Summary:Purpose: The anterior nucleus of the thalamus (ANT) modulates temporal lobe and hypothalamic activities, and relays information to the cingulate gyrus and entorhinal cortex. Deep brain stimulation (DBS) of the ANT has been reported to decrease seizure activity in a limited number of human subjects. However, long-term effect of chronic ANT stimulation on such patients remains unknown. We report long-term follow-up results in four patients receiving ANT stimulation for intractable epilepsy.Methods: Four patients underwent stereotactic implantation of quadripolar stimulating electrodes in the bilateral ANT, guided by single-unit microelectrode recording. Electrode location was confirmed by postoperative magnetic resonance imaging (MRI). The stimulator was activated 2-4 weeks following electrode insertion; initial stimulation parameters were 4-5 V, 90-110 Hz, and 60-90 µs. Seizure frequency was monitored and compared with preimplantation baseline frequency. Intelligence quotient (IQ) test and auditory P300 response were performed before and after implantation of electrodes.Results: Four patients (one man with generalized seizures, and three women with partial seizures and secondary generalization) aged 18-45 years old were studied with mean followup period of 43.8 months. The four patients demonstrated a sustained effect of 49% (range, 35-76%) seizure reduction to ANT stimulation. Simple insertion of DBS electrodes (Sham period, no stimulation) produced a mean reduction in seizures of 67% (range, 44-94%). One patient was seizure-free for 15 months with anticonvulsant medications. One patient had a small frontal hemorrhage and a second patient had extension erosion over scalp; no resultant major or permanent neurological deficit was observed. Preoperative IQ index and auditory P300 were not significantly different with those after electrodes implantation.Conclusions: Implantation of electrodes in the ANT and subsequent stimulation is associated with a significant reduction in seizure frequency. However, our study could not differentiate whether the implantation itself, the subsequent stimulation or postimplantation drug manipulation had the greatest impact. These experimental results prompt further controlled study in a large patient population.
Fas apoptotic signaling regulates diverse physiological processes. Acute activation of Fas signaling triggers massive apoptosis in liver. Upon Fas receptor stimulation, the BH3-only protein Bid is cleaved into the active form, tBid. Subsequent tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM), is a critical step for commitment to apoptosis via the effector proteins Bax or Bak. MOAP-1 is a Bax-binding protein enriched at the OMM. Here, we show that MOAP-1-deficient mice are resistant to Fas-induced hepatocellular apoptosis and lethality. In the absence of MOAP-1, mitochondrial accumulation of tBid is markedly impaired. MOAP-1 binds to MTCH2, and this interaction appears necessary for MTCH2 to engage tBid. These findings reveal a role for MOAP-1 in Fas signaling in the liver by promoting MTCH2-mediated tBid recruitment to mitochondria.
Background: MOAP-1 is a pro-apoptotic protein.Results: MOAP-1 expression is reduced in cancers and high expression correlated with increased patient survival. MOAP-1 can associate with tubulin and modulate tubulin stability. Furthermore, loss of the BH3 domain of MOAP-1 resulted in lack of tumor suppressor function.Conclusion: MOAP-1 is a highly regulated tumor suppressor protein.Significance: The loss of MOAP-1 may significantly contribute to tumorigenesis.
Metamaterials composed of metallic antennae arrays are used as they possess extraordinary optical transmission (EOT) in the terahertz (THz) region, whereby a giant forward light propagation can be created using constructive interference of tunneling surface plasmonic waves. However, numerous applications of THz meta-devices demand an active manipulation of the THz beam in free space. Although some studies have been carried out to control the EOT for the THz region, few of these are based upon electrical modulation of the EOT phenomenon, and novel strategies are required for actively and dynamically reconfigurable EOT meta-devices. In this work, we experimentally present that the EOT resonance can be coupled to optically reconfigurable chalcogenide metamaterials which offers a reversible all-optical control of the THz light. A modulation efficiency of 88% in transmission at 0.85 THz is experimentally observed using the EOT metamaterials, which is composed of a gold (Au) circular aperture array sitting on a non-volatile chalcogenide phase change material (Ge 2 Sb 2 Te 5 ) film. This comes up with a robust and ultrafast reconfigurable EOT over 20 times of switching, excited by a nanosecond pulsed laser. The measured data have a good agreement with finite-element-method numerical simulation. This work promises THz modulators with significant on/off ratios and fast speeds.
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