The main target of this work is to examine blood clearance and external exposure for 177Lu-DOTATATE compared with new emerging 177Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5?±?1.1 GBq 177Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq 177Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver’s cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4–5 days and medical staff’s dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to 177Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0?±?2.8 and 2?±?1.9 µSv/(h GBq), respectively, while those due to 177Lu-PSMA were 3.1?±?0.8 and 2.2?±?0.9 µSv/(h GBq). Total effective dose of 17 caregivers was 100–200 µSv for 177Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 µSv per patient, respectively, while those for physicists and physicians were 2 µSv per patient. For 177Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31?±?0.13 and 4.5?±?1 h, while they were found as 0.4?±?0.1 and 5?±?1 h, respectively, for 177Lu-PSMA. The first micturition time following 177Lu-DOTATATE infusion was noted after 36?±?14 min, while the second and third voiding times were after 74?±?9 and 128?±?41 min, respectively. It is concluded that blood clearance and radiation exposure for 177Lu-DOTATATE are very similar to those for 177Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 µSv/(h GBq)] decreased below the dose rate that allows release of the patient from the hospital (20 µSv/h) after 6 h at 1 m distance. 相似文献
This study aimed to overexpress a glucose oxidase gene (GOD1) in Aureobasidium sp. P6 to achieve Ca2+-gluconic acid (GA) overproduction. The GOD1 gene was cloned, deleted, and overexpressed. A protein deduced from the GOD1 gene of Aureobasidium sp. P6 strain had 1824 bp that encoded a protein with 606 amino acids, with a conserved NADB-ROSSMAN domain and a GMC-oxred domain. Deleting the GOD1 gene made the disruptant GOK1 completely lose the ability to produce GA and GOD1 activity, whereas overexpressing the GOD1 gene rendered the transformant GOEX8 to produce considerably more Ca2+-GA (160.5?±?5.6 g/L) and higher GOD1 activity (1438.6?±?73.2 U/mg of protein) than its parent P6 strain (118.7?±?4.3 g/L of Ca2+-GA and 1100.0?±?23.6 U/mg of GOD1 protein). During a 10-L fermentation, the transformant GOEX8 grown in the medium containing 160.0 g/L of glucose produced 186.8?±?6.0 g/L of Ca2+-GA, the yield was 1.2 g/g of glucose, and the volumetric productivity was 1.7 g/L/h. Most of the produced GOD1 were located in the yeast cell wall. The purified product was identified to be a GA. The transformant GOEX8 overexpressing the GOD1 gene could produce considerably more Ca2+-GA (186.8?±?6.0 g/L) than its wild-type strain P6. 相似文献
The novel species Sporolactobacillus pectinivorans GD201205T can produce lactic acid and aromatic compounds such as isoamyl acetate and phenethyl acetate. To characterize this strain, we sequenced the whole genome of S. pectinivorans GD201205T and determined that it contains a 3,926,837-bp chromosome with a GC content of 44.27%, 4320 genes, 64 tRNAs, 14 rRNAs, and four sRNAs. The identification of the gene sequence of S. pectinivorans GD201205T provides a basis for understanding its molecular genetics and features, which in turn will facilitate its potential application as a starter culture in the food processing industry. 相似文献
Performance of 18 DFT functionals (B1B95, B3LYP, B3PW91, B97D, BHandHLYP, BMK, CAM-B3LYP, HSEh1PBE, M06-L, mPW1PW91, O3LYP, OLYP, OPBE, PBE1PBE, tHCTHhyb, TPSSh, wB97xD, VSXC) in combinations with six basis sets (cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, aug-cc-pVTZ, IGLO-II, and IGLO-III) and three methods for calculating magnetic shieldings (GIAO, CSGT, IGAIM) was tested for predicting 1H and 13C chemical shifts for 25 organic compounds, for altogether 86 H and 88 C atoms. Proton shifts varied between 1.03 ppm to 12.00 ppm and carbon shifts between 7.87 ppm to 209.28 ppm. It was found that the best method for calculating 13C shifts is PBE1PBE/aug-cc-pVDZ with CSGT or IGAIM approaches (mae?=?1.66 ppm), for 1H the best results were obtained with HSEh1PBE, mPW1PW91, PBE1PBE, CAM-B3LYP, and B3PW91 functionals with cc-pVTZ basis set and with CSGT or IGAIM approaches (mae?=?0.28 ppm). We found that often larger basis sets do not give better results for chemical shifts. The best basis sets for calculating 1H and 13C chemical shifts were cc-pVTZ and aug-cc-pVDZ, respectively. CSGT and IGAIM NMR approaches can perform really well and are in most cases better than popular GIAO approach.
Graphical Abstract Mean absolute errors for 1H and 13C chemical shifts and computational times of neutral toluene molecule with aug-cc-pVDZ basis set and CSGT approach
Vibrio cholerae is the bacterial causative agent of the human disease cholera. Non-pathogenic bacterium can be converted to pathogenic following infection by a filamentous phage, CTXΦ, that carries the cholera toxin encoding genes. A crucial step during phage infection requires a direct interaction between the CTXΦ minor coat protein (pIIICTX) and the C-terminal domain of V. cholerae TolA protein (TolAIIIvc). In order to get a better understanding of TolA function during the infection process, we have initiated a study of the V. cholerae TolAIII domain by 2D and 3D heteronuclear NMR. With the exception of the His-tag (H123–H128), 97 % of backbone 1H, 15N and 13C resonances were assigned and the side chain assignments for 92 % of the protein were obtained (BMRB deposit with accession number 25689). 相似文献
The transforming growth factor beta induced protein (TGFBIp) is a major protein component of the human cornea. Mutations occurring in TGFBIp may cause corneal dystrophies, which ultimately lead to loss of vision. The majority of the disease-causing mutations are located in the C-terminal domain of TGFBIp, referred as the fourth fascilin-1 (FAS1-4) domain. In the present study the FAS1-4 Ala546Thr, a mutation that causes lattice corneal dystrophy, was investigated in dimethylsulfoxide using liquid-state NMR spectroscopy, to enable H/D exchange strategies for identification of the core formed in mature fibrils. Isotope-labeled fibrillated FAS1-4 A546T was dissolved in a ternary mixture 95/4/1 v/v/v% dimethylsulfoxide/water/trifluoroacetic acid, to obtain and assign a reference 2D 1H–15N HSQC spectrum for the H/D exchange analysis. Here, we report the near-complete assignments of backbone and aliphatic side chain 1H, 13C and 15N resonances for unfolded FAS1-4 A546T at 25 °C. 相似文献
This research aimed to evaluate the capacity of acid-resistant purple nonsulfur bacteria, Rhodopseudomonas palustris strains VNW02, TLS06, VNW64, and VNS89, to resist Al3+ and Fe2+ and to investigate their potential to remove both metals from aqueous solutions using exopolymeric substances (EPS) and biomasses. Based on median inhibition concentration (IC50), strain VNW64 was the most resistant to both metals under conditions of aerobic dark and microaerobic light; however, strain TLS06 was more resistant to Al3+ under aerobic dark conditions. High metal concentrations resulted in an altered cellular morphology, particularly for strain TLS06. Metal accumulation in all tested PNSB under both incubating conditions as individual Al3+ or Fe2+ was in the order of cell wall?>?cytoplasm?>?cell membrane. This was also found in a mixed metal set only under conditions of aerobic dark as microaerobic light was in the degree of cytoplasm?>?cell wall?>?cell membrane. Of all strains tested, EPS from strain VNW64 had the lowest carbohydrate and the highest protein contents. Metal biosorption under both incubating conditions, EPS produced by strains VNW64 and TLS06, achieved greater removal (80 mg Al3+ L?1 and/or 300 mg Fe2+ L?1) than their biomasses. Additionally, strain VNW64 had a higher removal efficiency compared to strain TLS06. Based on the alteration in cellular morphology, including biosorption and bioaccumulation mechanisms, R. palustris strains VNW64 and TLS06 demonstrated their resistance to metal toxicity. Hence, they may have great potential for ameliorating the toxicity of Al3+ and Fe2+ in acid sulfate soils for rice cultivation. 相似文献
The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na+/K+-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150–200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the α1 subunit of Na+/K+-ATPase by 30% (p < 0.05), expression of total α1 subunit of Na+/K+-ATPase by 31% (p < 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p < 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p < 0.01) and 62% (p < 0.05), respectively. Our results suggest that a HF diet alters cardiac Na+/K+-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats. 相似文献
A novel bacterium, strain 1ZS3-15T, was isolated from rhizosphere of rice. Its taxonomic position was investigated using a polyphasic approach. The novel strain was observed to be Gram-stain positive, spore-forming, aerobic, motile and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 1ZS3-15T was recovered within the genus Paenibacillus. It is closely related to Paenibacillus pectinilyticus KCTC 13222T (97.9 % similarity), Paenibacillus frigoriresistens CCTCC AB 2011150T (96.8 %), Paenibacillus alginolyticus JCM 9068T (96.4 %) and Paenibacillus chondroitinus DSM 5051T (95.5 %). The fatty acid profile of strain 1ZS3-15T, which showed a predominance of anteiso-C15:0 and iso-C16:0, supported the allocation of the strain into the genus Paenibacillus. The predominant menaquinone was found to be MK-7. The polar lipids profile of strain 1ZS3-15T was found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified lipid and two unidentified aminophospholipids. The cell wall peptidoglycan contains meso-diaminopimelic acid. Based on draft genome sequences, the DNA–DNA relatedness between strain 1ZS3-15T and the closely related species P. pectinilyticus KCTC 13222T are 24.2 ± 1.0 %, and the Average Nucleotide Identity values between the strains are 78.9 ± 0.1 %, which demonstrated that this isolate represents a new species in the genus Paenibacillus. The DNA G+C content was determined to be 45.3 mol%, which is within the range reported for Paenibacillus species. Characterisation by genotypic, chemotaxonomic and phenotypic analysis indicated that strain 1ZS3-15T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus oryzisoli sp. nov. is proposed. The type strain is 1ZS3-15T (= ACCC 19783T = JCM 30487T). 相似文献
To work out a test system for studying the inhibition of isoprenoid biosynthesis through non-mevalonate pathway, the conversion
of 2-14C-methylerythritol 2,4-cyclodiphosphate (14C-MEC) into isoprenoids of three bacteria species and into plastids of 11 higher plant species was studied. The highest efficiency
(up to 63%) of the process was observed with chromoplasts from narcissus (Narcissus pseudonarcissus L.) and celandine (Chelidonium majus L.). Twenty five percent of added 14C-MEC was recovered in an isoprenoid fraction of red pepper (Capsicum annuum L.) chromoplasts. Thus, these three models can be used to test antibiotic inhibitors of isoprenoid biosynthesis. 相似文献
Human uracil N-glycosylase isoform 2—UNG2 consists of an N-terminal intrinsically disordered regulatory domain (UNG2 residues 1–92, 9.3 kDa) and a C-terminal structured catalytic domain (UNG2 residues 93–313, 25.1 kDa). Here, we report the backbone 1H, 13C, and 15N chemical shift assignment as well as secondary structure analysis of the N-and C-terminal domains of UNG2 representing the full-length UNG2 protein. 相似文献
Starch is one of the most abundant organic polysaccharides available for the production of bio-ethanol as an alternative transport fuel. Cost-effective utilisation of starch requires consolidated bioprocessing (CBP) where a single microorganism can produce the enzymes required for hydrolysis of starch, and also convert the glucose monomers to ethanol.
Results
The Aspergillus tubingensis T8.4 α-amylase (amyA) and glucoamylase (glaA) genes were cloned and expressed in the laboratory strain Saccharomyces cerevisiae Y294 and the semi-industrial strain, S. cerevisiae Mnuα1. The recombinant AmyA and GlaA displayed protein sizes of 110–150 kDa and 90 kDa, respectively, suggesting significant glycosylation in S. cerevisiae. The Mnuα1[AmyA-GlaA] and Y294[AmyA-GlaA] strains were able to utilise 20 g l-1 raw corn starch as sole carbohydrate source, with ethanol titers of 9.03 and 6.67 g l-1 (0.038 and 0.028 g l-1 h-1), respectively, after 10 days. With a substrate load of 200 g l-1 raw corn starch, Mnuα1[AmyA-GlaA] yielded 70.07 g l-1 ethanol (0.58 g l-1 h-1) after 120 h of fermentation, whereas Y294[AmyA-GlaA] was less efficient at 43.33 g l-1 ethanol (0.36 g l-1 h-1).
Conclusions
In a semi-industrial amylolytic S. cerevisiae strain expressing the A. tubingensis α-amylase and glucoamylase genes, 200 g l-1 raw starch was completely hydrolysed (saccharified) in 120 hours with 74% converted to released sugars plus fermentation products and the remainder presumably to biomass. The single-step conversion of raw starch represents significant progress towards the realisation of CBP without the need for any heat pretreatment. Furthermore, the amylases were produced and secreted by the host strain, thus circumventing the need for exogenous amylases.
For recombinant production of squalene, which is a triterpenoid compound with increasing industrial applications, in microorganisms generally recognized as safe, we screened Saccharomyces cerevisiae strains to determine their suitability. A strong strain dependence was observed in squalene productivity among Saccharomyces cerevisiae strains upon overexpression of genes important for isoprenoid biosynthesis. In particular, a high level of squalene production (400 ± 45 mg/L) was obtained in shake flasks with the Y2805 strain overexpressing genes encoding a bacterial farnesyl diphosphate synthase (ispA) and a truncated form of hydroxyl-3-methylglutaryl-CoA reductase (tHMG1). Partial inhibition of squalene epoxidase by terbinafine further increased squalene production by up to 1.9-fold (756 ± 36 mg/L). Furthermore, squalene production of 2011 ± 75 or 1026 ± 37 mg/L was obtained from 5-L fed-batch fermentations in the presence or absence of terbinafine supplementation, respectively. These results suggest that the Y2805 strain has potential as a new alternative source of squalene production. 相似文献
Two barley cultivars (Hordeum vulgare L., cvs. Elo and Belogorskii) differing in salt tolerance were used to study 22Na+ uptake, expression of three isoforms of the Na+/H+ antiporter HvNHX1-3, and the cellular localization of these isoforms in the elongation zone of seedling roots. During short
(1 h) incubation, seedling roots of both cultivars accumulated approximately equal quantities of 22Na+. However, after 24-h incubation the content of 22Na+ in roots of a salt-tolerant variety Elo was 40% lower than in roots of the susceptible variety Belogorskii. The content of
22Na+ accumulated in shoots of cv. Elo after 24-h incubation was 6.5 times lower than in shoots of cv. Belogorskii and it was 4
times lower after the salt stress treatment. The cytochemical examination revealed that three proteins HvNHX1-3 are co-localized
in the same cells of almost all root tissues; these proteins were present in the tonoplast and prevacuolar vesicles. Western
blot analysis of HvNHX1-3 has shown that the content of isoforms in vacuolar membranes increased in response to salt stress
in seedling roots and shoots of both cultivars, although the increase was more pronounced in the tolerant cultivar. The content
of HvNHX1 in the seedlings increased in parallel with the enhanced expression of HvNHX1, whereas the increase in HvNHX2 and HvNHX3 protein content was accompanied by only slight changes in expression of respective
genes. The results provide evidence that salt tolerance of barley depends on plant ability to restrict Na+ transport from the root to the shoot and relies on regulatory pathways of HvNHX1-3 expression in roots and shoots during
salt stress. 相似文献
Supplementation with CaCl2·2H2O (50 mg l−1) or CuSO4·5H2O (10 mg l−1) improved mannitol production by Candida magnoliae by 14.5 and 18.6% (25 and 32 g/L), respectively. When used in combination, they acted synergistically: Ca2+ decreased the intracellular concentration of mannitol 30%, whereas Cu2+ increased the intracellular activity of mannitol dehydrogenase 1.6-times more than control. Ca2+ probably works by altering the permeability of cells to mannitol, whereas, Cu2+ increases the activity of an enzyme responsible for mannitol biosynthesis. 相似文献
To improve cellulase production and activity, Trichoderma viride GSICC 62010 was subjected to mutation involving irradiation with an electron beam and subsequently with a 12C6+-ion beam.
Results
Mutant CIT 626 was the most promising cellulase producer after preliminary and secondary screening. Soluble protein production and cellulase activities were increased mutifold. The optimum temperature, pH and culture time for the maximum cellulase production of the selected mutant were 35 °C, pH 5 and 6 days. The highest cellulase production was obtained using wheat bran. The prepared cellulases from T. viride CIT 626 had twice the hydrolytic performance with sawdust (83 %) than that from the parent strain (42.5 %). Furthermore, molecular studies demonstrated that there were some key mutation sites suggesting that some amino acid changes in the protein caused by base mutations had led to the enhanced cellulase production and activity.
Conclusions
Mutagenesis with electron and 12C6+-ion beams could be developed as an effective tool for improvement of cellulase producing strains.