Various studies, mostly in the past 5 years, have demonstrated that, in addition to their well-described function in regulating electrical excitability, voltage-dependent ion channels participate in ...intracellular signalling pathways. Channels can directly activate enzymes linked to cellular signalling pathways, serve as cell adhesion molecules or components of the cytoskeleton, and their activity can alter the expression of specific genes. Here, I review these findings and discuss the extent to which the molecular mechanisms of such signalling are understood.
Purpose To evaluate the effects of a novel ab interno trabeculectomy device on human trabecular meshwork (TM). Design Laboratory evaluation. Methods The TM from human cadaveric corneal rim tissue was ...incised using 3 instruments: (1) novel dual-blade device; (2) microvitreoretinal (MVR) blade; and (3) Trabectome. Tissue samples underwent histologic processing and comparative analyses. Subsequently, human eye perfusion studies were performed to evaluate intraocular pressure (IOP)-lowering effects of each device. Main outcome measures were degree of TM removal by histology and IOP in a perfusion model. Results The MVR blade exhibited minimal removal of TM and obvious injury to the adjacent sclera. The Trabectome removed a large portion of the central TM, but leaflets of residual tissue remained and thermal injury was noted in all samples. The dual-blade device achieved a more complete removal of TM without injury to surrounding tissues. All devices resulted in statistically significant lowering of IOP during perfusion model studies. MVR blade treatment across 170.0 ± 14.1 degrees of TM resulted in a decrease of IOP from 18.5 ± 1.9 mm Hg to 12.8 ± 2.2 mm Hg ( P < .01). Trabectome treatment across 117.5 ± 12.6 degrees resulted in a decrease of IOP from 18.8 ± 1.7 mm Hg to 11.3 ± 1.0 mm Hg ( P < .01). Dual-blade device treatment across 157.5 ± 26.3 degrees resulted in a decrease of IOP from 18.3 ± 3.0 mm Hg to 11.0 ± 2.2 mm Hg ( P < .01). Conclusions The novel dual-blade device demonstrated a more complete removal of TM without residual TM leaflets or damage to surrounding tissues and significantly reduced IOP in a human eye perfusion model.
Wound Modulation After Filtration Surgery Seibold, Leonard K., MD; Sherwood, Mark B., MD; Kahook, Malik Y., MD
Survey of ophthalmology,
11/2012, Letnik:
57, Številka:
6
Journal Article
Recenzirano
Abstract Filtration surgery is the standard invasive procedure for the management of intraocular pressure in advanced glaucoma. The key to a successful outcome is to modulate the normal wound healing ...cascade that leads to closure of the newly created aqueous outflow pathway. Antifibrotic agents such as mitomycin C and 5-fluorouracil have been increasingly used to modulate the wound healing process and increase surgical success. Although these agents have proven efficacy, they also increase the risk of complications. Efforts have centered on the identification of novel agents and techniques that can influence wound modulation without these complications. We detail new agents and methods under investigation to control wound healing after filtration surgery.
Mutations in the KCNT1 (Slack, KNa1.1) sodium-activated potassium channel produce severe epileptic encephalopathies. Expression in heterologous systems has shown that the disease-causing mutations ...give rise to channels that have increased current amplitude. It is not known, however, whether such gain of function occurs in human neurons, nor whether such increased KNa current is expected to suppress or increase the excitability of cortical neurons. Using genetically engineered human induced pluripotent stem cell (iPSC)-derived neurons, we have now found that sodium-dependent potassium currents are increased several-fold in neurons bearing a homozygous P924L mutation. In current-clamp recordings, the increased KNa current in neurons with the P924L mutation acts to shorten the duration of action potentials and to increase the amplitude of the afterhyperpolarization that follows each action potential. Strikingly, the number of action potentials that were evoked by depolarizing currents as well as maximal firing rates were increased in neurons expressing the mutant channel. In networks of spontaneously active neurons, the mean firing rate, the occurrence of rapid bursts of action potentials, and the intensity of firing during the burst were all increased in neurons with the P924L Slack mutation. The feasibility of an increased KNa current to increase firing rates independent of any compensatory changes was validated by numerical simulations. Our findings indicate that gain-of-function in Slack KNa channels causes hyperexcitability in both isolated neurons and in neural networks and occurs by a cell-autonomous mechanism that does not require network interactions.
The extraction and localization of an auditory stimulus of interest from among multiple other sounds, as in the 'cocktail-party' situation, requires neurons in auditory brainstem nuclei to encode the ...timing, frequency, and intensity of sounds with high fidelity, and to compare inputs coming from the two cochleae. Accurate localization of sounds requires certain neurons to fire at high rates with high temporal accuracy, a process that depends heavily on their intrinsic electrical properties. Studies have shown that the membrane properties of auditory brainstem neurons, particularly their potassium currents, are not fixed but are modulated in response to changes in the auditory environment. Here, we review work focusing on how such modulation of potassium channels is critical to shaping the firing pattern and accuracy of these neurons. We describe how insights into the role of specific channels have come from human gene mutations that impair localization of sounds in space. We also review how short-term and long-term modulation of these channels maximizes the extraction of auditory information, and how errors in the regulation of these channels contribute to deficits in decoding complex auditory information.
In situ tensile tests, accompanied by scanning electron microscopy coupled with electron backscatter diffraction (EBSD) analyses were performed on neutron-irradiated 304L steel specimens (5.9 dpa, ...irradiation in boiling water reactor at 288 °C). Selected regions of interest were analyzed following tensile deformation of the specimens to increasing levels of strain, allowing for tracking and investigating strain-induced misorientation evolution, lattice rotation, twinning, and phase instability. Deformation-induced changes in EBSD misorientation parameters, such as kernel average misorientation (KAM) and grain reference orientation deviation (GROD), were analyzed as a function of the strain level (ε). The mapping of GROD values revealed the formation of specific “hot spots” (areas with high local misorientation) in the early stages of tensile deformation (ε ∼0–0.02) with values increasing much more quickly for irradiated specimens than for nonirradiated specimens. In contrast, average KAM values showed very little change in the small strain range (ε < 0.02) and fast growth at larger strain values.
Soil erosion risk assessment in South-Kivu longs for the colonial epoch, while the province faces the problem of extreme degradation of land in the form of soil erosion. Thus, the study attempts to ...assess the soil erosion at the province level using the Revised Universal Soil Loss Equation (RUSLE) in conjunction with the Geographical Information System (GIS), and remote sensing data. The estimated total soil erosion was 2.084 million tons; with an annual average of 138.2 t ha
−1
yr
−1
. Moreover, the soil loss greater than 100 t ha
−1
yr
−1
accounts for 45.2% of the total erosive land. The soil erosion worsening nearly the entire territories range between 87 t ha
−1
yr
−1
in Shabunda to 248 t ha
−1
yr
−1
in Uvira. Under high aggressiveness of rainfall with mean of 1857.19 mm/y, the highest rate found in Perennial crop, Trees, and Cropland in contrast to Shrub and closed Forest was mainly due to the mean slope of 22% found in the former Land cover categories compared to 17% of Shrubland and closed forest. The adoption of terracing could reduce by 76% the current rate of cropland i.e., from (162.12 t ha
−1
yr
−1
to 38 t ha
−1
yr
−1
). Therefore it is strongly recommended.
During speech production, we make vocal tract movements with remarkable precision and speed. Our understanding of how the human brain achieves such proficient control is limited, in part due to the ...challenge of simultaneously acquiring high-resolution neural recordings and detailed vocal tract measurements. To overcome this challenge, we combined ultrasound and video monitoring of the supralaryngeal articulators (lips, jaw, and tongue) with electrocorticographic recordings from the cortical surface of 4 subjects (3 female, 1 male) to investigate how neural activity in the ventral sensory-motor cortex (vSMC) relates to measured articulator movement kinematics (position, speed, velocity, acceleration) during the production of English vowels. We found that high-gamma activity at many individual vSMC electrodes strongly encoded the kinematics of one or more articulators, but less so for vowel formants and vowel identity. Neural population decoding methods further revealed the structure of kinematic features that distinguish vowels. Encoding of articulator kinematics was sparsely distributed across time and primarily occurred during the time of vowel onset and offset. In contrast, encoding was low during the steady-state portion of the vowel, despite sustained neural activity at some electrodes. Significant representations were found for all kinematic parameters, but speed was the most robust. These findings enabled by direct vocal tract monitoring demonstrate novel insights into the representation of articulatory kinematic parameters encoded in the vSMC during speech production.
Speaking requires precise control and coordination of the vocal tract articulators (lips, jaw, and tongue). Despite the impressive proficiency with which humans move these articulators during speech production, our understanding of how the brain achieves such control is rudimentary, in part because the movements themselves are difficult to observe. By simultaneously measuring speech movements and the neural activity that gives rise to them, we demonstrate how neural activity in sensorimotor cortex produces complex, coordinated movements of the vocal tract.
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