Understanding the dimensions of a strong-professional identity: a study of faculty developers in medical education.

BACKGROUND: Faculty developers are regularly involved in training medical educators to enhance their teaching excellence through workshops and other formats. By exemplifying professional and institutional values, faculty developers may profoundly impact how other educators perceive their own professional identity. OBJECTIVE: The objective of this study was to understand how the professional identity of faculty developers is formed. DESIGN: A qualitative approach was used, with a semi-structured interview. The sample consisted of 10 medical educators. A deductive thematic analysis based on Bolivar et al. (2004a) model of professional identity formation for medical educators was carried out. RESULTS: Self-image was impacted favorably through social recognition from students and peers, and the belief of having demonstrated professional competence through job assignments and enrollment in different leadership positions. The social relations to the center or department in which the faculty developer participates were strongly related to job satisfaction. Expectations about the future of the profession included positive attitudes toward change brought by generational differences. Regarding the process of construction of professional identity, life stories and dissimilar professional careers converge in the same educational setting. Faculty developers regularly resort to self-reflection, with a desire to continue learning and developing. They are resilient and purposeful, even in negative experiences that they have faced as identity crises. They share an awareness in building a legacy for the patients, their families, and the community through nurturing new generations of health-care practitioners. CONCLUSIONS: The interviewed faculty developers have a strong-professional identity that is characterized by a stable sense of self, strong behavioral repertoire, and key associations with a community of practice.

The interplay between autophagy and tumorigenesis: exploiting autophagy as a means of anticancer therapy.

In wild-type cells, autophagy represents a tumour-suppressor mechanism, and dysfunction of the autophagy machinery increases genomic instability, DNA damage, oxidative stress and stem/progenitor expansion, which are events associated with cancer onset. Autophagy occurs at a basal level in all cells depending on cell type and cellular microenvironment. However, the role of autophagy in cancer is diverse and can promote different outcomes even in a single tumour. For example, in hypoxic tumour regions, autophagy emerges as a protective mechanism and allows cancer cell survival. By contrast, in cancer cells surrounding the tumour mass, the induction of autophagy by radio- or chemotherapy promotes cell death and significantly reduces the tumour mass. Importantly, inhibition of autophagy compromises tumorigenesis by mechanisms that are not entirely understood. The aim of this review is to explain the apparently contradictory role of autophagy as a mechanism that both promotes and inhibits tumorigenesis using different models. The induction/inhibition of autophagy as a mechanism for cancer treatment is also discussed.

Disruption of the ribosomal P complex leads to stress-induced autophagy.

The human ribosomal P complex, which consists of the acidic ribosomal P proteins RPLP0, RPLP1, and RPLP2 (RPLP proteins), recruits translational factors, facilitating protein synthesis. Recently, we showed that overexpression of RPLP1 immortalizes primary cells and contributes to transformation. Moreover, RPLP proteins are overexpressed in human cancer, with the highest incidence in breast carcinomas. It is thought that disruption of the P complex would directly affect protein synthesis, causing cell growth arrest and eventually apoptosis. Here, we report a distinct mechanism by which cancer cells undergo cell cycle arrest and induced autophagy when RPLP proteins are downregulated. We found that absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. Moreover, ROS generation led to endoplasmic reticulum (ER) stress that involved the EIF2AK3/PERK-EIF2S1/eIF2α-EIF2S2-EIF2S3-ATF4/ATF-4- and ATF6/ATF-6-dependent arms of the unfolded protein response (UPR). RPLP protein-deficient cells treated with autophagy inhibitors experienced apoptotic cell death as an alternative to autophagy. Strikingly, antioxidant treatment prevented UPR activation and autophagy while restoring the proliferative capacity of these cells. Our results indicate that ROS are a critical signal generated by disruption of the P complex that causes a cellular response that follows a sequential order: first ROS, then ER stress/UPR activation, and finally autophagy. Importantly, inhibition of the first step alone is able to restore the proliferative capacity of the cells, preventing UPR activation and autophagy. Overall, our results support a role for autophagy as a survival mechanism in response to stress due to RPLP protein deficiency.

Tissue oxygenation, strength and lactate response to different blood flow restrictive pressures.

This study aimed to determine whether changes in initial restrictive pressures (IRP, tightness of the cuff before inflation with air) affect tissue oxygenation, lactate production and leg strength before, during and after knee extension exercises. The cuff was positioned on the right thigh, and the IRP of either 40-45 or 60-65 mmHg were applied randomly prior to inflating the cuff to the final restrictive pressure (the pressure reached after inflating the cuff with air). Subjects performed four sets (30, 15, 15 and 15 reps) of isotonic knee extensions with 1-min rest between sets. Tissue oxygenation and blood lactate levels were assessed prior to, during and after exercise, and leg strength was assessed pre- and postexercise. There were significant condition by time interactions (P<0·01) and main effects for both condition (P<0·01) and time (P<0·01) for tissue oxygenation, deoxyhaemoglobin, total haemoglobin. Significant main effects were detected for both condition (P<0·01) and time (P<0·01) for leg strength values. There was only a significant time main effect for lactate concentrations. This study is the first to show that a higher IRP had a significant impact on percent tissue oxygenation, leg strength and deoxygenated haemoglobin accumulation during exercise.

miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-α, CCNJ, and MEGF9.

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-α, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-α, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-α was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-α, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-α, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer.

Arsenic mobility controlled by solid calcium arsenates: a case study in Mexico showcasing a potentially widespread environmental problem.

An As-contaminated perched aquifer under an urban area affected by mining was studied over a year to determine the contamination source species and the mechanism of As mobilization. Results show that the dissolution of calcium arsenates in residues disposed on an inactive smelter has caused high levels of As pollution in the adjoining downgradient 6-km perched aquifer, reaching up to 158 mg/L of dissolved As, and releasing a total of ca. 7.5 tons of As in a year. Furthermore, free calcium ion availability was found to control As mobility in the aquifer through the diagenetic precipitation of calcium arsenates (Ca5H2(AsO4)4·cH2O) preventing further mobilization of As. Results shown here represent a model for understanding a highly underreported mechanism of retention of arsenate species likely to dominate in calcium-rich environments, such as those in calcareous sediments and soils, where the commonly reported mechanism of adsorption to iron(III) oxyhydroxides is not the dominant process.

Stem cell microRNAs in senescence and immortalization: novel players in cancer therapy.

The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein-coding RNAs that regulate gene expression. They are involved in important homeostatic processes, such as cellular proliferation, cell death and development, and affect many diseases, including cancer. High-throughput screenings based on microRNAs related to senescence/immortalization are potential tools for identifying novel proliferative microRNAs that might be involved in carcinogenesis. Recently, a subgroup of highly proliferative microRNAs, which belong to a cluster expressed exclusively in embryonic stem cells and their malignant derivatives (embryonic carcinoma cells), was revealed to play a role in senescence bypass, thereby providing immortalization to human cells. This finding supports the cancer stem cell theory and the relevance of microRNAs in human tumors. This article recapitulates the role of microRNAs that are associated with stem cell properties and their possible link in common pathways related to immortalization and cancer. Ultimately, cancer therapy that is based on the induction of a senescence response is proposed to be highly associated with the loss of stemness properties. Thus, it would be possible to "kill two birds with one stone": along with the inhibition of stemness properties in cancer stem cells, the senescence response could be induced to destroy the cancer stem cell population within a tumor.