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991.
Hai Hu Hong Li Feng Jiao Ting Han Meng Zhuo Jiujie Cui Yixue Li Liwei Wang 《Journal of hematology & oncology》2017,10(1):158
Background
Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.Methods
We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.Results
We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.Conclusion
Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.992.
Andrew S. Felts Alice L. Rodriguez Ryan D. Morrison Katrina A. Bollinger Daryl F. Venable Anna L. Blobaum Frank W. Byers Analisa Thompson Gray J. Scott Daniels Colleen M. Niswender Carrie K. Jones P. Jeffrey Conn Craig W. Lindsley Kyle A. Emmitte 《Bioorganic & medicinal chemistry letters》2017,27(21):4858-4866
Based on a hypothesis that an intramolecular hydrogen bond was present in our lead series of picolinamide mGlu5 NAMs, we reasoned that an inactive nicotinamide series could be modified through introduction of a fused heterocyclic core to generate potent mGlu5 NAMs. In this Letter, we describe the synthesis and evaluation of compounds that demonstrate the viability of that approach. Selected analogs were profiled in a variety of in vitro assays, and two compounds were evaluated in rat pharmacokinetic studies and a mouse model of obsessive-compulsive disorder. Ancillary pharmacology screening revealed that members of this series exhibited moderate inhibition of the dopamine transporter (DAT), and SAR was developed that expanded the selectivity for mGlu5 versus DAT. 相似文献
993.
Human leptin induces angiogenesis in vivo 总被引:1,自引:0,他引:1
Anagnostoulis S Karayiannakis AJ Lambropoulou M Efthimiadou A Polychronidis A Simopoulos C 《Cytokine》2008,42(3):353-357
Leptin is an adipocyte-produced peptide, which plays a crucial role in the regulation of body weight. There is also evidence that leptin stimulates endothelial cell proliferation and the formation of capillary-like tubes in vitro. The disc angiogenesis system was used to measure the angiogenic effect of leptin in vivo. Discs containing 25, 50, 100 and 250 ng/ml of leptin were implanted subcutaneously in Wistar rats, removed after a growth period of 7 and 14 days, and compared with spontaneous growth controls and with positive controls containing equivalent doses of vascular endothelial growth factor (VEGF). Discs were examined morphologically for stroma and vessel development and by immunohistochemistry for quantitative evaluation of angiogenesis. The specificity of the angiogenic effect of leptin was tested by blocking leptin with a polyclonal anti-leptin antibody. Leptin induced a significant level of angiogenesis in a dose-dependent manner both at 7 and 14 days, with a peak at the dose of 100 ng/ml. The angiogenic activity of leptin was completely abolished by the anti-leptin neutralizing antibody. VEGF also induced significant dose-dependent angiogenesis at the same time points with a peak observed at a concentration of 100 ng/ml. The angiogenic response to leptin was significantly higher at 7 days compared with VEGF but not at the 14-day time point. In conclusion, leptin has a specific angiogenic effect in vivo, which is dose- and time-dependent in a concentration range of 25–250 ng/ml. This effect is equivalent to the angiogenic effect of VEGF but is evident earlier compared with VEGF. 相似文献
994.
Yurixhi Maldonado–López Edelmira Linares–Mazari Robert Bye Guillermo Delgado Francisco J. Espinosa–García 《Economic botany》2008,62(2):161-170
Mexican Arnica Anti–Inflammatory Action: Plant Age Is Correlated with the Concentration of Anti–inflammatory Sesquiterpenes
in the Medicinal Plant
Heterotheca inuloides
Cass. (Asteraceae). Mexican árnica (Heterotheca inuloides Cass.) is a widely used anti–inflammatory medicinal plant in Mexican folk medicine. Although it has been suggested that plant
age, fertilization, and harvesting regime influence the concentration of secondary compounds affecting the therapeutic activity
of the plant, the effect of these variables on the concentration of the Mexican árnica anti–inflammatory compounds was not
known. We quantified anti–inflammatory sesquiterpenes (caryolan–1, 9β–diol, cadalen–15–oic acid, 7–hydroxycadalene, 4–hydroxy–2–isopropyl–4,
7–dimethyl–1[4H] naftalinone, 7–hydroxy–4αH–3, 4–dihydrocadalene, β–caryophyllene, and β–caryophyllene epoxide) in Mexican
árnica plants subjected to fertilization and successive harvests of flowering stems, conditions that mimic the cultivation
and harvesting for árnica in México. Fertilization and successive harvesting and their interaction had no significant effect
on the concentration of anti–inflammatory compounds. However, the concentrations of these compounds were 60% higher in flowering
stems from 15–month–old plants than in those from 4– or 8–month–old plants and was independent of the number of harvests and
fertilization regime applied. 相似文献
995.
Raşit Urhan 《Biologia》2008,63(3):395-401
Two new species of zerconid mites, Zercon uludagicus sp. n. and Z. huseyini sp. n., from Turkey are described and illustrated. The similarities and differences between the species are discussed. The
lists of the taxonomic diagnostic key to adults of Zercon species known from Turkey are also given. 相似文献
996.
997.
Amornrat Chumthong Mana Kanjanamaneesathian Ashara Pengnoo Ruedeekorn Wiwattanapatapee 《World journal of microbiology & biotechnology》2008,24(11):2499-2507
Endospores of B. megaterium were formulated in granule formulations with sodium alginate, lactose and polyvinylpyrrolidone (PVP K-30) by the wet granulation
technique. The granule formulation exhibited good physical characteristics, such as high-water solubility and optimal viscosity,
that would be suitable for spray application. The bacteria remained viable in the dry granule formulation at 109 c.f.u./g after 24 months storage at room temperature. Under laboratory conditions, aqueous solutions of the formulation showed
high activity against mycelial growth of R. solani (99.64 ± 0.14% mycelial inhibition). High viability of the bacterial antagonist on leaf sheath and leaf blade at day 7 after
spraying with the formulation was observed (approximately 106 c.f.u./g of plant). Application of an equivalent number of un-formulated endospores resulted in much loss of the bacterial
endospores even 1 day after application. In a small pilot field study, an aqueous solution of the formulation (3%w/v) applied
by spraying at days 1, 5 and 10 after pathogen inoculation of the rice plants was more effective in suppressing rice sheath
blight disease than one application of a fungicide (Iprodione) at day 1. Additionally, rice plants sprayed with the aqueous
solution of the granule formulation had higher panicle and whole kernel weights than those of fungicide-treated and control
(untreated) plants. 相似文献
998.
Ilhem Messaoudi Miranda Fischer Jessica Warner Buyng Park Julie Mattison Donald K. Ingram Thomas Totonchy Motomi Mori Janko Nikolich‐Žugich 《Aging cell》2008,7(6):908-919
We have recently shown in non‐human primates that caloric restriction (CR) initiated during adulthood can delay T‐cell aging and preserve naïve CD8 and CD4 T cells into advanced age. An important question is whether CR can be initiated at any time in life, and whether age at the time of onset would modulate the beneficial effects of CR. In the current study, we evaluated the impact of CR started before puberty or during advanced age on T‐cell senescence and compared it to the effects of CR started in early adulthood. Our data demonstrate that the beneficial effects of adult‐onset CR on T‐cell aging were lost by both early and late CR onset. In fact, some of our results suggest that inappropriate initiation of CR may be harmful to the maintenance of T‐cell function. This suggests that there may be an optimal window during adulthood where CR can delay immune senescence and improve correlates of immunity in primates. 相似文献
999.
Jacqueline Dosen Marie-Josée Fortin Becky E. Raboy 《International journal of primatology》2017,38(5):962-983
Habitat loss and fragmentation are the leading causes of biodiversity decline world-wide. Animals sensitive to fragmentation experience reduced dispersal, breeding opportunities, and genetic diversity, making them vulnerable to local extinction. Over the last few decades the Atlantic Forest of Brazil has been extremely fragmented, with only 11–16% of forest remaining. The Brazilian government and nongovernmental organizations have taken actions through legislation and conservation initiatives to restore forest. Using computer modeling, we compared how alternative forest restoration strategies could improve functional connectivity for golden-headed lion tamarins (Leontopithecus chrysomelas) in Southern Bahia, Brazil. Strategies differed by restoration configuration, including Within- and Across-Property approaches, and restoration amount (0–20% restoration). Increasing restoration amounts resulted in greater species functional connectivity, and Within-Property and Across-Property strategies both had significantly more connectivity than the Random strategy. We suggest restoration management consider the size and placement of restored forest, and that riparian forest be restored first to create dispersal corridors and reestablish essential ecosystem services. We further suggest the importance of forming canopy bridges across narrow sections of rivers during the early stages of the restoration process to promote increased connectivity of these newly restored areas. Our findings can aid managers and landowners in understanding the implications of different restoration strategies for highly arboreal, matrix-sensitive species. 相似文献
1000.