Scorpion toxin peptide action at the ion channel subunit level

This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling

Lunar sample analysis

Results are presented from an extensive series of new high resolution scanning electron microscope studies of the very primative group of meteorites known as unequilibrated chondrites. These include quantitative analyses of micrometer sized phases and interpretation in terms of relevant phase equilibria. Several new meteorite minerals including high chromium metal, have been discovered

Type I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during cochlear development

<p>Abstract</p> <p>Background</p> <p>The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of spiral ganglion neuron (SGN) innervation to the inner hair cells (by type I SGNs) and the outer hair cells (by type II SGNs) is accompanied by a 25% loss of SGNs.</p> <p>Results</p> <p>We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the spiral ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF) added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis.</p> <p>Conclusion</p> <p>Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.</p

Fe-rich pentlandite in Allende bulk samples and separates: Mössbauer spectroscopy analysis.

Published versio

Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier.

The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses the gain of the 'cochlear amplifier' in each ear. Such efferent feedback is important for promoting discrimination of sounds in background noise, sound localization and protecting the cochleae from acoustic overstimulation. However, the sensory driver for the olivocochlear reflex is unknown. Here, we resolve this longstanding question using a mouse model null for the gene encoding the type III intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral ganglion neuron innervation of the outer hair cells, whereas innervation of the inner hair cells by type I spiral ganglion neurons was normal. Compared with Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent-mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice, demonstrating that outer hair cells and their type II afferents constitute the sensory drive for the olivocochlear efferent reflex

The Lowland Maya "Protoclassic"

The term "Protoclassic," employed regularly but inexplicitly in the literature of lowland Maya archaeology, has become increasingly nebulous and ambiguous in both meaning and usage. This paper reviews the history and use of the term and presents a formal redefinition of the Protoclassic as a ceramic stage based explicitly and exclusively on ceramic criteria. Some suggestions regarding future use of the term also are offered. The paper further addresses and resolves a number of persisting questions regarding Protoclassic orange wares, including problems concerning the actual existence of the "Aguacate ceramic group." and the relationships of Aguacate-group pottery to other emergent orange wares of the terminal Late Preclassic and initial Early Classic periods. The nature and significance of the "Holmul I Style," the "Floral Park Ceramic Sphere." and the relationships of the two to each other and the larger, redefined "protoclassic" ceramic stage also are examined. A spatial distribution for protoclassic ceramics considerably expanded over what has ever been reported previously is described, and chronometric data are presented to support a revised chronology for the protoclassic ceramic stage. Finally, ceramic data are offered that suggest a real subdivision of the protoclassic ceramic stage into an early, emergent facet originating entirely within Late Preclassic lowland traditions, and a later, fully "Classic" facet corresponding to the early Tzakol (Tzakol 1) ceramic horizon

Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection.

BACKGROUND: Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. METHODS: In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. RESULTS: We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). CONCLUSIONS: Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection

Observation of near-surface damage by phonon scattering

We have investigated the feasibility of phonon-reflection techniques as nondestructive means to probe surface and/or near-surface damage in otherwise highly perfect crystals. An UHV liquid-helium stage, suitable for phonon-reflection measurements, was installed on a beam line of a tandem van de Graaff accelerator which was used to implant MeV ions into the substrate in order to modify the surface region in situ. Here, we report our investigation on the effects of 1-MeV Ar+ implantation in Al2O3 single crystals by monitoring the reflection of terahertz (THz) phonons (50-Å wavelength) from the implanted region. The results are compared to other surface techniques. Using a 15-kV ion gun on the same beam line, we have also bombarded Al2O3 crystals coated with thin films of gold. The effects of a 7.5-keV Ar+ beam on this Au-Al2O3 system are also discussed in this paper

Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies

Central Nervous System (CNS) homeostasis and function rely on intercellular synchronization of metabolic pathways. Developmental and neurochemical imbalances arising from mutations are frequently associated with devastating and often intractable neurological dysfunction. In the absence of pharmacological treatment options, but with knowledge of the genetic cause underlying the pathophysiology, gene therapy holds promise for disease control. Consideration of leukodystrophies provide a case in point; we review cell type – specific expression pattern of the disease – causing genes and reflect on genetic and cellular treatment approaches including ex vivo hematopoietic stem cell gene therapies and in vivo approaches using adeno-associated virus (AAV) vectors. We link recent advances in vectorology to glial targeting directed towards gene therapies for specific leukodystrophies and related developmental or neurometabolic disorders affecting the CNS white matter and frame strategies for therapy development in future