Inactivation of phosphoenolpyruvate carboxykinase by acetaldehyde.

Preincubation with acetaldehyde at 37°C inactivates rat liver phosphoenolpyruvate carboxykinase. The inactivation is dependent upon the acetaldehyde concentration and the pH and duration of preincubation, and is prevented but not reversed by glutathione. The binding of the substrate ITP appears to be affected in the inactivation process. This effect of acetaldehyde might contribute to inhibition of gluconeogenesis resulting from ethanol metabolism.     

Plant carbon allocation drives turnover of old soil organic matter in permafrost tundra soils

Carbon cycle feedbacks from permafrost ecosystems are expected to accelerate global climate change. Shifts in vegetation productivity and composition in permafrost regions could influence soil organic carbon (SOC) turnover rates via rhizosphere (root zone) priming effects (RPEs), but these processes are not currently accounted for in model predictions. We use a radiocarbon (bomb‐¹⁴C) approach to test for RPEs in two Arctic tall shrubs, alder (Alnus viridis (Chaix) DC.) and birch (Betula glandulosa Michx.), and in ericaceous heath tundra vegetation. We compare surface CO₂ efflux rates and ¹⁴C content between intact vegetation and plots in which below‐ground allocation of recent photosynthate was prevented by trenching and removal of above‐ground biomass. We show, for the first time, that recent photosynthate drives mineralization of older (>50 years old) SOC under birch shrubs and ericaceous heath tundra. By contrast, we find no evidence of RPEs in soils under alder. This is the first direct evidence from permafrost systems that vegetation influences SOC turnover through below‐ground C allocation. The vulnerability of SOC to decomposition in permafrost systems may therefore be directly linked to vegetation change, such that expansion of birch shrubs across the Arctic could increase decomposition of older SOC. Our results suggest that carbon cycle models that do not include RPEs risk underestimating the carbon cycle feedbacks associated with changing conditions in tundra regions.     

The heterodimerization of platelet-derived chemokines

Chemokines encompass a large family of proteins that act as chemoattractants and are involved in many biological processes. In particular, chemokines guide the migration of leukocytes during normal and inflammatory conditions. Recent studies reveal that the heterophilic interactions between chemokines significantly affect their biological activity, possibly representing a novel regulatory mechanism of the chemokine activities. The co-localization of platelet-derived chemokines in vivo allows them to interact. Here, we used nano-spray ionization mass spectrometry to screen eleven different CXC and CC platelet-derived chemokines for possible interactions with the two most abundant chemokines present in platelets, CXCL4 and CXCL7. Results indicate that many screened chemokines, although not all of them, form heterodimers with CXCL4 and/or CXCL7. In particular, a strong heterodimerization was observed between CXCL12 and CXCL4 or CXCL7. Compared to other chemokines, the main structural difference of CXCL12 is in the orientation and packing of the C-terminal alpha-helix in relation to the beta-sheet. The analysis of one possible structure of the CXCL4/CXCL12 heterodimer, CXC-type structure, using molecular dynamics (MD) trajectory reveals that CXCL4 may undergo a conformational transition to alter the alpha helix orientation. In this new orientation, the alpha-helix of CXCL4 aligns in parallel with the CXCL12 alpha-helix, an energetically more favorable conformation. Further, we determined that CXCL4 and CXCL12 physically interact to form heterodimers by co-immunoprecipitations from human platelets. Overall, our results highlight that many platelet-derived chemokines are capable of heterophilic interactions and strongly support future studies of the biological impact of these interactions.     

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases −8 and −9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNA-dependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and pro-survival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.     

Artificial selection on sexual aggression: Correlated traits and possible trade-offs

Forced copulation is an extreme form of sexual aggression that can affect the evolution of sex-specific anatomy, morphology, and behavior. To characterize mechanistic and evolutionary aspects of forced copulation, we artificially selected male fruit flies based on their ability to succeed in the naturally prevalent behavior of forced matings with newly eclosed (teneral) females. The low and high forced copulation lineages showed rapid divergence, with the high lineages ultimately showing twice the rates of forced copulation as the low lineages. While males from the high lineages spent more time aggressively pursuing and mounting teneral females, their behavior toward non-teneral and heterospecific females was similar to that of males from the low lineages. Males from the low and high lineages also showed similar levels of male-male aggression. This suggests little or no genetic correlations between sexual aggression and non-aggressive pursuit of females, and between male aggression toward females and males. Surprisingly however, males from the high lineages had twice as high mating success than males from the low lineages when allowed to compete for consensual mating with mature females. In further experiments, we found no evidence for trade-offs associated with high forced mating rates: males from the high lineages did not have lower longevity than males from the low lineages when housed with females, and four generations of relaxed selection did not lead to convergence in forced mating rates. Our data indicate complex interactions among forced copulation success and consensual mating behavior, which we hope to clarify in future genomic work.     

Comparative Proteomic Analysis of Supportive and Unsupportive Extracellular Matrix Substrates for Human Embryonic Stem Cell Maintenance

Human embryonic stem cells (hESCs) are pluripotent cells that have indefinite replicative potential and the ability to differentiate into derivatives of all three germ layers. hESCs are conventionally grown on mitotically inactivated mouse embryonic fibroblasts (MEFs) or feeder cells of human origin. In addition, feeder-free culture systems can be used to support hESCs, in which the adhesive substrate plays a key role in the regulation of stem cell self-renewal or differentiation. Extracellular matrix (ECM) components define the microenvironment of the niche for many types of stem cells, but their role in the maintenance of hESCs remains poorly understood. We used a proteomic approach to characterize in detail the composition and interaction networks of ECMs that support the growth of self-renewing hESCs. Whereas many ECM components were produced by supportive and unsupportive MEF and human placental stromal fibroblast feeder cells, some proteins were only expressed in supportive ECM, suggestive of a role in the maintenance of pluripotency. We show that identified candidate molecules can support attachment and self-renewal of hESCs alone (fibrillin-1) or in combination with fibronectin (perlecan, fibulin-2), in the absence of feeder cells. Together, these data highlight the importance of specific ECM interactions in the regulation of hESC phenotype and provide a resource for future studies of hESC self-renewal.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.