Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

A new species of the genus Oxyporus Fabricius (Coleoptera: Staphylinidae: Oxyporinae) in Yunnan Province, China.

A new species of the genus Oxyporus Fabricius, 1775 is described based on specimens collected in Yunnan Province, China, namely Oxyporus (Oxyporus) tuantianius sp. nov. from Xinping County. The number of Oxyporus species worldwide is thus increased to 131. Color images of the habitus and aedeagus of the new species are included. A key to the Oxyporus species of Yunnan Province is provided.

Effects of extracellular potassium diffusion on electrically coupled neuron networks.

Potassium accumulation and diffusion during neuronal epileptiform activity have been observed experimentally, and potassium lateral diffusion has been suggested to play an important role in nonsynaptic neuron networks. We adopt a hippocampal CA1 pyramidal neuron network in a zero-calcium condition to better understand the influence of extracellular potassium dynamics on the stimulus-induced activity. The potassium concentration in the interstitial space for each neuron is regulated by potassium currents, Na(+)-K(+) pumps, glial buffering, and ion diffusion. In addition to potassium diffusion, nearby neurons are also coupled through gap junctions. Our results reveal that the latency of the first spike responding to stimulus monotonically decreases with increasing gap-junction conductance but is insensitive to potassium diffusive coupling. The duration of network oscillations shows a bell-like shape with increasing potassium diffusive coupling at weak gap-junction coupling. For modest electrical coupling, there is an optimal K(+) diffusion strength, at which the flow of potassium ions among the network neurons appropriately modulates interstitial potassium concentrations in a degree that provides the most favorable environment for the generation and continuance of the action potential waves in the network.

Enhanced multiple vibrational resonances by Na+ and K+ dynamics in a neuron model.

Some neuronal receptors perceive external input in the form of hybrid periodic signals. The signal detection may be based on the mechanism of vibrational resonance, in which a system's response to the low frequency signal can become optimal by an appropriate choice of the vibration amplitude of HFS. The vibrational resonance effect is investigated in a neuron model in which the intra- and extra-cellular potassium and sodium concentrations are allowed to evolve temporally, depending on ion currents, Na(+)-K(+) pumps, glial buffering, and ion diffusion. Our results reveal that, compared to the vibrational resonances in the model with constant ion concentrations, the significantly enhanced vibrational multi-resonances can be observed for the single neuron system where the potassium and sodium ion concentrations vary temporally. Thus, in contradiction to a popular view that ion concentrations dynamics play little role in signal detection, we indicate that the neuron's response to an external subthreshold signal can be largely improved by sodium and potassium dynamics.

Multistability in a neuron model with extracellular potassium dynamics.

Experiments show a primary role of extracellular potassium concentrations in neuronal hyperexcitability and in the generation of epileptiform bursting and depolarization blocks without synaptic mechanisms. We adopt a physiologically relevant hippocampal CA1 neuron model in a zero-calcium condition to better understand the function of extracellular potassium in neuronal seizurelike activities. The model neuron is surrounded by interstitial space in which potassium ions are able to accumulate. Potassium currents, Na{+}-K{+} pumps, glial buffering, and ion diffusion are regulatory mechanisms of extracellular potassium. We also consider a reduced model with a fixed potassium concentration. The bifurcation structure and spiking frequency of the two models are studied. We show that, besides hyperexcitability and bursting pattern modulation, the potassium dynamics can induce not only bistability but also tristability of different firing patterns. Our results reveal the emergence of the complex behavior of multistability due to the dynamical [K{+}]{o} modulation on neuronal activities.