that of HMS phase above ∼1133 K.•Thermal expansion coefficients are ...almost the same as some typical metals.•(3+1)-Dimensional superspace approach reveals compositional change of HMS.•The Si composition γ decreases with temperature above 773 K.
The (3+1)-dimensional crystal structure of a higher manganese silicide (MnSiγ) phase is revealed using in situ high temperature powder X-ray diffraction (XRD) above room temperature. The compound consists of two tetragonal subsystems of Mn and Si with an irrational c-axis ratio γ=cMn/cSi. The in situ XRD results show that the MnSiγ phase is stable, in a vacuum of ∼1 Pa, up to 1093 K and partially decomposes into the monosilicide (MnSi) phase with further increase in temperature. Refined a- and cMn-axis lengths increase linearly and the thermal expansion coefficients are comparable with those of typical metallic electrode materials. In contrast, cSi-axis length changes its increment against temperature at TBD ∼773 K. As a result, the temperature dependence of γ starts to decrease gradually above TBD, from 1.7387(1) (at 773 K) to 1.7244(1) (at 1173 K). This finding implies that the MnSiγ phase consecutively changes its irrational composition above TBD, a typical temperature where the silicides exhibit a maximum figure-of-merit. An increase in hole carrier concentration is expected according to the valence electron counting concept. Although the nearest Mn–Mn and Mn–Si distances increase monotonically with temperature, the nearest Si–Si distance much increases by ∼0.05 Åfrom 2.439(4) Åat 773 K to 2.493(7) Åat 1173 K. The latter increase is considered to be caused by the introduction of excited electron carriers into the anti-bonding orbital, due to the bipolar diffusion (BD).
Aims/hypothesis
Medical nutrition therapy plays a critical role in the prevention and treatment of type 2 diabetes. However, appropriate measures of eating behaviours, such as eating rate, have not ...yet been clearly established. The aim of the present study was to examine the associations among eating rate, obesity and cardiovascular risk factors.
Methods
A total of 7,275 Japanese individuals aged ≥40 years who had normal fasting glucose levels, impaired fasting glucose or diabetes were divided into four groups according to self-reported eating rate: slow, medium, relatively fast and very fast. The associations between eating rate and various cardiovascular risk factors were investigated cross-sectionally.
Results
The proportions of participants who were obese or who had elevated waist circumference levels increased progressively with increases in eating rate (
p
for trend <0.001), regardless of glucose tolerance status. These associations remained significant after adjustment for potential confounders, namely, age, sex, total energy intake, dietary fibre intake, current smoking, current drinking and regular exercise (
p
for trend <0.001). Blood pressure and lipid levels also tended to increase in association with eating rate. HbA
1c
rose significantly as eating rate increased, even after multivariate adjustment, including BMI, in diabetic patients on insulin therapy (
p
= 0.02), whereas fasting plasma glucose did not increase significantly.
Conclusions/interpretation
Our findings suggest that eating rate is associated with obesity and other cardiovascular risk factors and therefore may be a modifiable risk factor in the management of cardiovascular risk factors and diabetes.
Objectives Multidrug-resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in hospitals, especially in patients on ventilators. Recent data demonstrate that colistin may be effective ...for these patients, although limited in vitro and in vivo data are available. Our aim was to identify further characteristics of colistin for the therapy of pneumonia caused by MDRP. Methods The effects of colistin on clinical strains of MDRP were examined by susceptibility test, time–kill assay, lipopolysaccharide (LPS)-blocking assay and a mouse pneumonia model, alone or in combination with other antibiotics. For the pneumonia model, mice were intranasally infected with bacteria and kept in hyperoxic conditions to mimic ventilator-associated pneumonia. Results As a single agent, colistin exhibited the strongest activity of the antimicrobial agents tested. In combination, maximum synergy was observed with colistin plus rifampicin. As expected, co-incubation of bacterial culture supernatants with colistin significantly reduced LPS activities with an associated decrease in cellular cytotoxicity. In the pneumonia model, intranasal, but not intravenous, colistin combined with rifampicin produced maximum survival protection. Pharmacokinetic analysis of colistin demonstrated the superiority of intranasal administration, judging from the compartmentalized high concentration and the long half-life in the lungs. Moreover, colistin therapy significantly decreased both production of inflammatory cytokines and LPS activity, even at a dose effecting no change in the bacterial burden in the lung. Conclusions These data strongly suggest that colistin may be an important option for combination therapy against critical MDRP infections. For pneumonia especially, intranasal colistin with rifampicin may be beneficial not only for synergistic antibacterial activity, but also for blocking LPS.
The urocortin (UCN) group of neuropeptides includes urocortin 1/sauvagine/urotensin 1 (UTS1), urocortin 2 (UCN2) and urocortin 3 (UCN3). In recent years, evidence has accumulated showing that UCNs ...play pivotal roles in mediating stress response and anxiety in mammals. Evidence has also emerged regarding the evolutionary conservation of UCNs in vertebrates, but very little information is available about UCNs in non‐mammalian vertebrates. Indeed, at present, there are no reports of the empirical identification of ucn2 in non‐mammalian vertebrates or of the distribution of ucn2 and ucn3 expression in the adult central nervous system (CNS) of these animals. To gain insight into the evolutionary nature of UCNs in vertebrates, we cloned uts1, ucn2 and ucn3 in a teleost fish, medaka and examined the spatial expression of these genes in the adult brain and spinal cord. Although all known UCN2 genes except those in rodents have been reported to likely lack the necessary structural features to produce a functional pre‐pro‐protein, all three UCN genes in medaka, including ucn2, displayed all of these features, suggesting their functionality. The three UCN genes exhibited distinct spatial expression patterns in the medaka brain: uts1 was primarily expressed in broad regions of the dorsal telencephalon, ucn2 was expressed in restricted regions of the thalamus and brainstem and ucn3 was expressed in discrete nuclei throughout many regions of the brain. We also found that these genes were all expressed throughout the medaka spinal cord, each with a distinct spatial pattern. Given that many of these regions have been implicated in stress responses and anxiety, the three UCNs may serve distinct physiological roles in the medaka CNS, including those involved in stress and anxiety, as shown in the mammalian CNS.
IVL is characterized by a propensity for intravascular tumor cell proliferation. Premortem diagnosis of IVL is difficult because of its nonspecific clinical, laboratory, and imaging manifestations. ...This study examined cerebral MR imaging patterns of IVL and their changes with and without chemotherapy. Nine of 11 patients studied presented with abnormal findings. We define 5 patterns of abnormal MR imaging findings: 1) infarctlike lesions, 2) nonspecific white matter lesions, 3) meningeal enhancement, 4) masslike lesions, and 5) hyperintense lesions in the pons on T2WI. Seven patients presented with only 1 pattern, while 2 patients presented with multiple patterns. Lesions in 7 treated patients responded to chemotherapy. Pathologic specimens revealed intravascular tumor cell infiltration with associated infarctions, necrosis, congestion, demyelination, vasculitis, and tumor cell extravasation. We conclude that MR imaging patterns can be possible manifestations of intravascular-dominant infiltration by tumor cells with associated occlusion or inflammation, depending on the level of affected vessels.
Background. Little information is available on the incidence of renal stones with ritonavir-boosted atazanavir (ATV/r) use. Methods. In a single-center study, the incidence of renal stones was ...compared between human immunodeficiency virus (HIV)—infected patients who commenced ritonavir-boosted atazanavir (ATV/r)—containing antiretroviral (ARV) therapy (the ATV/r group) and those who were receiving other protease inhibitors (the other PIs group). The effects of ATV/r were estimated by univariate and multivariate Cox proportional hazards regression models. Other possible risk factors were evaluated by univariate analysis, and those found to be significant were entered into multivariate analysis. Results. Renal stones were diagnosed in 31 patients (23.7 cases per 1000 person-years) in the ATV/r group (n = 465) and 4 in patients (2.2 cases per 1000 person-years) in the other PIs group (n = 775). ATV/r use was significantly associated with renal stones, by univariate and multivariate analyses (adjusted hazard ratio, 10.44; 95% confidence interval CI, 3.685–29.59; P < .001). ATV/r remained a significant risk factor for renal stones in all subgroups stratified by the median values of baseline variables. In the 31 patients receiving ATV/r who developed renal stones, the median time from commencement of ATV/r to diagnosis was 24.5 months (interquartile range, 14.7–34.6 months). Of the 18 patients who continued ATV/r despite the diagnosis of renal stones, 6 (33.3%) experienced recurrence. No patient who discontinued ATV/r experienced recurrence during the observation period (250.6 person-months). Conclusions. The incidence of renal stones was substantially higher among patients in the ATV/r group, compared with patients in the other PIs group. Continuation of ATV/r after diagnosis of renal stones was associated with a high rate of recurrence. Switching ATV/r to other ARVs is warranted in patients who develop renal stones.
PDF
