Browsing by Subject "mechanisms"

Now showing 1 - 3 of 3
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    Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
    (Oxford, 2022) Tian, Yu; Kim, Andre E.; Bien, Stephanie A.; Lin, Yi; Qu, Conghui; Harrison, Tabitha A.; Carreras-Torres, Robert; Díez-Obrero, Virginia; Dimou, Niki; Drew , David A.; Hidaka, Akihisa; Huyghe, Jeroen R.; Jordahl, Kristina M.; Morrison , John; Murphy, Neil; Obón-Santacana, Mireia; Ulrich, Cornelia M.; Ose, Jennifer; Peoples, Anita R.; Ruiz-Narvaez, Edward A.; Shcherbina, Anna; Stern , Mariana C.; Su, Yu-Ru; van Duijnhoven, Franzel J. B.; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bishop, D. Timothy; Brenner, Hermann; Buchanan, Daniel D.; Chan, Andrew T.; Figueiredo, Jane C.; Gallinger, Steven; Gruber, Stephen B.; Harlid, Sophia; Hoffmeister, Michael; Jenkins, Mark A.; Joshi, Amit D.; Keku, Temitope O.; Larsson, Susanna C.; Marchand, Loic Le; Li, Li; Giles, Graham G.; Milne, Roger L.; Nan, Hongmei; Nassir, Rami; Ogino, Shuji; Budiarto, Arif; Platz, Elizabeth A.; Potter, John D.; Prentice, Ross L.; Rennert, Gad; Sakoda, Lori C.; Schoen, Robert E.; Slattery, Martha L.; Thibodeau, Stephen N.; Van Guelpen, Bethany; Visvanathan, Kala; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Campbell, Peter T.; Casey, Graham; Conti, David V.; Gunter, Marc J.; Kundaje, Anshul; Lewinger, Juan Pablo; Moreno, Victor; Newcomb, Polly A.; Pardamean, Bens; Thomas, Duncan C.; Tsilidis, Konstantinos K.; Peters, Ulrike; Gauderman, W. James; Hsu, Li; Chang-Claude, Jenny; Community and Global Health, Richard M. Fairbanks School of Public Health
    Background: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10−4). Conclusion: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
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    A Security Analysis of Smartphones
    (2011-08) Verma, Ishita; King, Brian; Rizkalla, Maher E.; Lee, Jaehwan (John)
    This work analyzes and discusses the current security environment of today's (and future) smartphones, and proposes a security model which will reduce smartphone vulnerabilities, preserving privacy, integrity and availability of smartphone native applications to authorized parties. For this purpose, we begin with an overlook of current smartphone security standards, and explore the threats, vulnerabilities and attacks on them, that have been uncovered so far with existing popular smartphones. We also look ahead at the future uses of the smartphones, and the security threats that these newer applications would introduce. We use this knowledge to construct a mathematical model, which gives way to policies that should be followed to secure the smartphone under the model. We finally discuss existing and proposed security mechanisms that can be incorporated in the smartphone architecture to meet the set policies, and thus the set security standards.
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    Transcriptome Profiling of the Hippocampal Seizure Network Implicates a Role for Wnt Signaling during Epileptogenesis in a Mouse Model of Temporal Lobe Epilepsy
    (MDPI, 2022-10) Mardones, Muriel D.; Gupta, Kunal; Neurological Surgery, School of Medicine
    Mesial temporal lobe epilepsy (mTLE) is a life-threatening condition characterized by recurrent hippocampal seizures. mTLE can develop after exposure to risk factors such as febrile seizure, trauma, and infection. Within the latent period between exposure and onset of epilepsy, pathological remodeling events occur that contribute to epileptogenesis. The molecular mechanisms responsible are currently unclear. We used the mouse intrahippocampal kainite model of mTLE to investigate transcriptional dysregulation in the ipsilateral and contralateral dentate gyrus (DG), representing the epileptogenic zone (EZ) and peri-ictal zone (PIZ). DG were analyzed after 3, 7, and 14 days by RNA sequencing. In both the EZ and PIZ, transcriptional dysregulation was dynamic over the epileptogenic period with early expression of genes representing cell signaling, migration, and proliferation. Canonical Wnt signaling was upregulated in the EZ and PIZ at 3 days. Expression of inflammatory genes differed between the EZ and PIZ, with early expression after 3 days in the PIZ and delayed expression after 7–14 days in the EZ. This suggests that critical gene changes occur early in the hippocampal seizure network and that Wnt signaling may play a role within the latent epileptogenic period. These findings may help to identify novel therapeutic targets that could prevent epileptogenesis.