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21.
22.
Way SS Kollmann TR Hajjar AM Wilson CB 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(2):533-537
In addition to their role in triggering innate immune responses, Toll-like receptors are proposed to play a key role in linking the innate and adaptive arms of the immune response. The majority of cellular responses downstream of Toll-like receptors are mediated through the adapter molecule myeloid differentiation factor 88 (MyD88), and mice with a targeted deletion of MyD88 are highly susceptible to bacterial infections, including primary infection with Listeria monocytogenes (LM). In contrast, herein we demonstrate that MyD88-deficient mice have only a modest impairment in their LM-specific CD4 T cell response, and no impairment in their CD8 T cell response following infection with ActA-deficient LM. Furthermore, CD8 T cells from immunized MyD88-deficient mice protected naive recipient mice following adoptive splenocyte transfer, and immunized MyD88-deficient mice were protected from infection with wild-type LM. These results indicate that adaptive immune responses can be generated and provide protective immunity in the absence of MyD88. 相似文献
23.
Seligman LM Chisholm KM Chevalier BS Chadsey MS Edwards ST Savage JH Veillet AL 《Nucleic acids research》2002,30(17):3870-3879
The homing endonuclease I-CreI recognizes and cleaves a particular 22 bp DNA sequence. The crystal structure of I-CreI bound to homing site DNA has previously been determined, leading to a number of predictions about specific protein–DNA contacts. We test these predictions by analyzing a set of endonuclease mutants and a complementary set of homing site mutants. We find evidence that all structurally predicted I-CreI/DNA contacts contribute to DNA recognition and show that these contacts differ greatly in terms of their relative importance. We also describe the isolation of a collection of altered specificity I-CreI derivatives. The in vitro DNA-binding and cleavage properties of two such endonucleases demonstrate that our genetic approach is effective in identifying homing endonucleases that recognize and cleave novel target sequences. 相似文献
24.
Cheviron N Rousseau-Plasse A Lenfant M Adeline MT Potier P Thierry J 《Analytical biochemistry》2000,280(1):58-64
N-Acetyl-Ser-Asp-Lys-Pro-OH (AcSDKP-OH), a negative regulator of hematopoietic stem cell proliferation, is shown to be a physiological substrate of angiotensin I-converting enzyme (ACE), a zinc-dipeptidyl carboxypeptidase, involved in cardiovascular homeostasis. Recently, a study carried out on captopril-treated volunteers revealed that the kinetics of [3H]AcSDKP-OH hydrolysis in vitro in the plasma of donors correlates closely to the plasmatic ratio angiotensin II/angiotensin I, which characterized the conversion activity of ACE. This prompted us to design a fluorescent substrate, 2-[7-(dimethylamino)-2-oxo-2H-chromen-4-yl]acetyl-SDKP-OH, or coumarin-SDKP-OH, which could be an alternative to the radiolabeled analogue used in that study, allowing an easier and more rapid determination of enzyme activity. We report here the synthesis and the determination of the kinetics constants of this fluorescent derivative compared with those of [3H]AcSDKP-OH with human plasma ACE (133 and 125 microM, respectively), which are in the same range as those of the physiological substrate angiotensin I. Furthermore, the hydrolysis of the fluorescent substrate shows the same sensitivity toward chloride concentration as the natural substrate, demonstrating its specificity for N-domain hydrolysis. This fluorescent derivative was used to develop a sensitive assay for the determination of ACE activity in human plasma. 相似文献
25.
Ugo Maninchedda Olivier M. Lepage Monika Gangl Sandrine Hilairet Bernard Remandet Francoise Meot Geraldine Penarier Emilie Segard Pierre Cortez Christian Jorgensen Régis Steinberg 《PloS one》2015,10(2)
The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. 相似文献
26.
Tanya M. Smith Paul Tafforeau Adeline Le Cabec Anne Bonnin Alexandra Houssaye Joane Pouech Jacopo Moggi-Cecchi Fredrick Manthi Carol Ward Masrour Makaremi Colin G. Menter 《PloS one》2015,10(2)
Until recently, our understanding of the evolution of human growth and development derived from studies of fossil juveniles that employed extant populations for both age determination and comparison. This circular approach has led to considerable debate about the human-like and ape-like affinities of fossil hominins. Teeth are invaluable for understanding maturation as age at death can be directly assessed from dental microstructure, and dental development has been shown to correlate with life history across primates broadly. We employ non-destructive synchrotron imaging to characterize incremental development, molar emergence, and age at death in more than 20 Australopithecus anamensis, Australopithecus africanus, Paranthropus robustus and South African early Homo juveniles. Long-period line periodicities range from at least 6–12 days (possibly 5–13 days), and do not support the hypothesis that australopiths have lower mean values than extant or fossil Homo. Crown formation times of australopith and early Homo postcanine teeth fall below or at the low end of extant human values; Paranthropus robustus dentitions have the shortest formation times. Pliocene and early Pleistocene hominins show remarkable variation, and previous reports of age at death that employ a narrow range of estimated long-period line periodicities, cuspal enamel thicknesses, or initiation ages are likely to be in error. New chronological ages for SK 62 and StW 151 are several months younger than previous histological estimates, while Sts 24 is more than one year older. Extant human standards overestimate age at death in hominins predating Homo sapiens, and should not be applied to other fossil taxa. We urge caution when inferring life history as aspects of dental development in Pliocene and early Pleistocene fossils are distinct from modern humans and African apes, and recent work has challenged the predictive power of primate-wide associations between hominoid first molar emergence and certain life history variables. 相似文献
27.
Consumption and handling of chicken meat are well-known risk factors for acquiring campylobacteriosis. This study aimed to describe the Campylobacter jejuni population in Finnish chickens and to investigate the distribution of C. jejuni genotypes on Finnish chicken farms over a period of several years. We included 89.8% of the total C. jejuni population recovered in Finnish poultry during 2004, 2006, 2007, 2008, and 2012 and used multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to characterize the 380 isolates. The typing data was combined with isolate information on collection-time and farm of origin. The C. jejuni prevalence in chicken slaughter batches was low (mean 3.0%, CI95% [1.8%, 4.2%]), and approximately a quarter of Finnish chicken farms delivered at least one positive chicken batch yearly. In general, the C. jejuni population was diverse as represented by a total of 63 sequence types (ST), but certain predominant MLST lineages were identified. ST-45 clonal complex (CC) accounted for 53% of the isolates while ST-21 CC and ST-677 CC covered 11% and 9% of the isolates, respectively. Less than half of the Campylobacter positive farms (40.3%) delivered C. jejuni-contaminated batches in multiple years, but the genotypes (ST and PFGE types) generally varied from year to year. Therefore, no evidence for a persistent C. jejuni source for the colonization of Finnish chickens emerged. Finnish chicken farms are infrequently contaminated with C. jejuni compared to other European Union (EU) countries, making Finland a valuable model for further epidemiological studies of the C. jejuni in poultry flocks. 相似文献
28.
Yohanna Kamabi Avong Petros Isaakidis Sven Gudmund Hinderaker Rafael Van den Bergh Engy Ali Bolajoko Oladunni Obembe Ernest Ekong Clement Adebamowo Nicaise Ndembi James Okuma Adeline Osakwe Olanrewaju Oladimeji Gabriel Akang Joshua Olusegun Obasanya Osman Eltayeb Aderonke Vivian Agbaje Alash’le Abimiku Charles Olalekan Mensah Patrick Sunday Dakum 《PloS one》2015,10(3)
Background
Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria.Method
This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed.Results
Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28–42] and median weight was 51 kg (IQR: 45–59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1–2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs.Conclusion
Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated. 相似文献29.
Jean-Fran?ois Bastin Adeline Fayolle Yegor Tarelkin Jan Van den Bulcke Thales de Haulleville Frederic Mortier Hans Beeckman Joris Van Acker Adeline Serckx Jan Bogaert Charles De Cannière 《PloS one》2015,10(11)
Context
Wood specific gravity is a key element in tropical forest ecology. It integrates many aspects of tree mechanical properties and functioning and is an important predictor of tree biomass. Wood specific gravity varies widely among and within species and also within individual trees. Notably, contrasted patterns of radial variation of wood specific gravity have been demonstrated and related to regeneration guilds (light demanding vs. shade-bearing). However, although being repeatedly invoked as a potential source of error when estimating the biomass of trees, both intraspecific and radial variations remain little studied. In this study we characterized detailed pith-to-bark wood specific gravity profiles among contrasted species prominently contributing to the biomass of the forest, i.e., the dominant species, and we quantified the consequences of such variations on the biomass.Methods
Radial profiles of wood density at 8% moisture content were compiled for 14 dominant species in the Democratic Republic of Congo, adapting a unique 3D X-ray scanning technique at very high spatial resolution on core samples. Mean wood density estimates were validated by water displacement measurements. Wood density profiles were converted to wood specific gravity and linear mixed models were used to decompose the radial variance. Potential errors in biomass estimation were assessed by comparing the biomass estimated from the wood specific gravity measured from pith-to-bark profiles, from global repositories, and from partial information (outer wood or inner wood).Results
Wood specific gravity profiles from pith-to-bark presented positive, neutral and negative trends. Positive trends mainly characterized light-demanding species, increasing up to 1.8 g.cm-3 per meter for Piptadeniastrum africanum, and negative trends characterized shade-bearing species, decreasing up to 1 g.cm-3 per meter for Strombosia pustulata. The linear mixed model showed the greater part of wood specific gravity variance was explained by species only (45%) followed by a redundant part between species and regeneration guilds (36%). Despite substantial variation in wood specific gravity profiles among species and regeneration guilds, we found that values from the outer wood were strongly correlated to values from the whole profile, without any significant bias. In addition, we found that wood specific gravity from the DRYAD global repository may strongly differ depending on the species (up to 40% for Dialium pachyphyllum).Main Conclusion
Therefore, when estimating forest biomass in specific sites, we recommend the systematic collection of outer wood samples on dominant species. This should prevent the main errors in biomass estimations resulting from wood specific gravity and allow for the collection of new information to explore the intraspecific variation of mechanical properties of trees. 相似文献30.
Jodi L. Vanden Eng Adeline Chan Ana Paula Abílio Adam Wolkon Gabriel Ponce de Leon John Gimnig Juliette Morgan 《PloS one》2015,10(6)