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81.
Sylvia Y. M. Yao Amy M. L. Ng Manickavasagam Sundaram Carol E. Cass Stephen A. Baldwin James D. Young 《Molecular membrane biology》2013,30(2):161-167
In the present study, one has determined the relative role of plasma membrane equilibrative (Na+-independent) ENT nucleoside transport proteins (particularly ENT2) in the uptake of antiviral nucleoside analogues for comparison with the previously reported drug transport properties of concentrative (Na+-dependent) CNT nucleoside transport proteins. The human and rat nucleoside transport proteins hENT1, rENT1, hENT2 and rENT2 were produced in Xenopus oocytes and investigated for their ability to transport three 3'-deoxy-nucleoside analogues, ddC (2' 3'-dideoxycytidine), AZT (3'-azido-3'-deoxythymidine)and ddI (2' 3'-dideoxyinosine), used in human immunodeficiency virus (HIV) therapy. The results show, for the first time, that the ENT2 transporter isoform represents a mechanism for cellular uptake of these clinically important nucleoside drugs. Recombinant h/rENT2 transported ddC, ddI and AZT, whilst h/rENT1 transported only ddC and ddI. Relative to uridine, h/rENT2 mediated substantially larger fluxes of ddC and ddI than h/rENT1. Transplanting the amino-terminal half of rENT2 into rENT1 rendered rENT1 transport-positive for AZT and enhanced the uptake of both ddC and ddI, identifying this region as a major site of 3'-deoxy-nucleoside drug interaction. 相似文献
82.
Sylvia Lymburner Sarah McLeod Markus Purtzki Calvin Roskelley Zhaoming Xu 《The Journal of nutritional biochemistry》2013,24(6):1034-1040
Metastasis is the major cause of breast cancer mortality. The strength of cell adhesion to extracellular matrix is critical to cancer cell migration. Integrins, the primary mediators of cell to extra-cellular matrix adhesion, contain distinct divalent cation-binding sites. Binding of manganese and magnesium is vital to integrin-mediated cancer cell adhesion and migration. We hypothesized that zinc, a divalent cation, can modulate breast cancer metastasis through interfering with these divalent cation-dependent integrin-mediated cancer cell adhesion and migration. MDA-MB-231 cells were cultured in a zinc-depleted medium supplemented with 0 (control), 2.5, 5, 10, 25 and 50 μM of zinc to mimic severe zinc-deficiency, moderate zinc-deficiency, adequate zinc and three levels of zinc-supplementation: low-, moderate- and high-levels of zinc-supplementation, respectively. Zinc treatments had no effect on cellular zinc concentration, cell number and cell viability. Zinc at 5–50 μM reduced migration distance of MDA-MB-231 cells on fibronectin by 43–86% and migration rate on fibronectin by 72–90%. Zinc induced a dose-dependent inhibition of cell adhesion to fibronectin (R2=?0.98). Zinc at 10–50 μM reduced magnesium-facilitated cell adhesion to fibronectin in a dose-dependent manner (R2=?0.90). However, zinc had no effect on manganese-facilitated cell adhesion to fibronectin. Zinc at 5–50 μM caused rounding of the normally elongated, irregular-shaped MDA-MB-231 cells and disappearance of F-actin. Anti-integrin α5- and β1-subunit blocking antibodies inhibited magnesium-facilitated cell adhesion to fibronectin by 95 and 99%, respectively. In summary, zinc inhibited MDA-MB-231 cell migration on fibronectin by interfering with magnesium-dependent integrin-, likely integrin α5/β1-, mediated adhesion. 相似文献
83.
Calcareous grasslands are among the most species-rich plant communities in Europe with a particularly high nature conservation value. During the past centuries their distribution has markedly decreased, at least partly due to urbanization. Thus we investigated the effects of urbanization on species diversity along a spatio-temporal urbanization gradient from traditionally managed grassland to areas affected by urban developments, which was situated in the plains northwest of Munich, Germany. Both a RLQ analysis linking species and environmental traits, and a redundancy analysis of the plant community features showed that soil disturbance, soil sealing and mean temperature explained most of the environmental variation along the gradient. The species in urban habitats showed increased insect pollination, earlier flowering and prolonged seed longevity. While urbanization favored short-lived species with dysochorous dispersal, the reference grasslands harbored more wind-pollinated perennials with effective vegetative spread and relatively large, short-lived seeds. Compared to the urban sites, traditionally used grasslands had a higher species diversity, more threatened species and a lower proportion of non-natives. We conclude that even under conservation management, urban habitats are not capable of maintaining the original biodiversity. However, we also found threatened species occurring exclusively in urban sites. Hence, urbanization decreased the area and diversity of traditional calcareous grasslands, but it also established niches for endangered species which are not adapted to the living conditions in calcareous grasslands. 相似文献
84.
Jane Teas Sylvia Vena D. Lindsie Cone Mohammad Irhimeh 《Journal of applied phycology》2013,25(3):771-779
Daily consumption of seaweed has been proposed as a factor in explaining lower postmenopausal breast cancer (BC) incidence and mortality rates in Japan. This clinical trial assessed the impact of introducing seaweed- to non-seaweed-consuming American postmenopausal women. Fifteen healthy postmenopausal women were recruited for a 3-month single-blinded placebo controlled clinical trial; five had no history of BC (controls) and ten were BC survivors. Participants ingested ten capsules daily (5 g day?1) of placebo for 4 weeks, seaweed (Undaria) for 4 weeks, then placebo for another 4 weeks. Blood and urine samples were collected after each treatment period. Urinary human urokinase-type plasminogen activator receptor concentrations (uPAR) were analyzed by ELISA, and urine and serum were analyzed for protein expression using surface-enhanced laser desorption/ionization–time-of-flight mass spectrometry (SELDI-TOF-MS). Urinary creatinine standardized uPAR (in pg mL μg?1 creatinine) changed significantly between groups, decreasing by about half following seaweed supplementation (placebo 1, 1.5 (95 % CI, 0.9–2.1) and seaweed, 0.9 (95 % CI, 0.6–1.1) while placebo 2 returned to pre-seaweed concentration (1.7 (95 % CI, 1.2-2.2); p?=?0.01, ANOVA). One SELDI-TOF-MS-identified urinary protein (m/z 9,776) showed a similar reversible decrease with seaweed and is reported to be associated with cell attachment. One serum protein (m/z 8,928) reversibly increased with seaweed and may be the immunostimulatory complement activation C3a des-arginine. uPAR is higher among postmenopausal women generally, and for BC patients, it is associated with unfavorable BC prognosis. By lowering uPAR, dietary seaweed may help explain lower BC incidence and mortality among postmenopausal women in Japan. 相似文献
85.
Jannie J. van der Helm Reinier J. M. Bom Antoon W. Grünberg Sylvia M. Bruisten Maarten F. Schim van der Loeff Leslie O. A. Sabajo Henry J. C. de Vries 《PloS one》2013,8(7)
Background
Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname.Methods
Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition.Results
Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters.Conclusion
Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing. 相似文献86.
Sylvia Richter Xenia Gorny Judith Machts Gusalija Behnisch Torsten Wüstenberg Maike C. Herbort Thomas F. Münte Constanze I. Seidenbecher Bj?rn H. Schott 《PloS one》2013,8(1)
Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli. 相似文献
87.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献88.
Brigitta Ine Van Tussenbroek Tania Valdivia‐Carrillo Irene Teresa Rodríguez‐Virgen Sylvia Nashieli Marisela Sanabria‐Alcaraz Karina Jiménez‐Durán Kor Jent Van Dijk Guadalupe Judith Marquez‐Guzmán 《Ecology and evolution》2016,6(15):5542-5556
The high prevalence of dioecy in marine angiosperms or seagrasses (>50% of all species) is thought to enforce cross‐fertilization. However, seagrasses are clonal plants, and they may still be subject to sibling‐mating or bi‐parental inbreeding if the genetic neighborhood is smaller than the size of the genets. We tested this by determining the genetic neighborhoods of the dioecious seagrass Thalassia testudinum at two sites (Back‐Reef and Mid‐Lagoon) in Puerto Morelos Reef Lagoon, Mexico, by measuring dispersal of pollen and seeds in situ, and by fine‐scale spatial autocorrelation analysis with eight polymorphic microsatellite DNA markers. Prevalence of inbreeding was verified by estimating pairwise kinship coefficients; and by analysing the genotypes of seedlings grown from seeds in mesocosms. Average dispersal of pollen was 0.3–1.6 m (max. 4.8 m) and of seeds was 0.3–0.4 m (max. 1.8 m), resulting in a neighborhood area of 7.4 m2 (range 3.4–11.4 m2) at Back‐Reef and 1.9 (range 1.87–1.92 m2) at Mid‐Lagoon. Neighborhood area (Na) derived from spatial autocorrelation was 0.1–20.5 m2 at Back‐Reef and 0.1–16.9 m2 at Mid‐Lagoon. Maximal extensions of the genets, in 19 × 30 m plots, were 19.2 m (median 7.5 m) and 10.8 m (median 4.8 m) at Back‐Reef and Mid‐Lagoon. There was no indication of deficit or excess of heterozygotes nor were coefficients of inbreeding (FIS) significant. The seedlings did not show statistically significant deficit of heterozygotes (except for 1 locus at Back‐Reef). Contrary to our expectations, we did not find evidence of bi‐parental inbreeding in this dioecious seagrass with large genets but small genetic neighborhoods. Proposed mechanisms to avoid bi‐parental inbreeding are possible selection against homozygotes during fecundation or ovule development. Additionally, the genets grew highly dispersed (aggregation index Ac was 0.09 and 0.10 for Back‐Reef and Mid‐Lagoon, respectively); such highly dispersed guerrilla‐like clonal growth form likely increases the probability of crossing between different potentially unrelated genets. 相似文献
89.
Richard Nolz Asenbaum Ulrika Julia Furtner Ramona Woitek Sylvia Unterhumer Andreas Wibmer Alexander Prusa Christian Loewe Maria Schoder 《PloS one》2016,11(3)
PurposeTo define the diagnostic precision of non-specialized readers in the detection of type 2 endoleaks (T2EL) in arterial versus venous phase acquisitions, and to evaluate an approach for radiation dose reduction.MethodsThe pre-discharge and final follow-up multi-slice CT angiographies of 167 patients were retrospectively analyzed. Image data were separated into an arterial and a venous phase reading set. Two radiology residents assessed the reading sets for the presence of a T2EL, feeding vessels, and aneurysm sac size. Findings were compared with a standard of reference established by two experts in interventional radiology. The effective dose was calculated.ResultsOverall, experts detected 131 T2ELs, and 331 feeding vessels in 334 examinations. Persistent T2ELs causing aneurysm sac growth > 5 mm were detected in 20 patients. Radiation in arterial and venous phases contributed to a mean of 58.6% and 39.0% of the total effective dose. Findings of reader 1 and 2 showed comparable sensitivities in arterial sets of 80.9 versus 85.5 (p = 0.09), and in venous sets of 73.3 versus 79.4 (p = 0.15), respectively. Reader 1 and 2 achieved a significant higher detection rate of feeding vessels with arterial compared to venous set (p = 0.04, p < 0.01). Both readers correctly identified T2ELs with growing aneurysm sac in all cases, independent of the acquisition phase.ConclusionArterial acquisitions enable non-specialized readers an accurate detection of T2ELs, and a significant better identification of feeding vessels. Based on our results, it seems reasonable to eliminate venous phase acquisitions. 相似文献
90.
Roma Chilengi Michelo Simuyandi Lauren Beach Katayi Mwila Sylvia Becker-Dreps Devy M. Emperador Daniel E. Velasquez Samuel Bosomprah Baoming Jiang 《PloS one》2016,11(3)