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221.
Berahovich RD Zabel BA Penfold ME Lewén S Wang Y Miao Z Gan L Pereda J Dias J Slukvin II McGrath KE Jaen JC Schall TJ 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(9):5130-5139
Since the discovery that CXCR7 binds to CXCL12/SDF-1α, the role of CXCR7 in CXCL12-mediated biological processes has been under intensive scrutiny. However, there is no consensus in the literature on the expression of CXCR7 protein by peripheral blood cells. In this study we analyzed human and mouse leukocytes and erythrocytes for CXCR7 protein expression, using a competitive CXCL12 binding assay as well as by flow cytometry and immunohistochemistry using multiple CXCR7 Abs. CXCR7(-/-) mice were used as negative controls. Together, these methods indicate that CXCR7 protein is not expressed by human peripheral blood T cells, B cells, NK cells, or monocytes, or by mouse peripheral blood leukocytes. CXCR7 protein is, however, expressed on mouse primitive erythroid cells, which supply oxygen to the embryo during early stages of development. These studies therefore suggest that, whereas CXCR7 protein is expressed by primitive RBCs during murine embryonic development, in adult mammals CXCR7 protein is not expressed by normal peripheral blood cells. 相似文献
222.
Max Lataillade Jennifer Chiarella Rong Yang Steven Schnittman Victoria Wirtz Jonathan Uy Daniel Seekins Mark Krystal Marco Mancini Donnie McGrath Birgitte Simen Michael Egholm Michael Kozal 《PloS one》2010,5(6)
Background
CASTLE compared the efficacy of atazanavir/ritonavir with lopinavir/ritonavir, each in combination with tenofovir-emtricitabine in ARV-naïve subjects from 5 continents.Objectives
Determine the baseline rate and clinical significance of TDR mutations using ultra-deep sequencing (UDS) in ARV-naïve subjects in CASTLE.Methods
A case control study was performed on baseline samples for all 53 subjects with virologic failures (VF) at Week 48 and 95 subjects with virologic successes (VS) randomly selected and matched by CD4 count and viral load. UDS was performed using 454 Life Sciences/Roche technology.Results
Of 148 samples, 141 had successful UDS (86 subtype B, 55 non-B subtypes). Overall, 30.5% of subjects had a TDR mutation at baseline; 15.6% only had TDR(s) at <20% of the viral population. There was no difference in the rate of TDRs by B (30.2%) or non-B subtypes (30.9%). VF (51) and VS (90) had similar rates of any TDRs (25.5% vs. 33.3%), NNRTI TDRs (11.1% vs.11.8%) and NRTI TDRs (24.4% vs. 25.5%). Of 9 (6.4%) subjects with M184V/I (7 at <20% levels), 6 experienced VF. 16 (11.3%) subjects had multiple TAMs, and 7 experienced VF. 3 (2.1%) subjects had both multiple TAMs+M184V, and all experienced VF. Of 14 (9.9%) subjects with PI TDRs (11 at <20% levels): only 1 experienced virologic failure. The majority of PI TDRs were found in isolation (e.g. 46I) at <20% levels, and had low resistance algorithm scores.Conclusion
Among a representative sample of ARV-naïve subjects in CASTLE, TDR mutations were common (30.5%); B and non-B subtypes had similar rates of TDRs. Subjects with multiple PI TDRs were infrequent. Overall, TDRs did not affect virologic response for subjects on a boosted PI by week 48; however, a small subset of subjects with extensive NRTI backbone TDR patterns experienced virologic failure. 相似文献223.
Four genes have recently been proposed as candidates for dyslexia: dyslexia susceptibility 1 candidate 1 (DYX1C1), roundabout Drosophila homolog 1 (ROBO1), doublecortin domain-containing protein 2 (DCDC2) and KIAA0319. Each gene is implicated in global brain-development processes such as neural migration and axonal guidance, with the exception of DYX1C1, the function of which is still unknown. The most immediate clinical prospect of the discovery of these genes is the possibility of early identification of dyslexia via genetic screening. However, research efforts have yet to identify a functional mutation in any of these genes. When causal variants are identified, they will need to be considered within a multifactorial framework, which is likely to involve gene-gene and gene-environment interactions, to make accurate predictions of diagnostic status. 相似文献
224.
Reini W Bretveld Chris MG Thomas Paul TJ Scheepers Gerhard A Zielhuis Nel Roeleveld 《Reproductive biology and endocrinology : RB&E》2006,4(1):30
Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system
through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference
with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide
exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function
of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation:
1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition
and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms
are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation
of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies,
exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy,
spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal
function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity,
it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining
the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive
effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in
this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both
in toxicological and epidemiological settings. 相似文献
225.
226.
Effects of pregnancy and chronic exercise on maternal cardiac structure and function 总被引:3,自引:0,他引:3
Wolfe LA Preston RJ Burggraf GW McGrath MJ 《Canadian journal of physiology and pharmacology》1999,77(11):909-917
This study examined the interactive effects of pregnancy and aerobic conditioning on maternal cardiac structure and function. Effects of closely monitored cycle ergometer conditioning were studied during the second (TM2) and third trimesters (TM3) in 22 previously sedentary pregnant women (exercised group, EG) and a nonexercising pregnant control group with similar characteristics (CG, n = 19). Subjects were studied in the resting state by two-dimensional echocardiography and during cycle ergometer exercise at three steady-state power outputs at the start of TM2 (ENTRY), at the end of TM2 and TM3 (postconditioning), and 3-4 months postpartum (NPR, nonpregnant reference, CG only). Aerobic conditioning did not increase left ventricular dimensions beyond those attributable to pregnancy itself. In addition, in contrast with previous studies of nonpregnant women, physical conditioning during pregnancy did not reduce heart rate (HR) in the resting state. During exercise, the slope of the HR versus oxygen uptake (VO2) regression decreased significantly between preconditioning and the end of TM3 in the EG, suggesting that training-induced reductions in HR become more evident with increasing exercise intensity. Also, significant reductions in oxygen pulse (VO2/HR) were observed at all three work rates in the CG, but not in the EG. These findings support the hypothesis that the cardiovascular effects of aerobic conditioning are obscured by more powerful effects of pregnancy in the resting state but become "unmasked" during strenuous exercise. 相似文献
227.
Measurement of the osmotic response of a cell in the presence of cryoprotectant facilitates the determination of permeability coefficients which, in turn, can be used to design cryopreservation protocols which minimize osmotic stress. One problem encountered in determining permeability coefficients, using the Kedem-Katchalsky (K-K) model of membrane permeability, is that several combinations of the three passive coupled transport coefficients, namely, hydraulic permeability (L(p), microm min(-1) atm(-1)), solute permeability (P(gly), microm s(-1)), and the reflection coefficient (sigma), can give a similar fit to the measured data. A method for determining the "correct" set of coefficients is suggested. The osmotic response of 10 metaphase II mouse oocytes was measured on perfusion with 1.5 mol L(-1) glycerol at 24 degrees C. For 8 of 10 oocytes perfused, two combinations of L(p), P(gly), and sigma gave a predicted response which closely matched the measured osmotic response, depending upon the initial estimates supplied to the software for these parameters. For the remaining two oocytes, similar values for the permeability coefficients were generated regardless of the initial estimates. To determine the correct set of parameters, the K-K equations were used to predict experimental conditions for which volumetric histories would be distinctly different for the two sets of "best-fit parameters," and then additional experimental data were compared to these predictions. Thus a further three oocytes were perfused with 0.2 or 0.5 mol L(-1) glycerol in the absence of nonpermeating solute. In the presence of both 0.2 and 0.5 mol L(-1) glycerol, L(p) = 2.11 +/- 0.69, P(gly) = 0.0016 +/- 0.0015, and sigma = 0.44 +/- 0.11 yielded a very poor fit to the measured response while L(p) = 0.98 +/- 0.70, P(gly) = 0. 0031 +/- 0.0021, and sigma = 0.91 +/- 0.15 yielded a close fit to the measured response. Thus the latter combination of coefficients was taken to be correct. 相似文献
228.
Cellular compartmentation of Zn in the leaves of the
hyperaccumulator Thlaspi caerulescens was investigated
using energy-dispersive x-ray microanalysis and single-cell sap
extraction. Energy-dispersive x-ray microanalysis of frozen, hydrated
leaf tissues showed greatly enhanced Zn accumulation in the epidermis
compared with the mesophyll cells. The relative Zn concentration in the
epidermal cells correlated linearly with cell length in both young and
mature leaves, suggesting that vacuolation of epidermal cells may
promote the preferential Zn accumulation. The results from single-cell
sap sampling showed that the Zn concentrations in the epidermal
vacuolar sap were 5 to 6.5 times higher than those in the
mesophyll sap and reached an average of 385 mm in plants
with 20,000 μg Zn g−1 dry weight of shoots. Even when
the growth medium contained no elevated Zn, preferential Zn
accumulation in the epidermal vacuoles was still evident. The
concentrations of K, Cl, P, and Ca in the epidermal sap generally
decreased with increasing Zn. There was no evidence of association of
Zn with either P or S. The present study demonstrates that Zn is
sequestered in a soluble form predominantly in the epidermal vacuoles
in T. caerulescens leaves and that mesophyll cells are
able to tolerate up to at least 60 mm Zn in their sap.Different mechanisms have been proposed to explain the tolerance
of plants to toxic heavy metals (Baker and Walker, 1990; Verkleij and
Schat, 1990). Some tolerant plant species, the so-called
“excluders,” use exclusion mechanisms by which uptake and/or
root-to-shoot transport of heavy metals are restricted. Other tolerant
plant species are able to cope with elevated concentrations of toxic
metals inside of their tissues through production of metal-binding
compounds, cellular and subcellular compartmentation, or alterations of
metabolism.An extreme strategy for metal tolerance that is in sharp contrast to
metal exclusion is “hyperaccumulation,” a term that was originally
used by Brooks et al. (1977) to describe plants that can accumulate
more than 1,000 μg Ni g−1 dry weight in their
aerial parts. Approximately 400 taxa of terrestrial plants have been
identified as hyperaccumulators of various heavy metals, with about 300
being Ni hyperaccumulators (Baker and Brooks 1989; Brooks, 1998). Only
16 species of Zn hyperaccumulators, which are defined as being able to
accumulate more than 10,000 μg Zn g−1 in the
aboveground parts on a dry weight basis in their natural habitat
(Brooks, 1998), have been reported. Thlaspi caerulescens J.
& C. Presl (Brassicaceae) is the best-known example of a Zn/Cd
hyperaccumulator. Under hydroponic culture conditions T.
caerulescens can accumulate up to 25,000 to 30,000 μg Zn
g−1 dry weight in the shoots without showing any
toxicity symptoms or reduction in growth (Brown et al., 1996a; Shen et
al., 1997). Recently, there has been a surge of interest in the
phenomenon of heavy-metal hyperaccumulation because this property may
be exploited in the remediation of heavy-metal-polluted soils through
phytoextraction and phytomining (McGrath et al., 1993; Brown et al.,
1995b; Robinson et al., 1997).The mechanisms for metal hyperaccumulation are not fully understood,
and this is particularly true in the case of the Zn/Cd
hyperaccumulators. To cope with the consequence of hyperaccumulation,
plants must also be hypertolerant to the heavy metals that accumulate.
Recent studies comparing the different populations of T.
caerulescens have shown that hyperaccumulation of Zn is a
constitutive property, although the traits are probably separate from
those for tolerance (Baker et al., 1994; Meerts and Van Isacker, 1997).
Compared with the nonaccumulating species, T. caerulescens
possesses an enhanced capacity to take up Zn and transport it from
roots to shoots (Baker et al., 1994; Brown et al., 1995a; Shen et al.,
1997). Lasat et al. (1996) found that roots of T.
caerulescens and the nonaccumulator Thlaspi arvense had
similar apparent Km values for
Zn2+, but that the
Vmax in the former was 4.5-fold higher than
that in the latter species, indicating that the hyperaccumulator
T. caerulescens possessed more
Zn2+-transport sites in the plasma membranes of
root cells. Shen et al. (1997) showed that T. caerulescens
was much more effective in exporting the Zn that was accumulated
previously in roots to the shoots than an intermediate accumulator
species, Thlaspi ochrolucum. Organic acids such as malic
acid have been suggested to play a key role in shuttling Zn from
cytoplasm to vacuoles (Mathys, 1977). However, the
low affinity of malate to chelate Zn (stability constant
pK = 3.5 at infinite dilution) does not favor this
hypothesis. Moreover, high concentrations of malate found in the shoot
tissues of T. caerulescens appear to be a constitutive
property (Tolrà et al., 1996; Shen et al., 1997).The extraordinary tolerance of hyperaccumulator plants must also
involve compartmentation of toxic metals at the cellular and
subcellular levels. Vázquez et al. (1992, 1994) studied
localization of Zn in the root and leaf tissues of T.
caerulescens using EDXMA. They compared two methods of sample
preparation and found that Na2S fixation was not
suitable for preventing the loss of metal ions from the samples. Using
cryofixation and freeze substitution, they showed that Zn accumulated
mainly in the vacuoles as electron-dense deposits. Many vacuoles of
leaf-epidermal and subepidermal cells contained globular crystals that
were very rich in Zn. However, it is not known whether the Zn-rich,
globular crystal deposits occur inside of the leaf vacuoles in vivo or
if they are artifacts caused by sample preparation. Also, the technique
used by Vázquez et al. (1992, 1994) allows only semiquantitative
determination of Zn concentrations.In this study we used two techniques to investigate cellular
compartmentation of Zn in the leaves of T. caerulescens. The
first utilized EDXMA of frozen, hydrated tissue to survey the
distribution patterns of Zn and other elements across different leaf
cells. The second method involved sampling sap from single cells using
microcapillaries, followed by fully quantitative determination of Zn
and other elements using EDXMA. 相似文献
229.
230.