AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer

A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of the constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective FASN inhibition antagonizes CRPC growth through metabolic reprogramming and results in reduced protein expression and transcriptional activity of both full-length AR (AR-FL) and AR-V7. Activation of the reticulum endoplasmic stress response resulting in reduced protein synthesis was involved in IPI-9119-mediated inhibition of the AR pathway. In vivo, IPI-9119 reduced growth of AR-V7-driven CRPC xenografts and human mCRPC-derived organoids and enhanced the efficacy of enzalutamide in CRPC cells. In human mCRPC, both FASN and AR-FL were detected in 87% of metastases. AR-V7 was found in 39% of bone metastases and consistently coexpressed with FASN. In patients treated with enzalutamide and/or abiraterone FASN/AR-V7 double-positive metastases were found in 77% of cases. These findings provide a compelling rationale for the use of FASN inhibitors in mCRPCs, including those overexpressing AR-V7.Giorgia Zadra, Caroline F. Ribeiro, Paolo Chetta, Yeung Ho, Stefano Cacciatore ... Lisa M. Butler ... et al

Preference for Multiple Choice and Constructed Response Exams for Engineering Students with and without Learning Difficulties

Problem solving is a fundamental part of engineering education. The aim of this study is to compare engineering students’ perceptions and attitudes towards problem-based multiple-choice and constructed response exams. Data were collected from 105 students, 18 of them reported to face some learning difficulty. All the students had an experience of four or more problem-based multiple-choice exams. Overall, students showed a preference towards multiple-choice exams although they did not consider them to be fairer, easier or less anxiety invoking. Students facing learning difficulties struggle with written exams independently of their format and their preferences towards the two examination formats are influenced by the specificity of their learning difficulties. The degree to which each exam format allows students to show what they have learned and be rewarded for partial knowledge, is also discussed. The replies to this question were influenced by students’ preference towards each examination format. Copyright © 2021 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserve

Acceptance of Distance Learning during the COVID-19 Movement Restrictions: Does the Year of Studies Matter?

This study presents the attitudes and perceptions of a sample of undergraduate students on remote teaching after face-to-face teaching was discontinued due to COVID-19 measures. The students expressed a preference for face-to-face teaching and reported higher cognitive engagement, learning and understanding associated with this teaching modality. Important differences were recorded on students’ replies depending on the year of studies. Overall, students who are at the first years of their studies appear to perceive the present situation of remote teaching, as more dissatisfactory compared to the more senior students. Copyright © 2021 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserve

Problem-Based Multiple Response Exams for Students with and Without Learning Difficulties

Objective computer-assisted examinations (CAA) are considered a preferable option compared to constructed response (CR) ones because marking is done automatically without the intervention of the examiner. This publication compares the attitudes and perceptions of a sample of engineering students towards a specific objective examination format designed to assess the students’ proficiency to solve electronics problems. Data were collected using a 15-item questionnaire which included a free text question. Overall the students expressed a preference for the objective-type examination format. The students who self-reported to face learning difficulties (LD) were equally divided between the two examination formats. Their examination format preference was determined by the details of their learning difficulties, indicating that none of the two assessment formats effectively solves the assessment question for these students. For the rest of the respondents, examination format preference was accompanied by opposing views regarding answering by guessing, having the opportunity to express their views, selecting instead of constructing an answer, having the opportunity to demonstrate their knowledge, and having control of the exam answers. © 2022, Springer Nature Switzerland AG

A method for the calculation the activation energies of thermally stimulated depolarization current peaks: Application in polyvinylidene fluoride/graphene nanocomposites

A simple method is presented for the calculation of the activation energies of first order peaks of Thermally Stimulated Depolarization Current (TSDC). Three equations are derived, which relate the activation energy of the relaxation process, to three characteristic temperatures of the TSDC thermographs, which correspond to the peak temperature TM, and the half of the peak current temperatures T1, T2 (T1<T2). Each equation gives an expression of the activation energy as a function of two out of the three characteristic temperatures of the TSDC peak, assuming typical values of activation energy in the range 0.2–2.0 eV. The proposed equations were compared with other methods based on the same characteristic temperatures, in pristine PVDF and PVDF with 1wt% graphene samples at a temperature range where the MWS relaxation takes place. In PVDF-graphene samples, the MWS peak was found to consist of two overlapping mechanisms. © 2021 Elsevier B.V