Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and ...oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.
The mechanistic target of rapamycin complex 1 (mTORC1) stimulates a coordinated anabolic program in response to growth-promoting signals. Paradoxically, recent studies indicate that mTORC1 can ...activate the transcription factor ATF4 through mechanisms distinct from its canonical induction by the integrated stress response (ISR). However, its broader roles as a downstream target of mTORC1 are unknown. Therefore, we directly compared ATF4-dependent transcriptional changes induced upon insulin-stimulated mTORC1 signaling to those activated by the ISR. In multiple mouse embryo fibroblast and human cancer cell lines, the mTORC1-ATF4 pathway stimulated expression of only a subset of the ATF4 target genes induced by the ISR, including genes involved in amino acid uptake, synthesis, and tRNA charging. We demonstrate that ATF4 is a metabolic effector of mTORC1 involved in both its established role in promoting protein synthesis and in a previously unappreciated function for mTORC1 in stimulating cellular cystine uptake and glutathione synthesis.
This article reviews literature focused on diversity and inclusion in human resource development (HRD) journals. A focused analysis of articles published from 2010 to the present reveals shifting ...conceptualizations of diversity inside and outside the Academy of Human Resource Development. This integrative review summarizes the types of diversity articles presented and captures the frameworks, approaches, and foci of current diversity and inclusion research. The influence of social cognitive psychology becomes apparent, as the awareness of multiple identities and experiences becomes central to teaching and learning how to value diversity. The findings also suggest that research and practice in the context of marginalized communities, and non-Western countries, is crucial to broadening the scope of diversity and inclusion in both dominant and nondominant cultures. After categorizing the articles, a discussion of recent theories, pedagogy, and utility follows. The review concludes with a discussion of practice and research implications.
The Problem
The current pipeline supplying qualified and competent leaders to the upper ranks of higher education appears to prelimit the number of Black males who reach executive status. Even though ...many universities and colleges remain resolute in increasing diversity, social, and structural barriers block access and restrict executive development. This study focuses on the leadership and career advancement of Black male executive leaders in predominantly White institutions (PWI’s) of higher education.
The Solution
This qualitative, phenomenological examination of the lived experiences of 10 Black male, executive leaders in predominantly White institutions of higher education describes what it is like for them to persist in their leadership roles despite negative experiences that are related to their social identity. The findings reveal how their existence in racialized environments has impacted their leadership approach and the trajectory of their careers.
The Stakeholders
The stakeholders are Black academics seeking or holding executive leadership roles in higher education; HRD scholars and practitioners.
There are two dichotomous rationales for valuing diversity in organizational contexts: the business case and the social justice case. Arguments for the business case for diversity and the social ...justice case are both supported by valuing philosophies. However, lacking in either of these philosophies is a human relations component that recognizes the role of relationships in achieving the intended goals. In this article, we propose that reconciling the tensions between the business case and the social justice case is contingent upon adopting an organizational strategy that includes a human relations valuing philosophy. The organizational strategy suggested reaffirms a strategic role of human resource development.
Outbreaks of cyclosporiasis, an enteric illness caused by the parasite
, have been associated with consumption of various types of fresh produce. Although a method is in use for genotyping
from ...clinical specimens, the very low abundance of
in food and environmental samples presents a greater challenge. To complement epidemiological investigations, a molecular surveillance tool is needed for use in genetic linkage of food vehicles to cyclosporiasis illnesses, estimation of the scope of outbreaks or clusters of illness, and determination of geographical areas involved. We developed a targeted amplicon sequencing (TAS) assay that incorporates a further enrichment step to gain the requisite sensitivity for genotyping
contaminating fresh produce samples. The TAS assay targets 52 loci, 49 of which are located in the nuclear genome, and encompasses 396 currently known SNP sites. The performance of the TAS assay was evaluated using lettuce, basil, cilantro, salad mix, and blackberries inoculated with
oocysts. A minimum of 24 markers were haplotyped even at low contamination levels of 10 oocysts in 25 g leafy greens. The artificially contaminated fresh produce samples were included in a genetic distance analysis based on haplotype presence/absence with publicly available
whole genome sequence assemblies. Oocysts from two different sources were used for inoculation, and samples receiving the same oocyst preparation clustered together, but separately from the other group, demonstrating the utility of the assay for genetically linking samples. Clinical fecal samples with low parasite loads were also successfully genotyped. This work represents a significant advance in the ability to genotype
contaminating fresh produce along with greatly expanding the genomic diversity included for genetic clustering of clinical specimens.
Purpose
Disruption due to a crisis or disaster is a constant threat for the tourism industry, unfortunately the frameworks designed to prepare leaders for these events are inadequate. Most frameworks ...are designed to assess and enhance resilience and recovery and minimally prepare leaders for the complexities that emerge before, during and after these events. The purpose of this paper is to offer a leadership development framework that integrates context, competence and a complexity mindset.
Design/methodology/approach
This general review examines the literature focused on crises and disasters in the tourism industry for the purpose of understanding the circumstances surrounding several kinds of disruptive events, the competencies needed to address them. It also explores the usefulness of three forms of leadership development inputs. The result is a framework that builds capacity while ensuring organizational alignment.
Findings
The preparation of tourism industry leaders who address implications of crises and disaster should involve an understanding of the crisis processes and factors that can be known, and the development of a mindset that allows the leader to address those factors which cannot be known beforehand.
Originality/value
This paper offers a framework for tourism leaders and developers that moves beyond static and linear approaches to crisis and disaster training. It encourages the acquisition of contextual knowledge and adaptive processes through leadership-focused education, exposure to leaders and experiences.
The tuberous sclerosis complex (TSC) 1 and 2 proteins associate with TBC1D7 to form the TSC complex, which is an essential suppressor of mTOR complex 1 (mTORC1), a ubiquitous driver of cell and ...tissue growth. Loss-of-function mutations in TSC1 or TSC2, but not TBC1D7, give rise to TSC, a pleiotropic disorder with aberrant activation of mTORC1 in various tissues. Here, we characterize mice with genetic deletion of Tbc1d7, which are viable with normal growth and development. Consistent with partial loss of function of the TSC complex, Tbc1d7 knockout (KO) mice display variable increases in tissue mTORC1 signaling with increased muscle fiber size but with strength and motor defects. Their most pronounced phenotype is brain overgrowth due to thickening of the cerebral cortex, with enhanced neuron-intrinsic mTORC1 signaling and growth. Thus, TBC1D7 is required for full TSC complex function in tissues, and the brain is particularly sensitive to its growth-suppressing activities.
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•A mouse knockout of Tbc1d7 encoding a core component of the TSC complex is presented•Tbc1d7 KO mice display increased tissue mTORC1 signaling but normal development•Tbc1d7 KO mice exhibit brain overgrowth with cortical thickening•Tbc1d7 KO neurons display mTORC1-dependent increases in growth and defects in polarity
Schrötter et al. describe a mouse knockout model of TBC1D7, a core component of the tuberous sclerosis complex (TSC) protein complex, which serves as a central brake on mTORC1 signaling and cell and tissue growth. Tbc1d7 KO mice exhibit brain overgrowth associated with an mTORC1-dependent increase in neuronal cell size.
Purpose
– The purpose of this paper is to understand the factors and conditions that influence national human resource development (NHRD) in Brazil. In this paper, the transitioning nature of the ...political, economic, social and educational conditions; the current challenges and trends that may impact NHRD; and the current status of NHRD research in Brazil are examined.
Design/methodology/approach
– A search of the research literature focused on the political, economic, cultural, social and educational environment and the research associated with NHRD in Brazil was conducted. After searching several databases, including Academic Search Complete, Google Scholar, ERIC and EBSCO, several articles were selected and analyzed based on the depth of description of the conditions and research.
Findings
– Among the factors discovered, race, gender and educational equality are still concerns. The complex nature of the relationship between the Brazilian Government, its people and organizations, as well as the efforts of Brazil’s multinational and indigenous organizations to address their national development needs, are also presented.
Originality/value
– Brazil is currently and projected to be a long-term player in the global economy; however, it struggles to cope with conditions incongruent to the country’s long-term success. This paper frames the conditions and suggests ways of moving forward through human resource development practice, policy and research in Brazil.
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether ...changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.
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