Regulation of Na(+) channel inactivation by the DIII and DIV voltage-sensing domains.

Functional eukaryotic voltage-gated Na(+) (NaV) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical NaV channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair NaV channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery

Portable Infrared Pupillometer in Patients With Subarachnoid Hemorrhage: Prognostic Value and Circadian Rhythm of the Neurological Pupil Index (NPi)

Background: Portable automated infrared pupillometry is becoming increasingly popular. To generate an objective reference base, the Neurological Pupil index (NPi) which combines different values of the pupillary light reflex is being introduced into clinical practice. In this explorative study, we examined different aspects of the NPi in relation to clinical severity and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Materials and Methods: Patients with serial assessment of the NPi (NeurOptics pupillometer NPi-200, Irvine, CA) starting no later than day 2 after aSAH onset were included in the study. Relative numbers of pathologic NPi’s, absolute NPi values, and their variances were compared according to aSAH clinical severity grade, functional outcome, and case fatality. The correlation between NPi and intracranial pressure, and NPi periodicity, were also examined. Results: In total, 18 patients with 4456 NPi values were eligible for inclusion in the analysis. The general trend of the NPi over time reflected the course of the neurological illness. Mean NPi tended to be lower in patients with clinically severe compared with nonsevere aSAH (3.75±0.40 vs. 4.56±0.06; P=0.171), and in patients with unfavorable compared with favorable outcomes (3.64±0.48 vs. 4.50±0.08; P=0.198). The mean variance of the NPi was higher in patients with severe compared with nonsevere aSAH (0.49±0.17 vs. 0.06±0.02; P=0.025). Pathologic NPi values were recorded more frequently in patients with severe compared with nonsevere aSAH (16.3%±8.8% vs. 0.0%±0.0%; P=0.002), and in those with unfavorable compared with favorable outcomes (19.2%±10.6% vs. 0.7%±0.6%; P=0.017). NPi was inversely correlated with intracranial pressure (Spearman r=−0.551, P<0.001). We observed a circadian pattern of NPi’s which was seemingly disrupted in patients with fatal outcome. Conclusions: On the basis of this preliminary study, the assessment of NPi by pupillometry is feasible and might complement multimodal neuromonitoring in patients with aSAH

Localization by disorder in the infrared conductivity of (Y,Pr)Ba2Cu3O7 films

The ab-plane reflectivity of (Y{1-x}Prx)Ba2Cu3O7 thin films was measured in the 30-30000 cm-1 range for samples with x = 0 (Tc = 90 K), x = 0.4 (Tc = 35 K) and x = 0.5 (Tc = 19 K) as a function of temperature in the normal state. The effective charge density obtained from the integrated spectral weight decreases with increasing x. The variation is consistent with the higher dc resistivity for x = 0.4, but is one order of magnitude smaller than what would be expected for x = 0.5. In the latter sample, the conductivity is dominated at all temperatures by a large localization peak. Its magnitude increases as the temperature decreases. We relate this peak to the dc resistivity enhancement. A simple localization-by-disorder model accounts for the optical conductivity of the x = 0.5 sample.Comment: 7 pages with (4) figures include

Wildlife survey along the Rawog River Conservation Area, Segaliud Lokan Forest Reserve

The Rawog river that stretched along the Rawog Conservation Area is one of the two rivers within the Segaliud Lokan Forest Reserve. Nonetheless, there is still scarce studies that document the wildlife that inhabit along this river. As such, limited information is available to describe the qualities of the Rawog river as part of the protected area. Therefore, this study was conducted during the Rawog Scientific Expedition with the aim to document and update the wildlife that includes birds, terrestrial mammals and crocodile that can be found along that river. Opportunistic observation survey was conducted for both morning and night sessions during the 4 days of expedition. A total of 61 individuals from 31 species and 24 families of wildlife were recorded. Interestingly, there were Endangered species of bird namely the Storm's Stork (Ciconia stormi) and one species with Vulnerable status that is Greater Green Leafbird (Chloropsis sonnerati) sighted during the survey. Meanwhile, for terrestrial mammals, there one Endangered species namely the Flat-headed cat (Prionailurus planiceps) and one Near-Threatened species of amphibian of which, is the Greater Swamp Frog (Limnonectes ingeri) were also able to be recorded even though there were no crocodile spotted during the survey. The result from this preliminary survey showed that the Rawog river play an important role in supporting diverse species of wildlife and worth to be retained as the fully protected area inside the Segaliud Lokan Forest Reserve

Electrical transport and magnetic properties of nanostructured La0.67Ca0.33MnO3

Nanostructured La0.67Ca0.33MnO3 (NS-LCMO) was formed by pulsed-laser deposition on the surface of porous Al2O3. The resistance peak temperature (Tp) of the NS-LCMO increases with increasing average thickness of the films, while their Curie temperatures (Tc) remain unchanged. The coercive field of the samples increases with decreasing film thickness and its temperature dependence can be well described by Hc(T) = Hc(0)[1-(T/TB)1/2]. A large magnetoresistance and strong memory effect were observed for the NS-LCMO. The results are discussed in terms of the size effect, Coulomb blockade and magnetic tunneling effect. This work also demonstrates a new way to get nanostructured manganites

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease

The Composite Effect of Transgenic Plant Volatiles for Acquired Immunity to Herbivory Caused by Inter-Plant Communications

A blend of volatile organic compounds (VOCs) emitted from plants induced by herbivory enables the priming of defensive responses in neighboring plants. These effects may provide insights useful for pest control achieved with transgenic-plant-emitted volatiles. We therefore investigated, under both laboratory and greenhouse conditions, the priming of defense responses in plants (lima bean and corn) by exposing them to transgenic-plant-volatiles (VOCos) including (E)-β-ocimene, emitted from transgenic tobacco plants (NtOS2) that were constitutively overexpressing (E)-β-ocimene synthase. When lima bean plants that had previously been placed downwind of NtOS2 in an open-flow tunnel were infested by spider mites, they were more defensive to spider mites and more attractive to predatory mites, in comparison to the infested plants that had been placed downwind of wild-type tobacco plants. This was similarly observed when the NtOS2-downwind maize plants were infested with Mythimna separata larvae, resulting in reduced larval growth and greater attraction of parasitic wasps (Cotesia kariyai). In a greenhouse experiment, we also found that lima bean plants (VOCos-receiver plants) placed near NtOS2 were more attractive when damaged by spider mites, in comparison to the infested plants that had been placed near the wild-type plants. More intriguingly, VOCs emitted from infested VOCos-receiver plants affected their conspecific neighboring plants to prime indirect defenses in response to herbivory. Altogether, these data suggest that transgenic-plant-emitted volatiles can enhance the ability to prime indirect defenses via both plant-plant and plant-plant-plant communications

Mutations underlying 3-Hydroxy-3-Methylglutaryl CoA Lyase deficiency in the Saudi population

BACKGROUND: 3-Hydroxy-3-Methylglutaric aciduria (3HMG, McKusick: 246450) is an autosomal recessive branched chain organic aciduria caused by deficiency of the enzyme 3-Hydroxy-3-Methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). HL is encoded by HMGCL gene and many mutations have been reported. 3HMG is commonly observed in Saudi Arabia. METHODS: We utilized Whole Genome Amplification (WGA), PCR and direct sequencing to identify mutations underlying 3HMG in the Saudi population. Two patients from two unrelated families and thirty-four 3HMG positive dried blood spots (DBS) were included. RESULTS: We detected the common missense mutation R41Q in 89% of the tested alleles (64 alleles). 2 alleles carried the frame shift mutation F305fs (-2) and the last two alleles had a novel splice site donor IVS6+1G>A mutation which was confirmed by its absence in more than 100 chromosomes from the normal population. All mutations were present in a homozygous state, reflecting extensive consanguinity. The high frequency of R41Q is consistent with a founder effect. Together the three mutations described account for >94% of the pathogenic mutations underlying 3HMG in Saudi Arabia. CONCLUSION: Our study provides the most extensive genotype analysis on 3HMG patients from Saudi Arabia. Our findings have direct implications on rapid molecular diagnosis, prenatal and pre-implantation diagnosis and population based prevention programs directed towards 3HMG