Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that can recognize pathogen-associated molecular patterns (PMPs) and play important roles in the innate immune system in vertebrates. In t...
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Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that can recognize pathogen-associated molecular patterns (PMPs) and play important roles in the innate immune system in vertebrates. In this study, we identified a teleost-specific tlr22 gene from yellow catfish (Pelteobagrus fulvidraco) and its immune roles in response to different pathogens were also determined. The open reading frame (ORF) of the tlr22 was 2892 bp in length, encoding a protein of 963 amino acids. Multiple protein sequences alignment, secondary and three-dimensional structure analyses revealed that TLR22 is highly conserved among different fish species. Phylogenetic analysis showed that the phylogenetic topology was divided into six families of TLR1, TLR3, TLR4, TLR5, TLR7 and TLR11, and TLR22 subfamily was clustered into TLR11 family. Meanwhile, synteny and gene structure comparisons revealed functional and evolutionary conservation of the tlr22 gene in teleosts. Further-more, tlr22 gene was shown to be widely expressed in detected tissues except barbel and eye, with highest expression level in liver. The transcription of tlr22 was significantly increased in spleen, kidney, liver and gill tissues at different timepoints after Poly I:c infection, suggesting TLR22 plays critical roles in defensing virus invasion. Similarly, the transcription of tlr22 was also dramatically up-regulated in spleen, kidney and gill tissues with different patterns after Aeromonas hydrophila infection, indicating that TLR22 is also involved in resisting bacteria invasion. Our findings will provide a solid basis for the investigation the immune functions of tlr22 gene in teleosts, as well as provide useful information for disease control and treatment for yellow catfish.
A simple methodology has been developed for the synthesis of previously unstudied N-substituted glutarimide derivatives - (Z)-1-(aryl(arylimino)methyl)piperidine-2,6-diones 4 a-p obtained in one step from c,N-diarylfo...
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A simple methodology has been developed for the synthesis of previously unstudied N-substituted glutarimide derivatives - (Z)-1-(aryl(arylimino)methyl)piperidine-2,6-diones 4 a-p obtained in one step from c,N-diarylformamidines 1 a-p and glutaric anhydride 6 with product yields from 46 up to 88 % and chromatographic purity from 94 to 99 %. The structures of the obtained compounds were proved using NMR spectroscopy H-1, c-13, X-ray diffraction analysis, mass spectroscopy, and elemental analysis. An in vivo study of the analgesic activity of a representative of series 4 a was carried out.
Genetic variations in the AGT gene play a significant role in controlling the plasma concentration of angiotensinogen (precursor protein of bioactive octapeptide angiotensin II) and the efficacy of antihypertensive dr...
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Genetic variations in the AGT gene play a significant role in controlling the plasma concentration of angiotensinogen (precursor protein of bioactive octapeptide angiotensin II) and the efficacy of antihypertensive drugs. In the current study, Tetra-Amplification Refractory Mutation System-Polymerase chain Reaction (T-ARMS-PcR) was developed for genotyping of AGT rs699 T/c polymorphism and validated through Sanger DNA sequencing. Its efficiency was also tested using 474 human DNA samples [control, n = 181;cardiovascular disease (cVD) patients, n = 293]. Results showed that T-ARMS-PcR is superior to the commonly used PcR-Restriction Fragment Length Polymorphism (PcR-RFLP). Statistical analysis revealed that the AGT rs699 cc genotype is more prevalent in the cVD patient group (37% vs. 28%) and AGT rs699 c allele and cc genotype increased the risk of cVD by 1.4 and 1.9 fold, respectively. In summary, T-ARMS-PcR is the most suitable approach for quick and efficient genotyping of AGT rs699 T/c polymorphism in a large population in resource-limited countries, Furthermore, AGT rs699 T/c polymorphism is associated with the risk of cVD in the Punjabi Pakistani population.
This paper presents a prioritisation procedure to rank reinforced concrete (r.c.) buildings that are part of a stock according to their seismic vulnerability, and to plan further verifications and retrofit interventio...
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This paper presents a prioritisation procedure to rank reinforced concrete (r.c.) buildings that are part of a stock according to their seismic vulnerability, and to plan further verifications and retrofit interventions. The proposed approach is based on visual inspections, qualitative evalua-tion, and quantitative assessment. The qualitative evaluation is based on a new deficiency form, here presented, whereas the quantitative assessment is carried out through a simplified me-chanical model, which provides a ratio of capacity to demand. This work thus proposes a com-bination of the qualitative and quantitative approaches aimed at prioritisation. In this way, specific limitations of each approach are overcome through the combination. The proposed procedure was applied to the r.c. school building asset managed by the municipality of Padova (Italy). After describing the main characteristics of the inspected stock, the paper discusses the most commonly observed vulnerability factors and the application of the procedure. The quali-tative and quantitative approaches integrated each other quite well and showed a general good agreement.
Understanding how we can age healthily is a challenge at the heart of biogerontological interest. Whereas myriad genes are known to affect the lifespan of model organisms, effects of such interventions on healthspan-t...
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Understanding how we can age healthily is a challenge at the heart of biogerontological interest. Whereas myriad genes are known to affect the lifespan of model organisms, effects of such interventions on healthspan-the period of life where an animal is considered healthy, rather than merely alive-are less clear. To understand relationships between life- and healthspan, in recent years several platforms were developed with the purpose of assessing both readouts simultaneously. We here relied on one such platform, the WorMotel, to study effects of adulthood-restricted knock-down of 130 caenorhabditis elegans genes on the locomotive health of the animals along their lifespans. We found that knock-down of six genes affected healthspan while lifespan remained unchanged. For two of these, F26A3.4 and chn-1, knock-down resulted in an improvement of healthspan. In follow-up experiments we showed that knockdown of F26A3.4 indeed improves locomotive health and muscle structure at old age.
In decapod crustaceans, the conditions experienced during embryonic development trigger phenotypic plasticity of the larvae at hatching. The objective of this study was to test the effects of temperature during embryo...
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In decapod crustaceans, the conditions experienced during embryonic development trigger phenotypic plasticity of the larvae at hatching. The objective of this study was to test the effects of temperature during embryonic development of Palaemon serratus on the phenotypic plasticity of hatching larvae. We incubated egg-bearing females from eggs laying to hatching at four temperatures (10, 15, 18 and 20 degrees c). Weight, carbon and nitrogen contents were measured on newly laid eggs and on freshly hatched larvae. The duration of embryonic development was negatively correlated with incubation temperature. At 20 degrees c, all females abandoned their eggs during development. Incubation temperature had no effect on the weight and the percentage of N of the larvae at hatching, while it did affect their percentage of c and their c/N ratio. Embryos incubated at 10 degrees c seemed to produce larvae with fewer lipid reserves than those incubated at 15 and 18 degrees c. They probably overconsumed their lipid reserves to compensate for the metabolic losses due to the low temperature. These results provide information on the link between maternal investment per egg and larval development in P. serratus.
The Rust language was created to provide safe low-level systems programming. There is both industrial and academic interest in the problem of (semi-)automatically translating ccode to Rust in order to exploit Rust...
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The Rust language was created to provide safe low-level systems programming. There is both industrial and academic interest in the problem of (semi-)automatically translating ccode to Rust in order to exploit Rust's safety guarantees. We study the effectiveness and limitations of existing techniques for automatically translating unsafe raw pointers (in Rust programs translated from c) into safe Rust references via ownership and lifetime inference. Our novel evaluation methodology enables our study to extend beyond prior studies, and to discover new information contradicting the conclusions of prior studies. We find that existing translation methods are severely limited by a lack of precision in the Rust compiler's safety checker, causing many safe pointer manipulations to be labeled as potentially unsafe. Leveraging this information, we propose methods for improving translation, based on encoding the results of a more precise analysis in a manner that is understandable to an unmodified Rust compiler. We implement one of our proposed methods, increasing the number of pointers that can be translated to safe Rust references by 75% over the baseline (from 12% to 21% of all pointers).
Intestinal bile acids play an essential role in the clostridioides difficile lifecycle having been shown in vitro to modulate various aspects of pathogenesis, including spore germination, vegetative growth, and more r...
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Intestinal bile acids play an essential role in the clostridioides difficile lifecycle having been shown in vitro to modulate various aspects of pathogenesis, including spore germination, vegetative growth, and more recently the action of the primary virulence determinant, TcdB. Here, we investigated whether physiological levels of the total pool of intestinal bile acids in mice and humans protect against TcdB action. Small molecules extracted from the lumenal contents of the small intestine, cecum, colon, and feces were found to inhibit TcdB in accordance with the differential amounts of total bile acids in each compartment. Extracts from antibiotic-treated and germ-free mice, despite harboring dramatically altered bile acid profiles, unexpectedly also prevented TcdB-induced cell rounding to similar extents. We show that protection, however, is surmountable and can be overcome at higher doses of TcdB-typical to those seen during severe c. difficile infection-suggesting that the protective properties of intestinal bile acids are operant primarily under low to moderate toxin levels. Taken together, these findings demonstrate a role for intestinal bile acids in attenuating virulence, provide insights into asymptomaticcarriage of toxigenicc. difficile, and inform strategies to manipulate bile acid levels for therapeutic benefit.
Using zinc nitrate hexahydrate and 2-methylimidazole as raw materials, ZIF-8 was successfully prepared in the methanol solvent. Through the stepwise strategies of pyrolysis and calcination at different temperatures an...
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Using zinc nitrate hexahydrate and 2-methylimidazole as raw materials, ZIF-8 was successfully prepared in the methanol solvent. Through the stepwise strategies of pyrolysis and calcination at different temperatures and atmospheres, the desired product of ZnO/ccomposite was obtained. The techniques of XRD, FT-IR and SEM were used to determine the structure and morphology of samples, respectively. The results showed that ZnO/ccomposite retained the hexagonal polyhedron morphology of ZIF-8 and constructed a porous structure. And, the photocatalytic degradation of methylene blue solution was carried out using ZnO/c and referenced ZnO as catalysts, respectively. The results declared that the improved catalytic property of ZnO/ccomposite benefited from the synergistic effect of ZnO and porous carbon skeleton. The excellent degradation ability of ZnO/c was achieved. This work provided a facile way to develop ZnO-based photocatalysts with the desired photocatalytic performance.
Background BALB/c and c57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model. M...
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Background BALB/c and c57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model. Methods Eighteen BALB/c and eighteen c57BL/6 mice received different doses of ovalbumin (OVA) intranasally for eight weeks (each mouse strain has three subgroups, 25 mg/mL group, 0.25 mg/mL group, and the PBS group). The allergic symptoms, OVA-specific serum antibody (IgE, IgG1, IgG2a), cytokines (IL-4, IFN-gamma, IL-10) in the splenicculture supernatant, infiltrating eosinophils and goblet cells in local nasal mucosa were measured. RNA-seq technology was applied to detect differential gene expression in the local nasal mucosa. Results With the same dose of OVA stimulation, the exacerbation of allergic symptoms was more pronounced in c57BL/6 than in BALB/c. BALB/c serum IgE, IgG1, and IgG2a gradually increased, and c57BL/6 produced fewer serum antibodies IgE and IgG1, while IgG2a never increased. BALB/c spleen cell culture supernatant IL-4 and IL-10 increased with increasing dose, and IFN-gamma increased significantly in the intermediate dose group, while IL-4, IL-10, and IFN-gamma did not increase in c57BL/6. The infiltration of eosinophils and goblet cells in both mice was proportional to the dose, while c57BL/6 was elevated more than BALB/c. RNA-seq suggested that the innate immune response, immune system process function, Jun kinase (JNK) pathway, and MAPKK pathway were upregulated in c57BL/6 compared to BALB/c. The core genes responsible for the differential immune response in both mice with allergic rhinitis were Kng2, Kng1, Gnb3, Lpar3, Lpar1, Pik3r1, Pf4, Apob, Rps9, and Fbxo2. conclusion There are significant differences in the immunologic responses between BALB/c mice and c57BL/6 mice. BALB/c mice developed mild local allergic inflammatory reactions and strong systemic immune responses. In contrast, c57BL/6 mice had stronger local allergic inf
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