Search

Over 50 % of soil carbon (C) is stored in subsoil (below 30 cm). Inputs of labile C and nutrients can stimulate soil organic carbon (SOC) mineralization priming effect (PE) and subsequently affect subsoil C dynamics. However, little is known about the magnitude and mechanism of the PE occurring in subsoil, which complicates the prediction of subsoil C dynamics. Using a lab incubation experiment, the effects of glucose and nitrogen (N) addition on SOC mineralization were studied for three soil layers (0-10, 10-30, and 30-60 cm) from a subtropical forest. Five glucose (5.16 atom % C) levels were applied according to soil microbial biomass in each soil layer. Meanwhile, community-level physiological profiling was conducted to reflect microbial functional diversity and activity. We found positive PE for all soil layers. The PE magnitude in subsoil was about two times higher than that in topsoil with stronger increase in the microbial activity in mining components of SOC. N addition led to a reduction of 45 % in the PE magnitude in topsoil with relatively lower microbial activity in mining N-containing substrates (amino acids and amines) but caused an increase of 18 % in subsoil PE. Soil C and N availability were associated with microbial functional activity, the shifts of which then mediated the SOC mineralization in the presence of labile C and nutrient. These results suggested that mineralization of subsoil C was more sensitive to labile C and N addition. Any future changes in environmental conditions that affect the input and distribution of labile C and N in soil profiles could affect C dynamics in deep soil. [ABSTRACT FROM AUTHOR]

Conbercept is a recombinant fusion protein with high affinity for all vascular endothelial growth factor isoforms and placental growth factor. The repeated intravitreal injection of conbercept may cause intraocular pressure (IOP) fluctuations and long-term suppression of neurotrophic cytokines, which could lead to retinal nerve fiber layer (RNFL) damage. This retrospective fellow-eye controlled study included 98 eyes of 49 patients. The changes in IOP and RNFL thickness as well as the correlation between RNFL changes and associated factors were evaluated. The IOP value between the baseline and the last follow-up visit in the injection group and the IOP value of the last follow-up visit between the injection and non-injection groups were not significantly different (p = 0.452 and 0.476, respectively). The global average thickness of the RNFL (μm) in the injection group decreased from 108.9 to 106.1; however, the change was not statistically significant (p = 0.118). No significant difference in the average RNFL thickness was observed at the last follow-up visit between the injection and non-injection groups (p = 0.821). The type of disease was the only factor associated with RNFL thickness changes. In conclusion, repeated intravitreal injections with 0.05 mL conbercept revealed an excellent safety profile for RNFL thickness, although short-term IOP changes were observed. [ABSTRACT FROM AUTHOR]

TAp73 is a structural homologue of the pre-eminent tumour suppressor p53. However, unlike p53, TAp73 is rarely mutated, and instead is frequently overexpressed in human tumours. It remains unclear whether TAp73 affords an advantage to tumour cells and if so, what the underlying mechanism is. Here we show that TAp73 supports the proliferation of human and mouse tumour cells. TAp73 activates the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). By stimulating G6PD, TAp73 increases PPP flux and directs glucose to the production of NADPH and ribose, for the synthesis of macromolecules and detoxification of reactive oxygen species (ROS). The growth defect of TAp73-deficient cells can be rescued by either enforced G6PD expression or the presence of nucleosides plus an ROS scavenger. These findings establish a critical role for TAp73 in regulating metabolism, and connect TAp73 and the PPP to oncogenic cell growth. [ABSTRACT FROM AUTHOR]

Cellular senescence both protects multicellular organisms from cancer and contributes to their ageing. The pre-eminent tumour suppressor p53 has an important role in the induction and maintenance of senescence, but how it carries out this function remains poorly understood. In addition, although increasing evidence supports the idea that metabolic changes underlie many cell-fate decisions and p53-mediated tumour suppression, few connections between metabolic enzymes and senescence have been established. Here we describe a new mechanism by which p53 links these functions. We show that p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells. Both malic enzymes are important for NADPH production, lipogenesis and glutamine metabolism, but ME2 has a more profound effect. Through the inhibition of malic enzymes, p53 regulates cell metabolism and proliferation. Downregulation of ME1 and ME2 reciprocally activates p53 through distinct MDM2- and AMP-activated protein kinase-mediated mechanisms in a feed-forward manner, bolstering this pathway and enhancing p53 activation. Downregulation of ME1 and ME2 also modulates the outcome of p53 activation, leading to strong induction of senescence, but not apoptosis, whereas enforced expression of either malic enzyme suppresses senescence. Our findings define physiological functions of malic enzymes, demonstrate a positive-feedback mechanism that sustains p53 activation, and reveal a connection between metabolism and senescence mediated by p53. [ABSTRACT FROM AUTHOR]

Recent studies suggest that nuclear factor κB-inducing kinase (NIK) is suppressed through constitutive proteasome-mediated degradation regulated by TRAF2, TRAF3 and cIAP1 or cIAP2. Here we demonstrated that the degradation of NIK occurs upon assembly of a regulatory complex through TRAF3 recruitment of NIK and TRAF2 recruitment of cIAP1 and cIAP2. In contrast to TRAF2 and TRAF3, cIAP1 and cIAP2 seem to play redundant roles in the degradation of NIK, as inhibition of both cIAPs was required for noncanonical NF-κB activation and increased survival and proliferation of primary B lymphocytes. Furthermore, the lethality of TRAF3 deficiency in mice could be rescued by a single NIK gene, highlighting the importance of tightly regulated NIK. [ABSTRACT FROM AUTHOR]

An apoptotic signal triggered by cell surface death receptors is disseminated to intracellular compartments through protein–protein interactions mediated by conserved domains such as the death effector domain (DED). A unique family of single DED-containing proteins, including DEDD and DEDD2, is targeted to the nucleolus. However, the role of DEDD/DEDD2 in apoptosis remains less understood. Here we show that DEDD and DEDD2 are highly conserved in diverse species, and that they are potent inducers of apoptosis in various cell types. Deletion analysis indicates that both the N-terminal DED domain and the C-terminal region of DEDD2 can induce apoptosis. The cell death activity of this family appears to be related to their nuclear localization. DEDD and DEDD2 bind to two tandem DED-containing caspases, caspase -8 and -10, that are engaged by death receptors. Consistent with the nuclear localization of this family, caspase-8 translocates to the nucleus during CD95-induced apoptosis. DEDD and DEDD2 also readily associate with themselves and with each other. These results suggest that DEDD and DEDD2 may be important mediators for death receptors and that they may target caspases to the nucleus.Oncogene (2003) 22, 291–297. doi:10.1038/sj.onc.1206099 [ABSTRACT FROM AUTHOR]