ICM Partners

About: ICM Partners is a based out in . It is known for research contribution in the topics: Population & Breast cancer. The organization has 1311 authors who have published 1521 publications receiving 33745 citations. The organization is also known as: International Creative Management Partners.

Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.

Abstract: Imbalance in the level of the pyrimidine degradation products dihydrouracil and dihydrothymine is associated with cellular transformation and cancer progression. Dihydropyrimidines are degraded by dihydropyrimidinase (DHP), a zinc metalloenzyme that is upregulated in solid tumors but not in the corresponding normal tissues. How dihydropyrimidine metabolites affect cellular phenotypes remains elusive. Here we show that the accumulation of dihydropyrimidines induces the formation of DNA-protein crosslinks (DPCs) and causes DNA replication and transcriptional stress. We used Xenopus egg extracts to recapitulate DNA replication invitro. We found that dihydropyrimidines interfere directly with the replication of both plasmid and chromosomal DNA. Furthermore, we show that the plant flavonoid dihydromyricetin inhibits human DHP activity. Cellular exposure to dihydromyricetin triggered DPCs-dependent DNA replication stress in cancer cells. This study defines dihydropyrimidines as potentially cytotoxic metabolites that may offer an opportunity for therapeutic-targeting of DHP activity in solid tumors.

System for providing auxiliary power

Abstract: A system for providing auxiliary power comprises a primary circuit including a primary pump, an output line for providing primary power, and a return line. An auxiliary circuit includes an auxiliary pump, an output line for providing the auxiliary power and a return line. The auxiliary circuit also includes a valve for controlling fluid flow in the output and return line of the auxiliary circuit. A reservoir is connected to the primary return line and to the auxiliary return line. A controlled leakage apparatus for cooling the auxiliary pump is connected to the auxiliary circuit, the reservoir and the primary circuit, and in response to a predetermined pressure in the primary circuit directs a portion of auxiliary output fluid to the reservoir. Approximately all of the auxiliary output fluid is directed to the auxiliary output line when the primary circuit provides less than the predetermined pressure. The auxiliary circuit includes a drive apparatus connected to a vehicle for operating the auxiliary pump whenever the vehicle is moving.

Prevalence of self‐reported subthreshold phenotypes of major mental disorders and their association with functional impairment, treatment and full‐threshold syndromes in a community‐residing cohort of young adults

Abstract: Aim: Subthreshold syndromes (STS) frequently precede the onset of full-threshold syndromes (FTS) of the corresponding mental disorder (homotypic continuity). This study examines whether subthreshold conditions are comorbid and whether there is heterotypic continuity also between STS and FTS. Methods: Data were extracted from the Brisbane “19Up” cohort study of twins and siblings (N = 1838; 56% female) on individuals who (i) completed self-report ratings of depression-like (DLE), hypomanic-like (HMLE) and psychotic-like experiences (PLE) and (ii) were assessed for mood and psychotic FTS using the Composite International Diagnostic Interview (CIDI). Associations between STS and FTS were estimated using adjusted prevalence ratios (APR) and 95% confidence intervals (CI). Results: STS are prevalent, with 22% reporting DLE, 14% HMLE and 5% PLE; 7% reported >1 STS, with PLE most likely to demonstrate comorbidity. Individuals with DLE were likely to meet CIDI criteria for depression (APR: 3.71, 95% CI: 2.83, 4.89), hypo/mania (APR: 3.62, 95% CI: 2.21, 5.94) and psychotic disorders (APR: 1.74, 95% CI 1.08, 2.83). Individuals with HMLE were likely to meet CIDI criteria for depression (APR: 2.29, 95% CI: 1.58, 3.31) and hypo/mania (APR: 2.51, 95% CI: 1.29, 4.91); those with PLE were likely to meet criteria for hypo/mania (APR: 5.8, 95% CI: 1.90, 17.70) and psychotic disorders (APR: 17.27, 95% CI: 7.54, 39.65). Conclusions: The findings suggest that STS are common among young adults and show heterotypic as well as homotypic continuity with FTS and support the need for more trans-diagnostic research on the evolution of major mental disorders.