MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation

One of the major health concerns on long‐duration space missions will be radiation exposure to the astronauts. Outside the earth’s magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel. The hematopoietic system is one of the most radiation‐sensitive organ systems, and is highly dependent on functional DNA repair pathways for survival. Recent results from our group have demonstrated an acquired deficiency in mismatch repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional loss of the MLH1 protein, suggesting an additional risk to astronauts who may have significant numbers of MMR deficient HSCs at the time of space travel. In the present study, we investigated the effects gamma radiation, proton radiation, and 56Fe radiation on HSC function in Mlh1+/+ and Mlh1‐/‐ marrow from mice in a variety of assays and have determined that while cosmic radiation is a major risk to the hematopoietic system, there is no dependence on MMR capacity. Stem Cells Translational Medicine 2018;7:513–520The hematopoietic system is essential for life, and normally has the capacity to sustain function for the duration of our lifetimes in spite of natural declination, which is associated with loss of DNA repair (including as DNA mismatch repair). Astronauts are exposed to ionizing radiation sources that are not commonly found on earth (such as HZE ions) and thus may display unforseen risks that need accounting in NASA risk models.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145333/1/sct312310.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145333/2/sct312310_am.pd

Corporate Social Responsibility in Supply Chains of Small and Medium‐Sized Enterprises

Research has shown that implementation of corporate social responsibility (CSR) practice represents a considerable challenge for small and medium-sized enterprises (SMEs). This research conceptualises the dimensions and contingencies of CSR in SMEs’ supply chains. Drawing on institutional theory and stakeholder theory, we investigates the degree of importance and implementation of CSR practices in SMEs. A large-scale questionnaire survey with SMEs in manufacturing sectors and panel discussions were conducted in South Korea. The findings indicate that SMEs tend to focus on explicit CSR practices that can be easily identified by their customers. Consistent with this, stakeholder and institutional pressures were valid in the performance of CSR practices, but largely biased to customers, government and regulatory pressures. Based on institutional theory and stakeholder theory as overarching theoretical lenses, this research contributes to offer a fuller understanding of dimensions of CSR practices in the supply chains from a SME perspective

HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism

Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxiainducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A (CPT1A), as a direct HIF target gene. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. Droplet formation occurs independent of lipid source, but only when CPT1A is repressed. Functionally, repression of CPT1A is critical for tumor formation, as elevated CPT1A expression limits tumor growth. In human tumors, CPT1A expression and activity are decreased versus normal kidney; and poor patient outcome associates with lower expression of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty acid metabolism as essential for ccRCC tumorigenesis

On the effectiveness of private transnational governance regimes - evaluating corporate sustainability reporting according to the Global Reporting Initiative

The increasing involvement of multinational enterprises (MNEs) in global governance has been both applauded for its potential to make governance more effective and criticized for lacking democratic legitimization. Hence we investigate the effectiveness of one transnational governance regime, corporate sustainability reporting according to the Global Reporting Initiative (GRI). We found that the GRI has been successful in terms of output effectiveness by promoting the dissemination of sustainability reporting, in particular among Asian and South American companies. However, the outcome effectiveness of the GRI is limited as reporting showed a rather uniform content across countries and sectors which does not reflect materiality considerations. As GRI reporting does not seem to have facilitated greater company–stakeholder interaction, its impact effectiveness is likely to be limited too