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121.
Aya Masaoka Natalie R. Gassman Julie K. Horton Padmini S. Kedar Kristine L. Witt Cheryl A. Hobbs Grace E. Kissling Keizo Tano Kenjiro Asagoshi Samuel H. Wilson 《PloS one》2013,8(6)
The breast cancer 1 (BRCA1) protein is a tumor suppressor playing roles in DNA repair and cell cycle regulation. Studies of DNA repair functions of BRCA1 have focused on double-strand break (DSB) repair pathways and have recently included base excision repair (BER). However, the function of BRCA1 in BER is not well defined. Here, we examined a BRCA1 role in BER, first in relation to alkylating agent (MMS) treatment of cells and the BER enzyme DNA polymerase β (pol β). MMS treatment of BRCA1 negative human ovarian and chicken DT40 cells revealed hypersensitivity, and the combined gene deletion of BRCA1 and pol β in DT40 cells was consistent with these factors acting in the same repair pathway, possibly BER. Using cell extracts and purified proteins, BRCA1 and pol β were found to interact in immunoprecipitation assays, yet in vivo and in vitro assays for a BER role of BRCA1 were negative. An alternate approach with the human cells of immunofluorescence imaging and laser-induced DNA damage revealed negligible BRCA1 recruitment during the first 60 s after irradiation, the period typical of recruitment of pol β and other BER factors. Instead, 15 min after irradiation, BRCA1 recruitment was strong and there was γ-H2AX co-localization, consistent with DSBs and repair. The rapid recruitment of pol β was similar in BRCA1 positive and negative cells. However, a fraction of pol β initially recruited remained associated with damage sites much longer in BRCA1 positive than negative cells. Interestingly, pol β expression was required for BRCA1 recruitment, suggesting a partnership between these repair factors in DSB repair. 相似文献
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123.
Objective
To investigate factors associated with engagement of U.S. Federal Health Agencies via Twitter. Our specific goals are to study factors related to a) numbers of retweets, b) time between the agency tweet and first retweet and c) time between the agency tweet and last retweet.Methods
We collect 164,104 tweets from 25 Federal Health Agencies and their 130 accounts. We use negative binomial hurdle regression models and Cox proportional hazards models to explore the influence of 26 factors on agency engagement. Account features include network centrality, tweet count, numbers of friends, followers, and favorites. Tweet features include age, the use of hashtags, user-mentions, URLs, sentiment measured using Sentistrength, and tweet content represented by fifteen semantic groups.Results
A third of the tweets (53,556) had zero retweets. Less than 1% (613) had more than 100 retweets (mean = 284). The hurdle analysis shows that hashtags, URLs and user-mentions are positively associated with retweets; sentiment has no association with retweets; and tweet count has a negative association with retweets. Almost all semantic groups, except for geographic areas, occupations and organizations, are positively associated with retweeting. The survival analyses indicate that engagement is positively associated with tweet age and the follower count.Conclusions
Some of the factors associated with higher levels of Twitter engagement cannot be changed by the agencies, but others can be modified (e.g., use of hashtags, URLs). Our findings provide the background for future controlled experiments to increase public health engagement via Twitter. 相似文献124.
María Hernndez Mesa Jonas van den Brink William E. Louch Kimberly J. McCabe Padmini Rangamani 《PLoS computational biology》2022,18(6)
Super-resolution imaging techniques have provided a better understanding of the relationship between the nanoscale organization and function of ryanodine receptors (RyRs) in cardiomyocytes. Recent data have indicated that this relationship is disrupted in heart failure (HF), as RyRs are dispersed into smaller and more numerous clusters. However, RyRs are also hyperphosphorylated in this condition, and this is reported to occur preferentially within the cluster centre. Thus, the combined impact of RyR relocalization and sensitization on Ca2+ spark generation in failing cardiomyocytes is likely complex and these observations suggest that both the nanoscale organization of RyRs and the pattern of phosphorylated RyRs within clusters could be critical determinants of Ca2+ spark dynamics. To test this hypothesis, we used computational modeling to quantify the relationships between RyR cluster geometry, phosphorylation patterns, and sarcoplasmic reticulum (SR) Ca2+ release. We found that RyR cluster disruption results in a decrease in spark fidelity and longer sparks with a lower amplitude. Phosphorylation of some RyRs within the cluster can play a compensatory role, recovering healthy spark dynamics. Interestingly, our model predicts that such compensation is critically dependent on the phosphorylation pattern, as phosphorylation localized within the cluster center resulted in longer Ca2+ sparks and higher spark fidelity compared to a uniformly distributed phosphorylation pattern. Our results strongly suggest that both the phosphorylation pattern and nanoscale RyR reorganization are critical determinants of Ca2+ dynamics in HF. 相似文献
125.
Sahai A Malladi P Pan X Paul R Melin-Aldana H Green RM Whitington PF 《American journal of physiology. Gastrointestinal and liver physiology》2004,287(5):G1035-G1043
Obesity and type 2 diabetes are associated with nonalcoholic steatohepatitis (NASH), but an obese/diabetic animal model that mimics human NASH remains undefined. We examined the induction of steatohepatitis and liver fibrosis in obese and type 2 diabetic db/db mice in a nutritional model of NASH and determined the relationship of the expressions of osteopontin (OPN) and leptin receptors to the pathogenesis of NASH. db/db mice and the corresponding lean and nondiabetic db/m mice were fed a diet deficient in methionine and choline (MCD diet) or control diet for 4 wk. Leptin-deficient obese and diabetic ob/ob mice fed similar diets were used for comparison. MCD diet-fed db/db mice exhibited significantly greater histological inflammation and higher serum alanine aminotransferase levels than db/m and ob/ob mice. Trichrome staining showed marked pericellular fibrosis in MCD diet-fed db/db mice but no significant fibrosis in db/m or ob/ob mice. Collagen I mRNA expression was increased 10-fold in db/db mice, 4-fold in db/m mice, and was unchanged in ob/ob mice. mRNA expressions of OPN, TNF-alpha, TGF-beta, and short-form leptin receptors (Ob-Ra) were significantly increased in db/db mice compared with db/m or ob/ob mice. Parallel increases in OPN and Ob-Ra protein levels were observed in db/db mice. Cultured hepatocytes expressed only Ob-Ra, and leptin stimulated OPN mRNA and protein expression in these cells. In conclusion, our results demonstrate the development of an obese/diabetic experimental model for NASH in db/db mice and suggest an important role for Ob-Ra and OPN in the pathogenesis of NASH. 相似文献
126.
V. Uma Maheshwari Nallal R. Padmini B. Ravindran Soon Woong Chang R. Radhakrishnan Hesham Saleh M. Almoallim Sulaiman Ali Alharbi M. Razia 《Saudi Journal of Biological Sciences》2021,28(2):1246-1256
Candida infections and related mortality have become a challenge to global health. Nontoxic and natural bioactive compounds from plants are regarded as promising candidates to inhibit these multidrug resistant strains. In the present study, in vitro assays and in silico molecular docking approach was combined to evaluate the inhibitory effect of crude extracts from Allium ampeloprasum and its variety A. porrum on Candida pathogens. Phytochemical screening revealed the presence of phenolic acids and flavonoids in higher quantity. Spectral studies of the extracts support the presence of phenols, flavonoids and organosulfur compounds. Aqueous extract of A. ampeloprasum showed a total antioxidant capacity of 68 ± 1.7 mg AAE/ g and an IC50 value of 0.88 ± 2.1 mg/ml was obtained for DPPH radicals scavenging assay. C. albicans were highly susceptible (19.9 ± 1.1 mm) when treated with aqueous A. ampeloprasum extract. Minimum inhibitory concentrations were within the range of 19–40 μg/ml and the results were significant (p ≤ 0.05). In silico molecular docking studies demonstrated that bioactive phytocompounds of A. ampeloprasum and A. porrum efficiently interacted with the active site of Secreted aspartyl proteinase 2 enzyme that is responsible for the virulence of pathogenic yeasts. Rosmarinic acid and Myricetin exhibited low binding energies and higher number of hydrogen bond interactions with the protein target. Thus the study concludes that A. ampeloprasum and A. porrum that remain as underutilized vegetables in the Allium genus are potential anti-candida agents and their pharmacologically active compounds must be considered as competent candidates for drug discovery. 相似文献
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128.
Macrophages from lepromatous leprosy patients showed poor adherence toMycobacterium leprae. The phagocytic activity of the macrophages was not correlated to the influence on the adherence ability. Based on the phagocytic
behaviour of macrophages from normal individuals and from lepromatous leprosy, patients as well as the action of neuraminidase
in reversing the extent of adherence, it is suggested that macrophages from lepromatous leprosy patients differ from those
from normal individuals in regard to their surface properties. There was no relationship between the degree of adherence and
the concentration of Fc receptors of the macrophages. It was also shown that an extract of lysed macrophages from lepromatous
leprosy patient was able to reduce the adherence ofMycobacterium leprae to normal macrophages. This study shows that adherence is a good indicator of the surface property of macrophages which in
turn could play an important role in the cell mediated immunity of the patient. The observations suggest altered macrophage
membrane structure in the long term-treated, otherwise normal, lepromatous leprosy patients. 相似文献
129.
130.
Activities of cytidine 5′-diphosphate-choline glycerol choline phosphotransferase and uridine 5′-diphosphate galactose-ceramide
galactosyltransferase were determined in isolated myelin in different brain regions of control, and rats with restricted food
intake. Kinetic experiments indicated an increase inK
m value of phosphocholinetransferase in brain stem of undernourished rats, without significant change in the specific activity
of this enzyme. Stimulation of this myelin bound enzyme activity was also evident in the animals when myelin was treated with
the detergent: Tween CF. 54. Though specific activities of galactosyl transferase in myelin of undernourished rats were significantly
diminished, theK
m of this enzyme was unaltered. These studies point to an adverse effect of early nutritional stress on the activities of enzymes
bound to myelin membrane which has hitherto been considered metabolically inert. 相似文献