Indirect evidence suggests that excitatory amino acids (EAA) are involved in synaptic transmission of visceral afferents at their synapses within the nucleus tractus solitarius (NTS). Little is known about the identity of the postsynaptic receptors or response mechanisms. Here we report results from a longitudinal brain slice of the rat medulla. Intracellular recordings were made from neurons in delimited portions of the dorsal medial NTS (mNTS) known to receive baroreceptor inputs. Stimulation of the solitary tract 1-3 mm from the mNTS recording site evoked short (2 ms) latency excitatory postsynaptic potentials (EPSPs), which had durations of 40-50 ms. Addition of the non-N-methyl-D-aspartate (non-NMDA) selective antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) to the slice surface near the recording electrode resulted in a rapid (within 30-45 s) suppression of the EPSP. Complete EPSP blockade was only slowly reversed by drug-free saline. Concentration-response relations (n = 14) showed 50% depression of EPSPs by surface concentrations of 1-10 microM CNQX. EPSP amplitude was resistant to the selective NMDA antagonist 2-amino-5-phosphonovalerate (AP 5) and, on average, was reduced less than 20% at 100 microM AP 5, an effect that was not statistically significant (n = 10; P greater than 0.05). In conclusion, this study offers the first direct evidence that EAAs mediate the primary events of afferent synaptic transmission in NTS. The experiments suggest that excitatory sensory afferent synaptic transmission to mNTS neurons is mediated by an EAA transmitter acting at non-NMDA receptors, but NMDA receptors may have a modulatory role.

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Based on these results, it is suggested that the rich geological and ecological diversity caused by the recent large-scale uplifts of the Qinghai-Tibetan Plateau since the late Tertiary, coupled with the oscillating climate of the Quaternary stage, might have promoted rapid speciation in small and isolated populations, as well as allowing the fixation of unique or rare morphological characters in Rheum. Such a rapid radiation, combined with introgressive hybridization and reticulate evolution, may have caused the transfer of cpDNA haplotypes between morphologically dissimilar species, and might account for the inconsistency between morphological classification and molecular phylogeny reported here.

The aesthetic surgeon may occasionally be consulted by a patient who wishes to discuss what can be done for the scars of self-inflicted wounds on the forearms. These scars are popularly referred to as "hesitation marks" or "suicide gestures." Unlike patients suffering from factitial ulcers or Münchhausen syndrome, these patients will admit to the physician that the scars are the result of self-inflicted wounds. These scars often consist of multiple, parallel, white lines extending up and down the forearms (usually volar surface), with more on the nondominant side. Although the pattern of these scars is apparently what drives these patients to the aesthetic surgeon for relief (because even lay people identify these scars as self-inflicted suicide marks), the authors propose a new and deeper motivation for surgery. Recent experiences with three of these patients resulted in an epiphany that prompted this report. Once the symbolic meaning of these scars was broached, a torrent of thoughts and theories followed. This article will recount these three cases and present a central thesis for this type of self-inflicted injury. A proposal for the proper surgical treatment of this condition will be offered. Uniquely, two of the patients will relate their own stories and propose guidelines and warnings for the aesthetic surgeon.

Purpose Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC). Methods KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot. Results The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated β-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression. Conclusion Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.

1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to solitary tract (ST) activation were studied in a horizontal brain slice preparation of the rat medulla. Slices included sections of ST sufficiently long that the ST could be electrically activated several millimeters from the recording site of cell bodies in mNTS. 2. Three types of synaptic events were evoked in response to ST stimulation: simple excitatory postsynaptic potentials (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/- 0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP amplitude increased linearly with increasing hyperpolarization, with an extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With 1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5. With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally comparable average EPSPs were evoked during constant and burst patterns of ST stimulation. The amplitude of the initial EPSP in each burst was very well maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited action potentials and suppressed spontaneous spiking, but higher frequencies led to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic stimulation-suppression cycle clearly entrained action potential activity to the ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action potentials with each pulse to higher frequencies (50 Hz) without failures, and entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as 50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST stimulation frequency-response relation of these IPSPs was similar to that for the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear to be activated polysynaptically via a glutamatergic-GABAergic sequence in response to ST activation. 9. The results suggest that sensory afferent synapses in mNTS have limited transmission of high-frequency inputs. Both synaptic transmission and the characteristics of the postsynaptic neuron importantly contribute to the action potential transmission from afferent to NTS neuron and beyond. This overall frequency response limitation may contribute to the accommodat...

FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active β-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3β, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

I . Pressure threshold (Pth) and suprathreshold pressure sensitivity (Sth) are important measures of the pressure-discharge characteristics of arterial baroreceptors. An in vitro preparation of the rat aortic arch-aortic nerve has been used to assess the influence of extracellular ion concentration, distensibility, smooth muscle activation and rapid resetting on single fibre baroreceptor discharge.2. Changes in extracellular cations alter Pth and Sth in a reciprocal manner, suggesting that these two properties share common excitatory mechanisms probably at the level of membrane ion conductance channels.3. During normal development and ageing in normotensive rats, Pth and blood pressure are fairly constant even during periods of greatly changing aortic distensibility. Sth increases progressively to maturity and then decreases somewhat with advanced age.4. During hypertension, changes in distensibility in spontaneously hypertensive rats do not account for changes in Pth and Sth.5. The capacity of arterial baroreceptors t o rapidly reset during acute changes in the conditioning mean arterial pressure is not altered by chronic resetting, decreases in distensibility or by differences in the initial Pth or Sth of individual baroreceptors.6. Within the maximal physiological or pathophysiological range, the prevailing or conditioning mean arterial pressure appears to be the most potent modulator of arterial baroreceptor discharge.