Characterization and virulence of hemolysin III from Vibrio vulnificus

Vibrio vulnificus, a highly virulent marine bacterium, is the causative agent of both serious wound infections and fatal septicemia in many areas of the word. A gene (hlyIII) encoding a hemolysin was cloned and sequenced from V. vulnificus. Nucleotide sequence analysis predicted an open reading frame of 642 bp encoding a 214 amino acid polypeptide that showed 48% sequence identity to the hemolysin III of Bacillus cereus. When HlyIII of V. vulnificus was expressed in Escherichia coli, crude extracts exhibited hemolytic activity similar to that of hemolysin III from Bacillus cereus. A hlyIII isogenic mutant was constructed via insertional inactivation and showed an attenuated virulence compared with the wild-type strain when this mutant was administered intraperitoneally in mice

Using system simulation to search for the optimal multi-ordering policy for perishable goods

[EN] This paper explores the possibility that perishable goods can be ordered several times in a single period after considering the cost of Marginal contribution, Marginal loss, Shortage, and Purchasing under stochastic demand. In order to determine the optimal ordering quantity to improve the traditional newsvendor and maximize the total expected profits, and then sensitivity analysis is taken to realize the influence of the parameters on total expected profits and decision variables respectively. In addition, this paper designed a multi-order computerized system with Monte Carlo method to solve the optimal solution under stochastic demand. Based on numerical examples, this paper verified the feasibility and efficiency of the proposed model. Finally, several specific conclusions are drawn for practical applications and future studies.Huang, Y.; Chang, X.; Ding, Y. (2019). Using system simulation to search for the optimal multi-ordering policy for perishable goods. International Journal of Production Management and Engineering. 7(1):49-62. https://doi.org/10.4995/ijpme.2019.10745SWORD496271Azoury, K.S., Miller, B.L. (1984). A comparison of the optimal ordering levels of bayesian and non-bayesian inventory models, Management Science, 30(8), 993-1003. https://doi.org/10.1287/mnsc.30.8.993Alfares, H.K., Elmorra, H.H. (2005). The distribution-free newsboy problem: extensions to the shortage penalty case, International Journal of Production Economics, 93-94(8), 465-477. https://doi.org/10.1016/j.ijpe.2004.06.043Chung, C.S., Flynn, J. (2001). A newsboy problem with reactive production, Computers & Operations Research, 28(8), 751-765. https://doi.org/10.1016/S0305-0548(00)00006-XChun, Y.H. (2003). Optimal pricing and ordering policies for perishable commodities, European Journal of Operational Research, 144(1), 68-82. https://doi.org/10.1016/S0377-2217(01)00351-4Chen, L.H., Chen, Y.C. (2009). A newsboy problem with a simple reservation arrangement. Computers & Industrial Engineering, 56(1), 157-160. https://doi.org/10.1016/j.cie.2008.04.010Dian, J.R. (1990). A high-low search algorithm for a newsboy problem with delayed information feedback. Operations Research, 38(5), 838-846. https://doi.org/10.1287/opre.38.5.838Dye, C.Y., Ouyang, L.Y. (2005). An EOQ model for perishable items under stock-dependent selling rate and time-dependent partial backlogging. European Journal of Operational Research, 163(3), 776-783. https://doi.org/10.1016/j.ejor.2003.09.027Fujiwara, O., Soewandi, H., Sedarage, D. (1997). An optimal ordering and issuing policy for a two-stage inventory system for perishable products. European Journal of Operational Research, 99(2), 412-424. https://doi.org/10.1016/S0377-2217(95)00365-7Gallego, G., Moon, I. (1993). The distribution free newsboy problem: review and extensions. Journal of the Operational Research Society, 44(8), 825-834. https://doi.org/10.1057/jors.1993.141Khouja, M. (1999). The single-period (news-vendor) problem: literature review and suggestions for future research. Omega, 27(5), 537-553. https://doi.org/10.1016/S0305-0483(99)00017-1Khouja, M.J. (2000). Optimal ordering, discounting, and pricing in the single-period problem. International Journal of Production Economics, 65(2), 201-216. https://doi.org/10.1016/S0925-5273(99)00027-4Lau, H., Lau, H. (1998). Decision models for single-period products with two ordering opportunities. International Journal of Production Economics, 55(1), 57-70. https://doi.org/10.1016/S0925-5273(98)00040-1Padmanabhan, G., Vrat, P. (1995). EOQ models for perishable items under stock dependent selling rate. European Journal of Operational Research, 86(2), 281-292. https://doi.org/10.1016/0377-2217(94)00103-JPando, V., Luis, A.S.J., Juan, G.L., Sicilia, J. (2013). A newsboy problem with an emergency order under a general backorder rate function. Omega, 41(6), 1020-1028. https://doi.org/10.1016/j.omega.2013.01.003Zheng, M., Wu, K., Shu, Y. (2016). Newsvendor problems with demand forecast updating and supply constraints. Computers & Operations Research, 67, 193-206. https://doi.org/10.1016/j.cor.2015.10.00

Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription

CEBPB, one of the CEBP family members, is a crucial regulator of gene expression during innate immunity, inflammatory responses and adipogenesis. In this study, the EGF-induced increase of CEBPB mRNA is shown to be coincident with the decrease of COX-2 mRNA. We identified that all of the individual CEBPB isoforms, LAP1, LAP2 and LIP, attenuate EGF-induced COX-2 promoter activity. Although increased sumoylation of both LAP1 and LAP2 is observed during the lagging stage of EGF treatment, only the sumoylated LAP1, but not the sumoylated LAP2, is responsible for COX-2 gene repression. In addition, EGF treatment can regulate the nucleocytoplasmic redistribution of HDAC4 and SUMO1. We further demonstrated by loss-of- and gain-of-function approaches that HDAC4 can be a negative regulator while inactivating COX-2 transcription. The sumoylation mutant LAP1, LAP1K174A, exhibits an attenuated ability to interact with HDAC4, and increased COX-2 promoter activity. Furthermore, the in vivo DNA binding assay demonstrated that LAP1K174A and CEBPDK120A, sumoylation-defective CEBPD mutants, attenuate the binding of HDAC4 on the COX-2 promoter. In light of the above, our data suggest that the suCEBPD and suLAP1 are involved in the repression of COX-2 transcription through the recruitment of HDAC4

A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM. 23 females with LAM were randomised to doxycycline 100 mg daily for 3 months followed by 200 mg daily for 21 months, or matched placebo. Lung function, exercise capacity, quality of life and matrix metalloproteinases levels were measured. 21 patients completed 6 months of treatment, 17 completed 1 year of treatment and 15 completed 2 years of treatment. Eight withdrew from the trial due, four due to a pneumothorax and four because of other reasons. The mean±sd decline in FEV1, the primary endpoint, did not differ between the groups being -90±154 mL·year−1 in the placebo group and -123±246 mL·year−1 in the doxycycline group (difference -32.5, 95% CI -213–148; p=0.35). Doxycycline had no effect upon vital capacity, gas transfer, shuttle walk distance or quality of life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline treatment (p=0.03). Although with limited numbers we cannot completely exclude an effect of doxycycline, the lack of effect on any outcome makes it unlikely that doxycycline has a useful effect in LAM

Baculovirus Transduction of Mesenchymal Stem Cells: In Vitro Responses and In Vivo Immune Responses After Cell Transplantation

Baculovirus holds great promise for the genetic modification of mesenchymal stem cells (MSCs). However, whether baculovirus transduction provokes undesired MSCs responses that might compromise their in vivo applications has yet to be examined. Hereby, we unraveled that baculovirus transduction of human MSCs upregulated the transcription of interleukin (IL)-1 beta, interferon (IFN)-alpha and IL-6, but not tumor necrosis factor (TNF)-alpha and IFN-gamma. However, only IL-6 secretion was detectable by enzyme-linked immunosorbent assay (ELISA). Baculovirus transduction also stimulated transient, low level upregulation of human leukocyte antigen I (HLA-I) on the human MSCs surface, yet it did not either altered the HLA-II expression or impaired the MSCs ability to inhibit lymphocyte proliferation. After transplantation into allogeneic rats, the transduced rat MSCs elicited transient, mild macrophage responses, but the cells remained tolerant as judged by the persistence of transplanted cells and absence of CD8(+) T cells infiltration. Besides, transplantation of the transduced MSCs did not provoke systemic induction of monocytes and CD8(+) T cells. This study, for the first time, explores the responses of MSCs to virus transduction and confirms the safety of transplanting baculovirus-engineered MSCs into immunocompetent animals for cell-based gene therapy

Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3

<p>Abstract</p> <p>Background</p> <p>Although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of DENV-3. In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed.</p> <p>Results</p> <p>Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan's indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes – I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Sequence diversity and selection pressure of different genomic regions among DENV-3 different genotypes was further examined to understand the global DENV-3 evolution. The highest nucleotide sequence diversity among the fully sequenced DENV-3 strains was found in the nonstructural protein 2A (mean ± SD: 5.84 ± 0.54) and envelope protein gene regions (mean ± SD: 5.04 ± 0.32). Further analysis found that positive selection pressure of DENV-3 may occur in the non-structural protein 1 gene region and the positive selection site was detected at position 178 of the NS1 gene.</p> <p>Conclusion</p> <p>Our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. The detection of positive selection pressure in the non-structural protein along genotype II indicated that DENV-3 originated from Southeast Asia needs to monitor the emergence of DENV strains with epidemic potential for better epidemic prevention and vaccine development.</p

Identifying a Universal Activity Descriptor and a Unifying Mechanism Concept on Perovskite Oxides for Green Hydrogen Production

Producing indispensable hydrogen and oxygen for social development via water electrolysis shows more prospects than other technologies. Although electrocatalysts have been explored for centuries, a universal activity descriptor for both hydrogen-evolution reaction (HER) and oxygen-evolution reaction (OER) is not yet developed. Moreover, a unifying concept is not yet established to simultaneously understand HER/OER mechanisms. Here, the relationships between HER/OER activities in three common electrolytes and over ten representative material properties on 12 3d-metal-based model oxides are rationally bridged through statistical methodologies. The orbital charge-transfer energy (Δ) can serve as an ideal universal descriptor, where a neither too large nor too small Δ (≈1 eV) with optimal electron-cloud density around Fermi level affords the best activities, fulfilling Sabatier's principle. Systematic experiments and computations unravel that pristine oxide with Δ ≈ 1 eV possesses metal-like high-valence configurations and active lattice-oxygen sites to help adsorb key protons in HER and induce lattice-oxygen participation in the OER, respectively. After reactions, partially generated metals in the HER and high-valence hydroxides in the OER dominate proton adsorption and couple with pristine lattice-oxygen activation, respectively. These can be successfully rationalized by the unifying orbital charge-transfer theory. This work provides the foundation of rational material design and mechanism understanding for many potential applications