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61.
The Olifants River, a tributary of the Limpopo River system, is one of the most polluted rivers in South Africa. In May 2011 the concentrations of metals in fish muscle tissue from two impoundments, Loskop and Flag Boshielo dams, on the Olifants River were measured and a human health risk assessment conducted to investigate whether it was safe to consume Labeo rosae from these impoundments. Labeo rosae is one of the most common pan fish in these impoundments and is readily available to rural communities. Metals are accumulating in the muscle tissue of L. rosae even although the fish populations appear to be healthy. At Loskop Dam all L. rosae analysed exceeded the recommended hazard quotient (HQ) of 1 for antimony, and less than 50% exceeded that for lead. At Flag Boshielo Dam, the recommended HQ was exceeded for lead in less than 50% of L. rosae analysed, and more than 50% exceeded that for antimony. The weekly consumption of 150?g of L. rosae muscle tissue from these impoundments may pose an unacceptable health risk to rural communities. 相似文献
62.
M L Bermingham S C Bishop J A Woolliams R Pong-Wong A R Allen S H McBride J J Ryder D M Wright R A Skuce S WJ McDowell E J Glass 《Heredity》2014,112(5):543-551
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of
livestock that is of major economic importance worldwide, as well as being a zoonotic
risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy
cattle. To identify resistance loci for bTB, we undertook a genome-wide association study
in female Holstein–Friesian cattle with 592 cases and 559 age-matched controls from
case herds. Cases and controls were categorised into distinct phenotypes: skin test and
lesion positive vs skin test negative on multiple occasions, respectively. These animals
were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association
using linear and logistic mixed models and regression (GRAMMAR), regional heritability
mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that
attained chromosome-wise significance, protein tyrosine phosphatase receptor T
(PTPRT; P=4.8 × 10−7) and myosin
IIIB (MYO3B; P=5.4 × 10−6). We estimated
that 21% of the phenotypic variance in TB resistance could be explained by all of
the informative single-nucleotide polymorphisms, of which the region encompassing the
PTPRT gene accounted for 6.2% of the variance and a further 3.6%
was associated with a putative copy number variant in MYO3B. The results from
this study add to our understanding of variation in host control of infection and suggest
that genetic marker-based selection for resistance to bTB has the potential to make a
significant contribution to bTB control. 相似文献
63.
Background
The three consensus elements at the 3' end of human introns - the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide - are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides. In many cases alternative splicing regulatory elements are located within this region.Results
We have applied a simple algorithm, based on AG dinucleotide exclusion zones (AGEZ), to a large data set of verified human exons. We found a substantial number of exons with large AGEZs, which represent candidate dBP exons. We verified the importance of the predicted dBPs for splicing of some of these exons. This group of exons exhibits a higher than average prevalence of observed alternative splicing, and many of the exons are in genes with some human disease association.Conclusion
The group of identified probable dBP exons are interesting first because they are likely to be alternatively spliced. Second, they are expected to be vulnerable to mutations within the entire extended AGEZ. Disruption of splicing of such exons, for example by mutations that lead to insertion of a new AG dinucleotide between the dBP and 3' splice site, could be readily understood even though the causative mutation might be remote from the conventional locations of splice site sequences. 相似文献64.
Kim D Baas Maarten WJ Koeter Henk C van Weert Peter Lucassen Claudi LH Bockting Karin A Wittkampf Aart H Schene 《Trials》2010,11(1):1-6
Background
Previous studies of acupuncture show favourable results for both subjective and objective outcomes of dry eye. However, firm conclusions could not be drawn from these studies because the quality of the trials was too low to establish concrete evidence. Therefore, this study was designed both to avoid the flaws of the existing trials and to assess the effectiveness, cost-effectiveness and qualitative characteristics of acupuncture treatment for dry eye.Methods/design
One hundred fifty participants with dry eye will be recruited into three independent hospitals from different areas: Korea Institute of Oriental Medicine, DongGuk University Ilsan Oriental Hospital and Dongshin University Gwangju Oriental Hospital. The number of participants required was calculated from the data of a previous, relevant study. These patients will be randomly allocated into acupuncture treatment or artificial tear groups. Either 17 acupuncture points (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) will be used 3 times a week or disposable artificial tear drops (Refresh Plus®, ALLERGAN) will be provided for use at least once a day for 4 weeks. The ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer I test, visual analogue scale (VAS) for self-assessment of ocular discomfort, general assessment (by both acupuncture practitioners and participants) and quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2 (MYMOP-2) will be assessed for approximately 3-months for each study participant. In addition, qualitative study and cost-effectiveness of acupuncture treatment will be conducted.Trial registration
ClinicalTrials.gov (Identifier: NCT01105221). 相似文献65.
Audrey Leprince Mark WJ van Passel Vitor AP Martins dos Santos 《Current opinion in biotechnology》2012,23(5):651-658
Highlights? Top-down and bottom-up approaches to genome streamlining. ? Computational support for constructing and refactoring streamlined genomes. ? From genome engineering to metabolic reprogramming. ? Perspectives in applied genome engineering. 相似文献
66.
Rogier AM Quax Jan W Koper Pascal HP de Jong Ramona van Heerebeek Angelique E Weel Anne M Huisman Derkjen van Zeben Frank H de Jong Steven WJ Lamberts Johanna MW Hazes Richard A Feelders 《Arthritis research & therapy》2012,14(4):R195
Introduction
Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.Methods
Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.Results
GR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD.Conclusions
Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA. 相似文献67.
Diahann TSL Jansen Hanane el Bannoudi Ramon Arens Kim LL Habets Marjolijn Hameetman Tom WJ Huizinga Jeroen N. Stoop René EM Toes 《Arthritis research & therapy》2015,17(1)
IntroductionAbatacept is a fusion protein of human cytotoxic T-lymphocyte–associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1). It is believed to be effective in the treatment of rheumatoid arthritis by inhibiting costimulation of T cells via blocking CD28–B7 interactions as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 molecules is crucial for activation of naive cells, whereas it is unclear whether the action of already activated CD4+ T cells, which are readily present in established disease, also depends on this interaction. The aim of this study was to determine whether the mode of action of abatacept depends solely on its ability to halt T cell activation in established disease.MethodsArthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4+ T cells. Abatacept or control treatment was started when 80 % of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws, and anti-collagen antibody levels over time were determined by enzyme-linked immunosorbent assay.ResultsTreatment with abatacept in the absence of CD4+ T cells resulted in lower disease activity. This was associated with decreasing levels of collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in control or CD4+ T cell–depleted mice increased over time.ConclusionsThese results show that abatacept decreased disease activity in the absence of CD4+ T cells, indicating that the mode of action of abatacept in established arthritis does not depend entirely on its effects on CD4+ T cell activation. 相似文献
68.
Global concerns about climate changes and their association with the use of fossil fuels have accelerated research on biological
fuel production. Biological hydrogen production from hemicellulose-containing waste is considered one of the promising avenues.
A major economical issue for such a process, however, is the low substrate conversion efficiency. Interestingly, the extreme
thermophilic bacterium Caldicellulosiruptor saccharolyticus can produce hydrogen from carbohydrate-rich substrates at yields close to the theoretical maximum of the dark fermentation
process (i.e., 4 mol H2/mol hexose). The organism is able to ferment an array of mono-, di- and polysaccharides, and is relatively tolerant to high
partial hydrogen pressures, making it a promising candidate for exploitation in a biohydrogen process. The behaviour of this
Gram-positive bacterium bears all hallmarks of being adapted to an environment sparse in free sugars, which is further reflected
in its low volumetric hydrogen productivity and low osmotolerance. These two properties need to be improved by at least a
factor of 10 and 5, respectively, for a cost-effective industrial process. In this review, the physiological characteristics
of C. saccharolyticus are analyzed in view of the requirements for an efficient hydrogen cell factory. A special emphasis is put on the tight regulation
of hydrogen production in C. saccharolyticus by both redox and energy metabolism. Suggestions for strategies to overcome the current challenges facing the potential use
of the organism in hydrogen production are also discussed. 相似文献
69.
TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells 总被引:3,自引:0,他引:3
Poehlein CH Hu HM Yamada J Assmann I Alvord WG Urba WJ Fox BA 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(4):2004-2013
We have recently shown that effector T cells (T(E)) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, T(E) deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T(E) mediated complete tumor regression and cured wild-type animals with established pulmonary metastases of the B16BL6-D5 (D5) melanoma cell line. PKO/GKO T(E) also mediated tumor regression in D5 tumor-bearing PKO, GKO, or PKO/GKO recipients, although in PKO/GKO recipients efficacy was reduced. PKO/GKO T(E) exhibited tumor-specific TNF-alpha production and cytotoxicity in a 24-h assay, which was blocked by the soluble TNFRII-human IgG fusion protein (TNFRII:Fc). Blocking TNF in vivo by administering soluble TNFR II fusion protein (TNFRII:Fc) significantly reduced the therapeutic efficacy of PKO/GKO, but not wild-type T(E). This study identifies perforin, IFN-gamma, and TNF as a critical triad of effector molecules that characterize therapeutic antitumor T cells. These insights could be used to monitor and potentially tune the immune response to cancer vaccines. 相似文献
70.
Elżbieta Czarniewska Arkadiusz Urbański Szymon Chowański Mariola Kuczer 《Insect Science》2018,25(3):429-438
The subject of this article is a search for the long‐term immunological effects of alloferon and 3 structural analogues of alloferon, which were earlier characterized by the highest pro‐apoptotic activity in Tenebrio molitor. The differences in the actions of these peptides on immune response were observed. Alloferon increased nodulation and significantly phenoloxidase activity in the hemolymph of experimentally infected T. molitor. However, [Phe(p‐NH2)1]‐ and [Phe(p‐OMe)1]‐alloferon strongly inhibited cellular and humoral defense of the mealworm against Staphylococcus aureus infection. One day after injection of these peptides, the specific biochemical and morphological hallmarks of apoptosis in bacteria‐challenged hemocytes were visible; in contrast, 3 days after peptides injection in all hemocytes, caspase activation was not observed. However, these new, circulating hemocytes differed from the control and the peptide‐untreated bacteria‐challenged hemocytes. They had an increased adhesion that led to a separation of viable, anucleated fragments of hemocytes that retain the ability to adhere and to form long filopodia. The peptide‐induced separation of hemocyte fragments may resemble the formation of platelets in mammals and perhaps play a role in sealing wounds in insects. The results of in vivo studies may suggest a long half‐life of studied peptides in the hemolymph of mealworm. Moreover, we showed the importance of the N‐terminal histidine residues at position one of the alloferon molecule for its immunological properties in insects. The results obtained here show that alloferon plays pleiotropic functions in insects. 相似文献