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41.
Rady PL Surendran S Vu AT Hawkins JC Michals-Matalon K Tyring SK Merren J Kumar AK Matalon R 《Genetic testing》2002,6(3):211-215
Sanfilippo A syndrome is an autosomal recessive lysosomal storage disease. This disease was reported in the Cayman Islands population with carrier frequency of 1/7 to 1/10 in the West Bay district of Grand Cayman. The carrier testing of Sanfilippo A disease for families at risk was carried out using the thermal characteristics of sulfamidase activity. In the present study, a search for mutations in the sulfamidase gene in an index family was performed. In addition, 77 individuals, relatives of children with Sanfilippo A syndrome, were also studied by single-strand conformation polymorphism (SSCP), restriction fragment-length polymorphism (RFLP) analyses, and sequencing. A single mutation, G746A (R245H), was found in the family, with the patient being homozygous and both parents and 1 of the 3 siblings being carriers. Among the 77 family members of the patient with Sanfilippo syndrome, the same mutation was found among carriers of the disease. The finding of a single mutation supports the idea of a founder effect, which facilitates accurate carrier identification of Sanfilippo A syndrome in the population of Cayman Islands. 相似文献
42.
Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells 下载免费PDF全文
The linker region of Syk and ZAP70 tyrosine kinases plays an important role in regulating their function. There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Here we studied the roles of the other two tyrosines, Tyr342 and Tyr346 of Syk, in Fc epsilon RI-mediated signaling. Antigen stimulation resulted in Tyr342 phosphorylation in mast cells. Syk with Y342F mutation failed to reconstitute Fc epsilon RI-initiated histamine release. In the Syk Y342F-expressing cells there was dramatically impaired receptor-induced phosphorylation of multiple signaling molecules, including LAT, SLP-76, phospholipase C-gamma2, but not Vav. Compared to wild-type Syk, Y342F Syk had decreased binding to phosphorylated immunoreceptor tyrosine-based activation motifs and reduced kinase activity. Surprisingly, mutation of Tyr346 had much less effect on Fc epsilon RI-dependent mast cell degranulation. An anti-Syk-phospho-346 tyrosine antibody indicated that antigen stimulation induced only a very minor increase in the phosphorylation of this tyrosine. Therefore, Tyr342, but not Tyr346, is critical for regulating Syk in mast cells and the function of these tyrosines in immune receptor signaling appears to be different from what has been previously reported for the equivalent residues of ZAP70. 相似文献
43.
Mismatch Repair in Escherichia coli Cells Lacking Single-Strand Exonucleases ExoI, ExoVII, and RecJ 下载免费PDF全文
Reuben S. Harris Kimberly J. Ross Mary-Jane Lombardo Susan M. Rosenberg 《Journal of bacteriology》1998,180(4):989-993
In vitro, the methyl-directed mismatch repair system of Escherichia coli requires the single-strand exonuclease activity of either ExoI, ExoVII, or RecJ and possibly a fourth, unknown single-strand exonuclease. We have created the first precise null mutations in genes encoding ExoI and ExoVII and find that cells lacking these nucleases and RecJ perform mismatch repair in vivo normally such that triple-null mutants display normal mutation rates. ExoI, ExoVII, and RecJ are either redundant with another function(s) or are unnecessary for mismatch repair in vivo. 相似文献
44.
Melissa P. L. Chan Robert S. Weinhold Reuben Thomas Julia M. Gohlke Christopher J. Portier 《PloS one》2015,10(12)
A growing body of evidence has found that mortality rates are positively correlated with social inequalities, air pollution, elevated ambient temperature, availability of medical care and other factors. This study develops a model to predict the mortality rates for different diseases by county across the US. The model is applied to predict changes in mortality caused by changing environmental factors. A total of 3,110 counties in the US, excluding Alaska and Hawaii, were studied. A subset of 519 counties from the 3,110 counties was chosen by using systematic random sampling and these samples were used to validate the model. Step-wise and linear regression analyses were used to estimate the ability of environmental pollutants, socio-economic factors and other factors to explain variations in county-specific mortality rates for cardiovascular diseases, cancers, chronic obstructive pulmonary disease (COPD), all causes combined and lifespan across five population density groups. The estimated models fit adequately for all mortality outcomes for all population density groups and, adequately predicted risks for the 519 validation counties. This study suggests that, at local county levels, average ozone (0.07 ppm) is the most important environmental predictor of mortality. The analysis also illustrates the complex inter-relationships of multiple factors that influence mortality and lifespan, and suggests the need for a better understanding of the pathways through which these factors, mortality, and lifespan are related at the community level. 相似文献
45.
Maud Condomines Jon Arnason Reuben Benjamin Gertrude Gunset Jason Plotkin Michel Sadelain 《PloS one》2015,10(6)
Adoptive T cell therapy represents a promising treatment for cancer. Human T cells engineered to express a chimeric antigen receptor (CAR) recognize and kill tumor cells in a MHC-unrestricted manner and persist in vivo when the CAR includes a CD28 costimulatory domain. However, the intensity of the CAR-mediated CD28 activation signal and its regulation by the CTLA-4 checkpoint are unknown. We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z) displayed the same proliferation and anti-tumor abilities than T cells expressing a CD3 zeta-based CAR (19z1) costimulated through the CD80/CD28, ligand/receptor pathway. Repeated in vitro antigen-specific stimulations indicated that 19-28z+ T cells secreted higher levels of Th1 cytokines and showed enhanced proliferation compared to those of 19z1+ or 19z1-CD80+ T cells. In an aggressive pre-B cell leukemia model, mice treated with 19-28z+ T cells had 10-fold reduced tumor progression compared to those treated with 19z1+ or 19z1-CD80+ T cells. shRNA-mediated CTLA-4 down-regulation in 19z1-CD80+ T cells significantly increased their in vivo expansion and anti-tumor properties, but had no effect in 19-28z+ T cells. Our results establish that CTLA-4 down-regulation may benefit human adoptive T cell therapy and demonstrate that CAR design can elude negative checkpoints to better sustain T cell function. 相似文献
46.
When the lysoglycerophospholipid (GPL) acyltransferase At1g78690 from Arabidopsis thaliana is over-expressed in Escherichiacoli a headgroup acylated GPL, acyl phosphatidylglycerol (PG), accumulates despite that in vitro this enzyme catalyzes the transfer of an acyl chain from acyl-CoA to the sn-2 position of 1-acyl phosphatidylethanolamine (PE) or 1-acyl PG to form the sn-1, sn-2, di acyl PE and PG respectively; it does not acylate PG to form acyl PG. To begin to understand why the overexpression of a lyso GPL acyltransferase leads to the accumulation of a headgroup acylated GPL in E. coli we investigated the headgroup specificity of At1g78690. Using membranes prepared from E. coli overexpressing At1g78690, we assessed the ability of At1g78690 to catalyze the transfer of acyl chains from acyl-coenzyme A to a variety of lyso GPL acyl acceptors including lyso-phosphatidic acid (PA), -phosphatidylcholine (PC), -phosphatidylserine (PC), -phosphatidylinositol (PI) and three stereoisoforms of bis(monoacylglycero)phosphate (BMP). The predicted products were formed when lyso PI and lyso PC were used as the acyl acceptor but not with lyso PC or lyso PA. In addition, At1g78690 robustly acylates two BMP isoforms with sn-2 and/or sn-2′ hydroxyls in the R-stereoconfiguration, but not the BMP isoform with the sn-2 and sn-2′ hydroxyls in the S-stereoconfiguration. This strongly suggests that At1g78690 is stereoselective for hydroxyls with R-stereochemistry. In addition, this robust acylation of BMPs by At1g78690, which yields acyl PG like molecules, may explain the mechanism by which At1g78690 so strikingly alters the lipid composition of E. coli. 相似文献
47.
Reuben Clements Darmaraj Mark Rayan Abdul Wahab Ahmad Zafir Arun Venkataraman Raymond Alfred Junaidi Payne Laurentius Ambu Dionysius Shankar Kumar Sharma 《Biodiversity and Conservation》2010,19(4):1115-1136
Three of Malaysia’s endangered large mammal species are experiencing contrasting futures. Populations of the Sumatran rhino
(Dicerorhinus sumatrensis) have dwindled to critically low numbers in Peninsular Malaysia (current estimates need to be revised) and the state of Sabah
(less than 40 individuals estimated). In the latter region, a bold intervention involving the translocation of isolated rhinos
is being developed to concentrate them into a protected area to improve reproduction success rates. For the Asian elephant
(Elephas maximus), recently established baselines for Peninsular Malaysia (0.09 elephants/km2 estimated from one site) and Sabah (between 0.56 and 2.15 elephants/km2 estimated from four sites) seem to indicate globally significant populations based on dung count surveys. Similar surveys
are required to monitor elephant population trends at these sites and to determine baselines elsewhere. The population status
of the Malayan tiger (Panthera tigris jacksoni) in Peninsular Malaysia, however, remains uncertain as only a couple of scientifically defensible camera-trapping surveys
(1.66 and 2.59 tigers/100 km2 estimated from two sites) have been conducted to date. As conservation resources are limited, it may be prudent to focus
tiger monitoring and protection efforts in priority areas identified by the National Tiger Action Plan for Malaysia. Apart
from reviewing the conservation status of rhinos, elephants and tigers and threats facing them, we highlight existing and
novel conservation initiatives, policies and frameworks that can help secure the long-term future of these iconic species
in Malaysia. 相似文献
48.
Plants are known to be highly responsive to environmental heterogeneity and normally allocate more biomass to organs that grow in richer patches. However, recent evidence demonstrates that plants can discriminately allocate more resources to roots that develop in patches with increasing nutrient levels, even when their other roots develop in richer patches. Responsiveness to the direction and steepness of spatial and temporal trajectories of environmental variables might enable plants to increase their performance by improving their readiness to anticipated resource availabilities in their immediate proximity. Exploring the ecological implications and mechanisms of trajectory-sensitivity in plants is expected to shed new light on the ways plants learn their environment and anticipate its future challenges and opportunities.Key words: Gradient perception, phenotypic plasticity, anticipatory responses, plant behavior, plant learningNatural environments present organisms with myriad challenges of surviving and reproducing under changing conditions.1 Depending on its extent, predictability and costs, environmental heterogeneity may select for various combinations of genetic differentiation and phenotypic plasticity.2–6 However, phenotypic plasticity is both limited and costly.7 One of the main limitations of phenotypic plasticity is the lag between the perception of the environment and the time the products of the plastic responses are fully operational.7 For instance, the developmental time of leaves may significantly limit the adaptive value of their plastic modification due to mismatches between the radiation levels and temperatures prevailing during their development and when mature and fully functional.8,9 Accordingly, selection is expected to promote responsiveness to cues that bear information regarding the probable future environment.9,10Indeed, anticipatory responses are highly prevalent, if not universal, amongst living organisms. Whether through intricate cerebral processes, such as in vertebrates, nervous coordination, as in Echinoderms,11 or by relatively rudimentary non-neural processes, such as in plants12 and bacteria,13 accumulating examples suggest that virtually all known life forms are able to not only sense and plastically respond to their immediate environment but also anticipate probable future conditions via environmental correlations.10Perhaps the best known example of plants'' ability to anticipate future conditions is their responsiveness to spectral red/far-red cues, which is commonly tightly correlated with future probability of light competition.14 Among others, plants have been shown to respond to cues related to anticipated herbivory15,16 and nitrogen availability.17 Imminent stress is commonly anticipated by the perception of a prevailing stress. For example, adaptation to anticipated severe stress was demonstrated to be inducted by early priming by sub-acute drought,18 root competition19 and salinity.20Future conditions can also be anticipated by gradient perception: because resource and stress levels are often changing along predictable spatial and temporal trajectories, spatio-temporal dynamics of environmental variables might convey information regarding anticipated growth conditions (Fig. 1). For example, the order of changes in day length, rather than day length itself, are known to assist plants in differentiating fall from spring and thus avoid blooming in the wrong season.21 In addition, responsiveness to environmental gradients as such, i.e., sensitivity to the direction and steepness of environmental trajectories, independently from the stationary levels of the same factors, has been demonstrated in higher organisms, such as the perception of acceleration in contrast to velocity;22 and the dynamics of skin temperature in contrast to stationary skin temperature;23 where the adaptive value of the second-order derivatives of environmental factors is paramount. Similar perception capabilities have also been demonstrated in rudimentary life forms such as bacteria (reviewed in refs. 13 and 24) and plants.25,26 Specifically, perception of environmental trajectories might assist organisms to both anticipate future conditions and better utilize the more promising patches in their immediate environment.27,28Open in a separate windowFigure 1Trajectory sensitivity in plants. The hypothetical curves depict examples of spatio-temporal trajectories of resource availability, which might be utilized by plants to increase foraging efficiency in newly-encountered patches. When young or early-in-the-season (segment 1–2), plants are expected to allocate more resources to roots that experience the most promising (steepest increases or shallowest decreases) resource availabilities (e.g., allocating more resources to organs in INC-1 than INC-2). In addition, plants are predicted to avoid allocation to roots experiencing decreasing trajectories (DEC, segment 1–2); although temporarily more abundant with resources, such DEC patches are expected to become poorer than alternative patches in the longer run (segment 2–3).29 However, responsiveness to environmental trajectories is only predicted where the expected period of resource uptake is relatively long, e.g., when plants are still active in segment 2–3, a stipulation which might not be fulfilled in e.g., short-living annuals with life span shorter than segment 1–2.In a recent study, Pisum plants have been demonstrated to be sensitive to temporal changes in nutrient availabilities. Specifically, plants allocated greater biomass to roots growing under dynamically-improving nutrient levels than to roots that grew under continuously higher, yet stationary or deteriorating, nutrient availabilities.29 Allocation to roots in poorer patches might seem maladaptive if only stationary nutrient levels are accounted for, and indeed-almost invariably, plants are known to allocate more resources to organs that experience higher (non-toxic) resource levels (reviewed in ref. 33). Accordingly, the new findings suggest that rather than merely responding to the prevailing nutrient availabilities, root growth and allocation are also responsive to trajectories of nutrient availabilities (Fig. 1).10Although Shemesh et al.29 demonstrated trajectory-sensitivity of individual roots to temporal gradient of nutrient availabilities, it is likely that this sensitivity helps plants sense spatial gradients, whereby root tips perceive changes in growth conditions as they move through space.34 Interestingly, because the trajectory-sensitivity was observed when whole roots were subjected to changing nutrient levels, it is likely that trajectory sensitivity in roots is based on the integration of sensory inputs perceived by yet-to-be-determined parts of the root over time, i.e., temporal sensitivity/memory (e.g. reviewed in ref. 35), rather than on the integration of sensory inputs at different locations on the same individual roots (i.e., spatial sensitivity).Besides the direction of change, it is hypothesized that plants are also sensitive to the steepness of environmental trajectories (Fig. 1). This might be especially crucial in short-living annuals, which are expected to only be responsive to trajectories steep enough to be indicative of changes in growth conditions before the expected termination of the growth season (Fig. 1).Studying responsiveness to environmental variability is pivotal for understanding the ecology and evolution of any living organism. However, until recently most attention has been given to the study of responses to stationary spatial and temporal heterogeneities in growth conditions. Exploring the ecological implications and mechanisms of trajectory sensitivity in plants is expected to shed new light on the ways plants learn their immediate environment and anticipate its future challenges and opportunities. 相似文献
49.
Ja-an Annie Ho Li-Chen Wu Li-Hui Chang Kuo-Chu Hwang Jih-Ru Reuben Hwu 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(2):172-176
Immunoglobulin E (IgE)-mediated type I allergies affect over 25% of the world's population; they are among the most common diseases in developed countries. Therefore, simple and rapid in vivo and in vitro methods for diagnosing allergies are becoming increasingly important. In this paper, we demonstrate the feasibility of using sulforhodamine B, a fluorescent dye, entrapped inside immunoliposomes, the outer surfaces of which were sensitized with IgE, as a signal amplifier for the development of a simple, rapid, and inexpensive colorimetric affinity chromatographic immunoassay for the detection of total IgE in serum. This assay operates based on competition between standards (or human serum samples) containing IgE and IgE-sensitized immunoliposomes for the limited number of antigen binding sites of immobilized anti-IgE antibodies at the antigen capture (AC) zone on the nitrocellulose membranes. The color density of the AC zone is indirectly proportional to the number of IgE units present in the test sample. The detection limit of this liposome-based immunoaffinity chromatographic assay was 0.37 ng in IgE-free serum solution (equivalent to 20 μL of a 18.5 ng mL−1 solution). A commercially available ELISA kit was used as a reference method to validate the proposed assay through the analysis of three human serum samples. 相似文献
50.