Alpha9 nicotinic acetylcholine receptors and the treatment of pain

Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits.Fil: McIntosh, J. Michael. University of Utah; Estados UnidosFil: Absalom, Nathan. The University of Sydney; AustraliaFil: Chebib, Mary. The University of Sydney; AustraliaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Vincler, Michelle. Wake Forest University Health Sciences; Estados Unido

Dynamical Complexity, Intermittent Turbulence, Coarse-Grained Dissipation, Criticality and Multifractal Processes

The ideas of dynamical complexity induced intermittent turbulence by sporadic localized interactions of coherent structures are discussed. In particular, we address the phenomenon of magnetic reconfiguration due to coarse-grained dissipation as well as the interwoven connection between criticality and multifractal processes. Specific examples are provided.Comment: 6 pages, 2 figures, submitted to AIP Conference Proceedings for the 6th Annual International Astrophysics Conference, Honolulu, March 16-22, 200

School-leavers' Transition to Tertiary Study: a Literature Review.

The theoretical and empirical literature relating to factors and problems in the transition of students from secondary to tertiary level education is reviewed here. Studies on persistence and attrition, and on the analysis and prediction of academic performance of students, generally and in particular discipline areas, are included.Transition to university; student performance.

The multifaceted role of astrocytes in regulating myelination

Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS

Acute kidney injury in the elderly: predisposition to chronic kidney disease and vice versa.

There have been considerable advances in the past few years in our understanding of how chronic kidney disease (CKD) predisposes to acute kidney injury (AKI) and vice versa. This review shows, however, that few studies have focused on the elderly or conducted stratified analysis by age. It does appear that elderly patients with estimated glomerular filtration rate (eGFR) 45-59 ml/min/1.73 m(2) are at higher risk for AKI compared with their counterparts with eGFR >60 ml/min/1.73 m(2). This is a similar relationship to that seen in younger patients, although effect size appears smaller. As the incidence of AKI has been increasing over the past several years, the proportion of elderly patients surviving after AKI has also been increasing. Since AKI heightens the risk for the development and acceleration of CKD, this implies significant public health concerns with regard to the absolute number of elderly persons developing incident CKD

Enhanced Magnetization from Proton Irradiated Bulk van der Waals Magnet CrSiTe3

Van der Waals (vdWs) crystals have attracted a great deal of scientific attention due to their interesting physical properties and widespread practical applications. Among all, CrSiTe3 (CST) is a ferromagnetic semiconductor with the Curie temperature (TC) of ~32 K. In this letter, we study the magnetic properties of bulk CST single-crystal upon proton irradiation with the fluence of 1x1018 protons/cm2. Most significantly, we observed an enhancement (23%) in the saturation magnetization from 3.9 {\mu}B to 4.8 {\mu}B and is accompanied by an increase in the coercive field (465-542 Oe) upon proton irradiation. Temperature-dependent X-band electron paramagnetic resonance measurements show no additional magnetically active defects/vacancies that are generated upon proton irradiation. The findings from X-ray photoelectron spectroscopy and Raman measurements lead us to believe that modification in the spin-lattice coupling and introduction of disorder could cause enhancement in saturation magnetization. This work demonstrates that proton irradiation is a feasible method in modifying the magnetic properties of vdWs crystals, which represents a significant step forward in designing future spintronic and magneto-electronic applications