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71.
Michele Carbone Erin G. Flores Mitsuru Emi Todd A. Johnson Tatsuhiko Tsunoda Dusty Behner Harriet Hoffman Mary Hesdorffer Masaki Nasu Andrea Napolitano Amy Powers Michael Minaai Francine Baumann Peter Bryant-Greenwood Olivia Lauk Michaela B. Kirschner Walter Weder Isabelle Opitz Harvey I. Pass Giovanni Gaudino Sandra Pastorino Haining Yang 《PLoS genetics》2015,11(12)
We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). 相似文献
72.
Takuya Hara Emi Kobayashi Kohei Ohtsubo Shogo Kumada Mikako Kanazawa Tomoko Abe Ryuuichi D. Itoh Makoto T. Fujiwara 《PloS one》2015,10(3)
Leaf tissues of plants usually contain several types of idioblasts, defined as specialized cells whose shape and contents differ from the surrounding homogeneous cells. The spatial patterning of idioblasts, particularly of trichomes and guard cells, across the leaf epidermis has received considerable attention as it offers a useful biological model for studying the intercellular regulation of cell fate and patterning. Excretory idioblasts in the leaves of the aquatic monocotyledonous plant Egeria densa produced light blue autofluorescence when irradiated with ultraviolet light. The use of epifluorescence microscopy to detect this autofluorescence provided a simple and convenient method for detecting excretory idioblasts and allowed tracking of those cells across the leaf surfaces, enabling quantitative measurement of the clustering and spacing patterns of idioblasts at the whole leaf level. Occurrence of idioblasts was coordinated along the proximal–distal, medial–lateral, and adaxial–abaxial axes, producing a recognizable consensus spatial pattern of idioblast formation among fully expanded leaves. Idioblast clusters, which comprised up to nine cells aligned along the proximal–distal axis, showed no positional bias or regularity in idioblast-forming areas when compared with singlet idioblasts. Up to 75% of idioblasts existed as clusters on every leaf side examined. The idioblast-forming areas varied between leaves, implying phenotypic plasticity. Furthermore, in young expanding leaves, autofluorescence was occasionally detected in a single giant vesicle or else in one or more small vesicles, which eventually grew to occupy a large portion of the idioblast volume as a central vacuole. Differentiation of vacuoles by accumulating the fluorescence substance might be an integral part of idioblast differentiation. Red autofluorescence from chloroplasts was not detected in idioblasts of young expanding leaves, suggesting idioblast differentiation involves an arrest in chloroplast development at a very early stage, rather than transdifferentiation of chloroplast-containing epidermal cells. 相似文献
73.
To establish a non-radioactive, cell-free detection system for protein N-myristoylation, metabolic labeling in a cell-free protein synthesis system using bioorthogonal myristic acid analogues was performed. After Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) with a biotin tag, the tagged proteins were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and blotted on a polyvinylidene fluoride (PVDF) membrane, and then protein N-myristoylation was detected by enhanced chemiluminescence (ECL) using horseradish peroxidase (HRP)-conjugated streptavidin. The results showed that metabolic labeling in an insect cell-free protein synthesis system using an azide analogue of myristic acid followed by CuAAC with alkynyl biotin was the most effective strategy for cell-free detection of protein N-myristoylation. To determine whether the newly developed detection method can be applied for the detection of novel N-myristoylated proteins from complementary DNA (cDNA) resources, four candidate cDNA clones were selected from a human cDNA resource and their susceptibility to protein N-myristoylation was evaluated using the newly developed strategy. As a result, the products of three cDNA clones were found to be novel N-myristoylated protein, and myristoylation-dependent specific intracellular localization was observed for two novel N-myristoylated proteins. Thus, the metabolic labeling in an insect cell-free protein synthesis system using bioorthogonal azide analogue of myristic acid was an effective strategy to identify novel N-myristoylated proteins from cDNA resources. 相似文献
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76.
Eriko Nishimura Emi Suzaki Mami Irie Hisae Nagashima Tadaki Hirose 《Ecological Research》2010,25(2):383-393
Light climates strongly influence plant architecture and mass allocation. Using the metamer concept, we quantitatively described
branching architecture and growth of Chenopodium album plants grown solitarily or in a dense stand. Metamer is a unit of plant construction that is composed of an internode and
the upper node with a leaf and a subtended axillary bud. The number of metamers on the main-axis stem increased with plant
growth, but did not differ between solitary and dense-stand plants. Solitary plants had shorter thicker internodes with branches
larger in size and number than the plant in the dense stand. Leaf area on the main stem was not different. Larger leaf area
in solitary plants was due to a larger number of leaves on branches. Leaf mass per area (LMA) was higher in solitary plants.
It did not significantly differ between the main axis and branches in solitary plants, whereas in the dense stand it was smaller
on branches. Dry mass was allocated most to leaves in solitary plants and to stems in the dense stand in vegetative growth.
Reproductive allocation was not significantly different. Branch/main stem mass ratio was higher in solitary than dense-stand
plants, and leaf/stem mass ratio higher in branches than in the main axis. Nitrogen use efficiency (NUE) (dry mass growth
per unit N uptake) was higher and light use efficiency (LUE) (dry mass growth per unit light interception) was lower in the
plant grown solitarily than in the dense stand. 相似文献
77.
Jun Wang Hayley Fivecoat Lap Ho Yong Pan Emi Ling Giulio Maria Pasinetti 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(8):1690-1694
Sirt1, a mammalian member of the sirtuin gene family, holds great potential for promoting longevity, preventing against disease and increasing cell survival. For example, studies suggest that the beneficial impact of caloric restriction in promoting longevity and cellular function may be mediated, in part, by Sirt1 through mechanisms involving PGC-1α, which plays important role in the regulation of cellular metabolism and inflammatory and antioxidant responses. Sirt1 may also interfere with mechanisms implicated in pathological disorders. We will present recent evidence indicating that Sirt1 may protect against Alzheimer's disease by interfering with the generation of β-amyloid peptides. We will discuss Sirt1 as a potential novel target, in addition to the development of Sirt1 activators for the prevention and treatment of Alzheimer's disease. 相似文献
78.
Emi Kamiyama Daisuke Nakai Tsuyoshi Mikkaichi Noriko Okudaira Osamu Okazaki 《Life sciences》2010,86(1-2):52-58
AimsThe inhibitory effect of angiotensin II type 1 receptor blockers (ARBs) on P-glycoprotein (P-gp) was examined to evaluate their clinical drug–drug interaction (DDI) potential.Main methodsWe performed an inhibition study on the vectorial transport of digoxin, a typical substrate for P-gp, using a human colonic adenocarcinoma cell line, Caco-2 cells, and verapamil-stimulated ATPase activity using human multidrug resistance 1 (hMDR1)-expressing membrane.Key findingsThe vectorial transport of digoxin was inhibited by candesartan cilexetil, irbesartan and telmisartan with the IC50 values of 14.7, 34.0 and 2.19 µM, respectively. Those values were 7.4–426-fold higher than their theoretical clinical gastrointestinal concentration [I] at doses in clinical DDI studies. Other ARBs failed to show interaction with P-gp.SignificanceIt was demonstrated that candesartan cilexetil, irbesartan and telmisartan had the potential to inhibit the transport of various drugs via P-gp. Telmisartan, which caused an increase in the serum digoxin concentration in humans, had a sufficiently high [I]/IC50 value, suggesting that DDI between digoxin and telmisartan was caused by the inhibition of digoxin efflux via intestinal P-gp. 相似文献
79.
Saito EK Sileo L Green DE Meteyer CU McLaughlin GS Converse KA Docherty DE 《Journal of wildlife diseases》2007,43(2):206-213
West Nile virus (WNV) has affected many thousands of birds since it was first detected in North America in 1999, but the overall impact on wild bird populations is unknown. In mid-August 2002, wildlife rehabilitators and local wildlife officials from multiple states began reporting increasing numbers of sick and dying raptors, mostly red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus). Commonly reported clinical signs were nonspecific and included emaciation, lethargy, weakness, inability to perch, fly or stand, and nonresponse to danger. Raptor carcasses from 12 states were received, and diagnostic evaluation of 56 raptors implicated WNV infection in 40 (71%) of these cases. Histologically, nonsuppurative encephalitis and myocarditis were the salient lesions (79% and 61%, respectively). Other causes of death included lead poisoning, trauma, aspergillosis, and Salmonella spp. and Clostridium spp. infections. The reason(s) for the reported increase in raptor mortality due to WNV in 2002 compared with the previous WNV seasons is unclear, and a better understanding of the epizootiology and pathogenesis of the virus in raptor populations is needed. 相似文献
80.
Nakayama EE Carpentier W Costagliola D Shioda T Iwamoto A Debre P Yoshimura K Autran B Matsushita S Theodorou I 《Immunogenetics》2007,59(6):511-515
Polymorphisms in human genes have been shown to affect the rate of disease progression to acquired immune deficiency syndrome
in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Recently, tripartite motif 5α (TRIM5α) was identified
as a factor that confers resistance to HIV-1 infection in Old World monkey cells. Subsequently, Sawyer et al. (Curr Biol 16:95–100,
2006) reported a single nucleotide polymorphism (H43Y) in the human TRIM5α gene and TRIM5α protein with 43Y was found to lose its ability to restrict HIV-1. In the present study, we reevaluated effects
of this allele on in vitro anti-HIV-1 activity as well as on HIV-1 disease progression in European and Asian cohorts of HIV-1-infected
individuals. Our epidemiological and molecular biological findings clearly indicate H43Y has a very minor effect on anti-HIV-1
activity of TRIM5α, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians. 相似文献