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71.
Matthew R. Golden Roxanne P. Kerani Mark Stenger James P. Hughes Mark Aubin Cheryl Malinski King K. Holmes 《PLoS medicine》2015,12(1)
BackgroundExpedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women.ConclusionsA public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level.
Trial Registration
ClinicalTrials.gov NCT01665690相似文献72.
Owen C Chen F Flenniken AM Osborne LR Ichikawa S Adamson SL Rossant J Aubin JE 《Journal of cellular biochemistry》2012,113(7):2432-2441
X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disease characterized by renal phosphate wasting, aberrant vitamin D metabolism, and defective bone mineralization. It is known that XLH in humans and in certain mouse models is caused by inactivating mutations in PHEX/Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). By a genome-wide N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a dominant mouse mutation that exhibits the classic clinical manifestations of XLH, including growth retardation, skeletal abnormalities (rickets/osteomalacia), hypophosphatemia, and increased serum alkaline phosphatase (ALP) levels. Mapping and sequencing revealed that these mice carry a point mutation in exon 14 of the Phex gene that introduces a stop codon at amino acid 496 of the coding sequence (Phex(Jrt) also published as Phex(K496X) [Ichikawa et al., 2012]). Fgf23 mRNA expression as well as that of osteocalcin, bone sialoprotein, and matrix extracellular phosphoglycoprotein was upregulated in male mutant long bone, but that of sclerostin was unaffected. Although Phex mRNA is expressed in bone from mutant hemizygous male mice (Phex(Jrt)/Y mice), no Phex protein was detected in immunoblots of femoral bone protein. Stromal cultures from mutant bone marrow were indistinguishable from those of wild-type mice with respect to differentiation and mineralization. The ability of Phex(Jrt)/Y osteoblasts to mineralize and the altered expression levels of matrix proteins compared with the well-studied Hyp mice makes it a unique model with which to further explore the clinical manifestations of XLH and its link to FGF23 as well as to evaluate potential new therapeutic strategies. 相似文献
73.
François Mankessi Aubin Saya Christelle Baptiste Sophie Nourissier Olivier Monteuuis 《Trees - Structure and Function》2009,23(5):931-940
In vitro responsiveness of microshoots derived from three genetically related and different age Eucalyptus urophylla × Eucalyptus grandis clones kept cultivated by monthly subcultures was assessed on two rooting media in relation to the time spent in culture.
Significant differences of rooting capacity were found between the two 22-year-old half sibling genotypes 147 and 149 according
to the concentration of BA added to the media and also to light intensity. The contrast was even more salient with the 1-year-old
clone S, which displayed the poorest rooting ability despite being full sibling with clone 147 and much younger. The various criteria
observed, i.e. rooting rate, number of roots produced, root length, microshoot height and shoot tip necrosis varied greatly
and differently for the three origins according to the successive time replicates of the same rooting protocols, with rooting
rates of more than 80% for clone 147 at certain dates. These results were discussed, suggesting the influence of endogenous
rhythms as the most rationale cause of the time-related fluctuations of responses observed in steady in vitro environment,
notwithstanding possible interferences of non-optimal tissue culture conditions. Such unexpected variations of rootability
between closely related genotypes, and the notable interactions pointed out between the time spent in culture and the rooting
conditions deserve to be taken into consideration before stating definitive judgment on the rooting capacities of a given
genotype for arborescent species. 相似文献
74.
IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production 下载免费PDF全文
Lisa M. Maier Christopher E. Lowe Jason Cooper Kate Downes David E. Anderson Christopher Severson Pamela M. Clark Brian Healy Neil Walker Cristin Aubin Jorge R. Oksenberg Stephen L. Hauser Alistair Compston Stephen Sawcer The International Multiple Sclerosis Genetics Consortium Philip L. De Jager Linda S. Wicker John A. Todd David A. Hafler 《PLoS genetics》2009,5(1)
Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report “allelic heterogeneity” at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels. 相似文献
75.
François Mankessi Aubin R. Saya Frédéric Boudon Yann Guédon Fabienne Montes Marc Lartaud Jean-Luc Verdeil Olivier Monteuuis 《Trees - Structure and Function》2010,24(4):743-752
Shoot apical meristem (SAM) domes derived from five different outdoor and in vitro sources of juvenile and mature Eucalyptus urophylla × Eucalyptus grandis akin genotypes were compared. Overall measurements of SAM dome height H and diameter D ranged from 2 to 35 μm and 20 to 80 μm, with significant differences according to the various physiological origins of plant
material investigated. SAM domes from the mature trees “Mat” were taller than those from the rejuvenated ministock plants
“Rej”; from the in vitro microcuttings “IVM” of the same clone and also from the in vitro juvenile seedlings “IVJ”, whereas
outdoor seedlings “Juv” exhibited intermediate SAM dome height. SAM domes from the rejuvenated material “Rej”, from the in
vitro mature “IVM” and juvenile “IVJ” origins were also narrower than those from the outdoor seedlings “Juv” and to lesser
extent than those from the mature trees “Mat”. Overall, the mature source “Mat” displayed bigger and somehow sharper hemispherical
domes than those from “Rej” and “Juv”, physiologically more juvenile, or those from the in vitro origins “IVM” and “IVJ” which
looked flatter and smaller. SAM dome height, diameter D and H/D values varied also significantly according to the plastochron. More specifically, H, D, and H/D SAM differences between the five origins were not significant during the early plastochron phase corresponding to leaf initiation,
to become more salient as leaf structures started to elongate and to differentiate. This was particularly obvious for mature
tree “Mat” SAM dome shapes which showed at this stage much higher H/D values than the other SAM sources. A shape index S used for characterizing more accurately dome shape confirmed these trends. These observations provide additional arguments
to the view that juvenility in trees becomes more and more time- and shoot-tip restricted as ageing increases in the course
of time during the ontogenetical process and could be ultimately confined to the most organogenic phase of SAM, from which
shoot characteristics derive. 相似文献
76.
77.
Spine degeneration is a pathology that will affect 80% of the population. Since the intervertebral disks play an important role in transmitting loads through the spine, the aim of this study was to evaluate the biomechanical impact of disk properties on the load carried by healthy (Thompson grade I) and degenerated (Thompson grades III and IV) disks. A three-dimensional parametric poroelastic finite element model of the L4/L5 motion segment was developed. Grade I, grade II, and grade IV disks were modeled by altering the biomechanical properties of both the annulus and nucleus. Models were validated using published creep experiments, in which a constant compressive axial stress of 0.35 MPa was applied for 4 h. Pore pressure (PP) and effective stress (S(E)) were analyzed as a function of time following loading application (1 min, 5 min, 45 min, 125 min, and 245 min) and discal region along the midsagittal profile for each disk grade. A design of experiments was further implemented to analyze the influence of six disk parameters (disk height (H), fiber proportion (%F), drained Young's modulus (E(a),E(n)), and initial permeability (k(a),k(n)) of both the annulus and nucleus) on load-sharing for disk grades I and IV. Simulations of grade I, grade III, and grade IV disks agreed well with the available published experimental data. Disk height (H) had a significant influence (p<0.05) on the PP and S(E) during the entire loading history for both healthy and degenerated disk models. Young's modulus of the annulus (E(a)) significantly affected not only S(E) in the annular region for both disk grades in the initial creep response but also S(E) in the nucleus zone for degenerated disks with further creep response. The nucleus and annulus permeabilities had a significant influence on the PP distribution for both disk grades, but this effect occurred at earlier stages of loading for degenerated than for healthy disk models. This is the first study that investigates the biomechanical influence of both geometrical and material disk properties on the load transfer of healthy and degenerated disks. Disk height is a significant parameter for both healthy and degenerated disks during the entire loading. Changes in the annulus stiffness, as well as in the annulus and nucleus permeability, control load-sharing in different ways for healthy and degenerated disks. 相似文献
78.
Joshua M. Shulman Lori B. Chibnik Cristin Aubin Julie A. Schneider David A. Bennett Philip L. De Jager 《PloS one》2010,5(6)
Background
Recent genetic studies have identified a growing number of loci with suggestive evidence of association with susceptibility to Alzheimer''s disease (AD). However, little is known of the role of these candidate genes in influencing intermediate phenotypes associated with a diagnosis of AD, including cognitive decline or AD neuropathologic burden.Methods/Principal Findings
Thirty-two single nucleotide polymorphisms (SNPs) previously implicated in AD susceptibility were genotyped in 414 subjects with both annual clinical evaluation and completed brain autopsies from the Religious Orders Study and the Rush Memory and Aging Project. Regression analyses evaluated the relation of SNP genotypes to continuous measures of AD neuropathology and cognitive function proximate to death. A SNP in the zinc finger protein 224 gene (ZNF224, rs3746319) was associated with both global AD neuropathology (p = 0.009) and global cognition (p = 0.002); whereas, a SNP at the phosphoenolpyruvate carboxykinase locus (PCK1, rs8192708) was selectively associated with global cognition (p = 3.57×10−4). The association of ZNF224 with cognitive impairment was mediated by neurofibrillary tangles, whereas PCK1 largely influenced cognition independent of AD pathology, as well as Lewy bodies and infarcts.Conclusions/Significance
The findings support the association of several loci with AD, and suggest how intermediate phenotypes can enhance analysis of susceptibility loci in this complex genetic disorder. 相似文献79.
Bolduc JE Lewis LJ Aubin CE Geitmann A 《Biomechanics and modeling in mechanobiology》2006,5(4):227-236
Micro-indentation is a new experimental approach to assess physical cellular properties. Here we attempt to quantify the contribution of geometrical parameters to a cylindrical plant cell’s resistance to lateral deformation. This information is important to correctly interpret data obtained from experiments using the device, such as the local cellular stiffness in pollen tubes. We built a simple finite-element model of the micro-indentation interacting partners – micro-indenter, cell (pollen tube), and underlying substratum, that allowed us to manipulate geometric variables, such as geometry of the cell, cell radius, thickness of the cell wall and radius of the indenting stylus. Performing indentation experiments on this theoretical model demonstrates that all four parameters influence stiffness measurement and can therefore not be neglected in the interpretation of micro-indentation data. 相似文献
80.
Osteoprogenitor cell frequency in rat bone marrow stromal populations: role for heterotypic cell-cell interactions in osteoblast differentiation 总被引:4,自引:0,他引:4
Aubin JE 《Journal of cellular biochemistry》1999,72(3):396-410
Glucocorticoids, notably dexamethasone (Dex), have been reported to be a requirement for osteoprogenitor cell differentiation in young adult rat bone marrow stromal cell populations. We have reinvestigated the requirement for Dex and analyzed the frequency of osteoprogenitor cells present. Stromal cells were grown as primary or first subcultures in the presence or absence of Dex and their expression of osteogenic markers (alkaline phosphatase activity, hormone responsiveness, and matrix molecules, including type I collagen, osteopontin, bone sialoprotein, and osteocalcin), as well as their functional capacity to differentiate to form a mineralized bone nodule, were assessed. Dex increased, but was not an absolute requirement for, the expression of osteogenic markers. Bone nodule formation was plating cell density dependent and occurred under all combinations of treatment with or without Dex but was maximal when Dex was present in both the primary and secondary cultures. Dex increased CFU-F by approximately 2-fold, but increased CFU-O (osteoprogenitor cells; bone nodule forming cells) by 5- to 50-fold depending on the cell density and duration of treatment. Neither CFU-F nor CFU-O expression followed a linear relationship in limiting dilution analysis until very high cell densities were reached, suggesting cooperativity of cell types within the population and a multitarget phenomenon leading to osteoprogenitor differentiation. When a large number of nonadherent bone marrow cells or their conditioned medium was added to the stromal cells, osteoprogenitors comprised approximately 1/100 of plated adherent cells and their expression followed a linear, single-hit relationship. By contrast, rat skin fibroblasts or their conditioned medium totally inhibited bone nodule formation. These data support the hypothesis that in marrow stroma, as in other bone cell populations such as those from calvaria, there are at least two classes of osteoprogenitor cells: those differentiating in the absence of added glucocorticoid and those requiring glucocorticoid to differentiate, that more than one cell type is limiting for stromal osteoprogenitor differentiation suggesting a role for heterotypic cell-cell interactions in osteogenesis in this tissue, and that Dex may be acting directly and/or indirectly through accessory cells in the bone marrow to alter osteoprogenitor cell expression. 相似文献