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Biomass-derived carbon dots (C-dots) are considered a very important carbon material in metal ion detection of their small environmental impact, simple preparation process, and relatively low cost. A green approach for synthesizing biomass-derived C-dots from Chenpi using a hydrothermal method without further processing is proposed in the present study. The as-synthesized C-dots show excellent fluorescence properties, superior resistance to UV irradiation photobleaching, and high photostability in salt-containing solutions. The C-dots were used in the form of label-free fluorescent probes for sensitively detecting Hg2+ selectively. The outcome relationship behaved linearly and was established based on a given range between 10-300 nM concentration, with a detection limit of 7.0 nM. This green strategy obtains a high C-dot quantum yield of 10.8% and satisfactory results in detecting Hg2+ in actual water samples. [ABSTRACT FROM AUTHOR]

Tripartite motif 39 (Trim39) is a RING domain-containing E3 ubiquitin ligase able to inhibit the anaphase-promoting complex (APCIC) directly. Through analysis of Trim39 function in p53-positive and p53-negative cells, we have found, surprisingly, that p53-positive cells lacking Trim39 could not traverse the G1/S transition. This effect did not result from disinhibition of the APC/C. Moreover, although Trim39 loss inhibited etoposide-induced apoptosis in p53negative cells, apoptosis was enhanced by Trim39 knockdown in p53-positive cells. Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation. Depletion of Trim39 significantly increased p53 protein levels and cell growth retardation in multiple cell lines. We found that the relative importance of Trim39 and the well-characterized p53-directed E3 ligase, murine double minute 2 (MDM2), varied between cell types. In cells that were relatively insensitive to the MDM2 inhibitor, nutlin-3a, apoptosis could be markedly enhanced by siRNA directed against Trim39. As such, Trim39 may serve as a potential therapeutic target in tumors with WT p53 when MDM2 inhibition is insufficient to elevate p53 levels and apoptosis. [ABSTRACT FROM AUTHOR]

Apoptosis ensures tissue homeostasis in response to developmental cues or cellular damage. Recently reported genome-wide RNAi screens have suggested that several metabolic regulators can modulate caspase activation in Drosophila. Here, we establish a previously unrecognized link between metabolism and Drosophila apoptosis by showing that cellular NADPH levels modulate the initiator caspase Dronc through its phosphorylation at S130. Depletion of NADPH removed this inhibitory phosphorylation, resulting in the activation of Dronc and subsequent cell death. Conversely, upregulation of NADPH prevented Dronc-mediated apoptosis upon DIAP1 RNAi or cycloheximide treatment. Furthermore, this CaMKII-mediated phosphorylation of Dronc hindered Dronc activation, but not its catalytic activity. Blockade of NADPH production aggravated the death-inducing activity of Dronc in specific neurons, but not in the photoreceptor cells of the eyes of transgenic flies; similarly, non-phosphorylatable Dronc was more potent than wild type in triggering specific neuronal apoptosis. Our observations reveal a novel regulatory circuitry in Drosophila apoptosis, and, as NADPH levels are elevated in cancer cells, also provide a genetic model to understand aberrations in cancer cell apoptosis resulting from metabolic alterations. [ABSTRACT FROM AUTHOR]

Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B degradation is necessary, but not sufficient, for mitotic exit. Proteins phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated. We report here that protein phosphatase-1 (PP1) is the main catalyst of mitotic phosphoprotein dephosphorylation. Suppression of PP1 during early mitosis is maintained through dual inhibition by Cdc2 phosphorylation and the binding of inhibitor-1. Protein kinase A (PKA) phosphorylates inhibitor-1, mediating binding to PP1. As Cdc2 levels drop after cyclin B degradation, auto-dephosphorylation of PP1 at its Cdc2 phosphorylation site (Thr 320) allows partial PP1 activation. This promotes PP1-regulated dephosphorylation at the activating site of inhibitor-1 (Thr 35) followed by dissociation of the inhibitor-1–PP1 complex and then full PP1 activation to promote mitotic exit. Thus, Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated dephosphorylation. [ABSTRACT FROM AUTHOR]

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF). which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase. [ABSTRACT FROM AUTHOR]

A carboxymethyl chitosan (CMC)-assisted method is developed for the preparation of a palladium (Pd) nanoparticles (NPs)/carbon nanotubes (CNTs) nanohybrid. The addition of a small amount of CMC to the reaction solution leads to the production of well-crystallised metallic Pd NPs with small diameter and uniformly dispersed on CNTs. The obtained Pd NPs supported on CNTs show enhanced catalytic activity and stability for the electrochemical oxidation of methanol in alkaline media. The as-developed Pd NPs/CNTs nanohybrid is a highly promising catalyst for use in fuel cell technology. [ABSTRACT FROM AUTHOR]

Notch signaling plays an important role in arterial-venous specification during embryogenesis. However, the role of Notch signaling in lymphatic development is poorly understood. Here, we show that activated Notch and its downstream effectors, Hey1 and Hey2, repress the expression of the master control gene of lymphatic development Prox1, and induce arterial phenotypes in human lymphatic endothelial cells (LECs). We then translated our findings to define the molecular basis for the disturbed lymphatic development of nuchal edema (NE) of aneuploid human fetuses. We found that Hey1 was upregulated in LECs of developing jugular lymph sacs (JLS) of Down syndrome fetuses, whereas Prox1, LYVE-1 and podoplanin were down-regulated. Moreover, the arterial markers ephrinB2 and neuropilin-1 were upregulated and the venous marker EphB4 was transiently expressed. These data indicate that JLS endothelial ceils of NE fetuses arrested lymphatic differentiation program, regained venous phenotype and acquired arterial endothelial cell identity. We propose that dysregulated Notch signaling induces pathological arterialization of developing lymphatic vessels in human Down syndrome fetuses with NE. [ABSTRACT FROM AUTHOR]

Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. It was previously reported that modulator of apoptosis protein 1 (MOAP-1), an enhancer of Bax activation induced by DNA damage, is stabilized by Trim39, a protein of unknown function. In this paper, we show that MOAP-1 is a novel substrate of the anaphase-promoting complex (APC/CCdh1) ubiquitin ligase. The influence of Trim39 on MOAP-1 levels stems from the ability of Trim39 (a RING domain E3 ligase) to directly inhibit APC/CCdh1-mediated protein ubiquitylation. Accordingly, small interfering ribonucleic acid-mediated knockdown of Cdh1 stabilized MOAP-1, thereby enhancing etoposide-induced Bax activation and apoptosis. These data identify Trim39 as a novel APC/C regulator and provide an unexpected link between the APC/C and apoptotic regulation via MOAP-1. [ABSTRACT FROM AUTHOR]