scholarly journals p53-Independent Effects of Mdm2

2014 ◽  
pp. 235-246 ◽  
Author(s):  
Stephen Bohlman ◽  
James J. Manfredi
Keyword(s):  
Independent Effects

Gender-to-ending consistency and agreement processing in Italian: two independent effects?

2013 ◽  
Author(s):  
Sendy Caffarra ◽  
Anna Siyanova-Chanturia ◽  
Francesca Pesciarelli ◽  
Francesca Vespignani ◽  
Cristina Cacciari
Keyword(s):  
Independent Effects

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt
Keyword(s):  
Cell Proliferation ◽  
Cell Metabolism ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nucleic Acid Content ◽  
The Difference ◽  
Independent Effects ◽  
Sites Of Action ◽  
Peripheral Metabolism

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.

Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed

2019 ◽  
Vol 20 (11) ◽  
pp. 1091-1111 ◽  
Author(s):  
Maryam Zanjirband ◽  
Soheila Rahgozar
Keyword(s):  
Clinical Trials ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Tp53 Gene ◽  
Therapeutic Agents ◽  
Negative Regulator ◽  
Mdm2 Protein ◽  
Independent Effects ◽  
Small Hydrophobic ◽  
Targeted Therapeutic

MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphasizes on the p53 function, regulation of p53, targeting of the p53-MDM2 interaction for cancer therapy, and p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with a focus on those entered into clinical trials. Furthermore, the review discusses the gene signatures in order to predict sensitivity to MDM2 antagonists, potential side effects and the reasons for the observed hematotoxicity, mechanisms of resistance to these drugs, their evaluation as monotherapy or in combination with conventional chemotherapy or with other targeted therapeutic agents. Finally, it highlights the certainly intriguing questions and challenges which would be addressed in future studies.

Disentangling adversity timing and type: Contrasting theories in the context of maternal prenatal physical and mental health using latent formative models

2021 ◽  
pp. 1-13
Author(s):  
André Plamondon ◽  
Nicole Racine ◽  
Sheila McDonald ◽  
Suzanne Tough ◽  
Sheri Madigan
Keyword(s):  
Mental Health ◽  
Health Outcomes ◽  
Middle Childhood ◽  
Emotional Abuse ◽  
Physical And Mental Health ◽  
Physical Health Outcomes ◽  
Mental Health Difficulties ◽  
Cumulative Adversity ◽  
Independent Effects ◽  
In Pregnancy

Abstract Research on the effects of adversity has led to mounting interest in examining the differential impact of adversity as a function of its timing and type. The current study examines whether the effects of different types (i.e., physical, sexual, and emotional abuse) and timing (i.e., early, middle childhood, adolescence, or adulthood) of adversity on maternal mental and physical health outcomes in pregnancy, are best accounted for by a cumulative model or independent effects model. Women from a prospective pregnancy cohort (N =3,362) reported retrospectively on their experiences of adversity (i.e., physical, sexual, and emotional abuse) in early childhood (0–5 years], middle childhood (6–12 years], adolescence (13–18 years], and adulthood (19+ years]. Measures of overall health, stress, anxiety, and depression were gathered in pregnancy. Results showed that a cumulative formative latent model was selected as more parsimonious than a direct effects model. Results also supported a model where the strength of the effect of adversity did not vary across abuse timing or type. Thus, cumulative adversity resulted in greater physical and mental health difficulties. In conclusion, cumulative adversity is a more parsimonious predictor of maternal physical and mental health outcomes than adversity at any one specific adversity timing or subtype.

scholarly journals Phylogenetic and metabolic diversity have contrasting effects on the ecological functioning of bacterial communities

2021 ◽  
Vol 97 (3) ◽  
Author(s):  
Constantinos Xenophontos ◽  
Martin Taubert ◽  
W Stanley Harpole ◽  
Kirsten Küsel
Keyword(s):  
Bacterial Communities ◽  
Species Interactions ◽  
Phylogenetic Diversity ◽  
Molecular Mechanisms ◽  
Linear Models ◽  
Theory Development ◽  
Metabolic Diversity ◽  
Community Functioning ◽  
Metabolic Functions ◽  
Independent Effects

ABSTRACT Quantifying the relative contributions of microbial species to ecosystem functioning is challenging, because of the distinct mechanisms associated with microbial phylogenetic and metabolic diversity. We constructed bacterial communities with different diversity traits and employed exoenzyme activities (EEAs) and carbon acquisition potential (CAP) from substrates as proxies of bacterial functioning to test the independent effects of these two aspects of biodiversity. We expected that metabolic diversity, but not phylogenetic diversity would be associated with greater ecological function. Phylogenetically relatedness should intensify species interactions and coexistence, therefore amplifying the influence of metabolic diversity. We examined the effects of each diversity treatment using linear models, while controlling for the other, and found that phylogenetic diversity strongly influenced community functioning, positively and negatively. Metabolic diversity, however, exhibited negative or non-significant relationships with community functioning. When controlling for different substrates, EEAs increased along with phylogenetic diversity but decreased with metabolic diversity. The strength of diversity effects was related to substrate chemistry and the molecular mechanisms associated with each substrate's degradation. EEAs of phylogenetically similar groups were strongly affected by within-genus interactions. These results highlight the unique flexibility of microbial metabolic functions that must be considered in further ecological theory development.

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