Dissection of PIM serine/threonine kinases in FLT3-ITD–induced leukemogenesis reveals PIM1 as regulator of CXCL12–CXCR4-mediated homing and migration

FLT3-ITD–mediated leukemogenesis is associated with increased expression of oncogenic PIM serine/threonine kinases. To dissect their role in FLT3-ITD–mediated transformation, we performed bone marrow reconstitution assays. Unexpectedly, FLT3-ITD cells deficient for PIM1 failed to reconstitute lethally irradiated recipients, whereas lack of PIM2 induction did not interfere with FLT3-ITD–induced disease. PIM1-deficient bone marrow showed defects in homing and migration and displayed decreased surface CXCR4 expression and impaired CXCL12–CXCR4 signaling. Through small interfering RNA–mediated knockdown, chemical inhibition, expression of a dominant-negative mutant, and/or reexpression in knockout cells, we found PIM1 activity to be essential for proper CXCR4 surface expression and migration of cells toward a CXCL12 gradient. Purified PIM1 led to the phosphorylation of serine 339 in the CXCR4 intracellular domain in vitro, a site known to be essential for normal receptor recycling. In primary leukemic blasts, high levels of surface CXCR4 were associated with increased PIM1 expression, and this could be significantly reduced by a small molecule PIM inhibitor in some patients. Our data suggest that PIM1 activity is important for homing and migration of hematopoietic cells through modification of CXCR4. Because CXCR4 also regulates homing and maintenance of cancer stem cells, PIM1 inhibitors may exert their antitumor effects in part by interfering with interactions with the microenvironment

Banks' risk assessment of Swedish SMEs

Building on the literatures on asymmetric information and risk taking, this paper applies conjoint experiments to investigate lending officers' probabilities of supporting credit to established or existing SMEs. Using a sample of 114 Swedish lending officers, we test hypotheses concerning how information on the borrower's ability to repay the loan; alignment of risk preferences; and risk sharing affect their willingness to grant credit. Results suggest that features that reduce the risk to the bank and shift the risk to the borrower have the largest impact. The paper highlights the interaction between factors that influence the credit decision. Implications for SMEs, banks and research are discussed

Religiosity and corporate financial reporting: evidence from a European country

Using a sample of Portuguese privately-held firms, I examine the association between religiosity and financial reporting quality. The results suggest that firms headquartered in Portuguese areas with strong religious adherence and in the core area of the Portuguese religious cult (the district where the Fátima Sanctuary is located) generally experience lower incidence of earnings management. I provide further evidence that the results are robust to alternative measures of religiosity, and that are not driven by firms headquartered in rural areas. I also conclude that religious social norms, together with other forms of external financial monitoring, represent a mechanism for reducing costly agency conflicts. While the religious practice declined in the last decades in Portugal, I provide evidence that, even in a such context, religiosity is associated with reduced acceptance of unethical business practices, in particular, with reduced acceptance of aggressive accounting practices.I thank participants of the Second Paris Financial Management Conference (PFMC, 2014) and the 3RD Workshop on Business Ethics (EIASM, 2015) for their helpful insights.info:eu-repo/semantics/publishedVersio

The European land and inland water CO2, CO, CH4 and N2O balance between 2001 and 2005

Globally, terrestrial ecosystems have absorbed about 30% of anthropogenic greenhouse gas emissions over the period 2000–2007 and inter-hemispheric gradients indicate that a significant fraction of terrestrial carbon sequestration must be north of the Equator. We present a compilation of the CO2, CO, CH4 and N2O balances of Europe following a dual constraint approach in which (1) a landbased balance derived mainly from ecosystem carbon inventories and (2) a land-based balance derived from flux measurements are compared to (3) the atmospheric data-based balance derived from inversions constrained by measurements of atmospheric GHG (greenhouse gas) concentrations. Good agreement between the GHG balances based on fluxes (1294±545 Tg C in CO2-eq yr−1), inventories (1299±200 Tg C in CO2-eq yr−1) and inversions (1210±405 Tg C in CO2-eq yr−1) increases our confidence that the processes underlying the European GHG budget are well understood and reasonably sampled. However, the uncertainty remains large and largely lacks formal estimates. Given that European net land to atmosphere exchanges are determined by a few dominant fluxes, the uncertainty of these key components needs to be formally estimated before efforts could be made to reduce the overall uncertainty. The net land-to-atmosphere flux is a net source for CO2, CO, CH4 and N2O, because the anthropogenic emissions by far exceed the biogenic sink strength. The dual-constraint approach confirmed that the European biogenic sink removes as much as 205±72 Tg C yr−1 from fossil fuel burning from the atmosphere. However, This C is being sequestered in both terrestrial and inland aquatic ecosystems. If the C-cost for ecosystem management is taken into account, the net uptake of ecosystems is estimated to decrease by 45% but still indicates substantial C-sequestration. However, when the balance is extended from CO2 towards the main GHGs, C-uptake by terrestrial and aquatic ecosystems is offset by emissions of non-CO2 GHGs. As such, the European ecosystems are unlikely to contribute to mitigating the effects of climate change.JRC.H.2-Air and Climat

Does facial soft tissue protect against zygomatic fractures?: results of a finite element analysis

Introduction: Zygomatic fractures form a major entity in craniomaxillofacial traumatology. Few studies have dealt with biomechanical basics and none with the role of the facial soft tissues. Therefore this study should investigate, whether facial soft tissue plays a protecting role in lateral midfacial trauma

MAGGnet: an international network to foster mitigation of agricultural greenhouse gases.

Research networks provide a framework for review, synthesis and systematic testing of theories by multiple scientists across international borders critical for addressing global-scale issues. In 2012, a GHG research network referred to as MAGGnet (Managing Agricultural Greenhouse Gases Network) was established within the Croplands Research Group of the Global Research Alliance on Agricultural Greenhouse Gases (GRA). With involvement from 46 alliance member countries, MAGGnet seeks to provide a platform for the inventory and analysis of agricultural GHG mitigation research throughout the world. To date, metadata from 315 experimental studies in 20 countries have been compiled using a standardized spreadsheet. Most studies were completed (74%) and conducted within a 1-3-year duration (68%). Soil carbon and nitrous oxide emissions were measured in over 80% of the studies. Among plant variables, grain yield was assessed across studies most frequently (56%), followed by stover (35%) and root (9%) biomass. MAGGnet has contributed to modeling efforts and has spurred other research groups in the GRA to collect experimental site metadata using an adapted spreadsheet. With continued growth and investment, MAGGnet will leverage limited-resource investments by any one country to produce an inclusive, globally shared meta-database focused on the science of GHG mitigation

Auditor Change Disclosures as Signals of Earnings Management and Risk

Auditor resignations are considered more negative signals than auditor dismissals, but firms’ self-reported distinction between the two may not offer a complete or reliable representation of the nature of the auditor change. 8-K regulations require the disclosure of the adjournment of an audit engagement even if a successor auditor has not yet been named. In compliance with this requirement, some firms file two 8-k’s related to the same auditor change. Exploiting these dual 8-K filings, we create a new measure of the nature of auditor changes and show that 1) both self-reported auditor resignations and dual 8-K filings are related to measures of earnings management and risk; and 2) auditor changes identified as both self-reported resignations and dual 8-K filings are associated with the most negative economic implications (as reflected by the likelihood of financial statement manipulation and bankruptcy risk). We suggest that dual 8-K filings and self-reported resignations are complementary negative signals each capturing unique dimensions of the underlying economic factors