Stabilizing ER Ca2+ Channel Function as an Early Preventative Strategy for Alzheimer’s Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca²⁺ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca²⁺ signaling, predominantly through the ER-localized inositol triphosphate (IP₃) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca²⁺ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca²⁺ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca²⁺ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca²⁺ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients.     

A molecular dynamics study of the stoichiometric complex formed by poly (alpha, L-glutamate) and octyltrimethylammonium ions in chloroform solution.

We present a molecular dynamics simulation at 300 K in explicit solvent environment of chloroform of the stoichiometric complex formed by poly(alpha,L-glutamate) and octyltrimethylammonium ions. We observed that the alpha-helix conformation of the polypeptide chain remains stable during a 2-ns run. The surfactant ions predominantly adopted an extended conformation that is stabilized by favorable interactions with the organic solvent. Analysis of the organization of the surfactant with respect to the polypeptide chain indicated that each octyltrimethylammonium cation was preferentially bound to more than one carboxylate group. It was found that the most populated arrangement was that with the surfactant cations interacting with two carboxylate groups simultaneously.     

Four New Diterpenoid Alkaloids from The Roots of Aconitum coreanum

Four new hetisine‐type C₂₀‐diterpenoid alkaloids, named as coreanines A–D ( 1 – 4 ), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids ( 5 – 17 ). Their structures were elucidated by extensive spectroscopic methods including IR, HR‐ESI‐MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity.     

Nonthermal Plasma‐Induced Degradation of Morin and Enhancement of Biological Activities

In the present study, non‐thermal dielectric barrier discharge (DBD) plasma of induced structural changes of morin resulted in the isolation of one previously undescribed benzofuranone derivative, along with two known compounds. The chemical structures of these degradation products were elucidated by UV, NMR and FAB‐MS spectroscopic analyses. The isolated three compounds showed potent antioxidative activities in two different tests, with IC₅₀ values in the range of 12.9–41.8 μm in the 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS⁺) radical scavenging activity, 19.0–71.9 μm for hydroxyl radical scavenging activity test. Furthermore, the new methoxylated benzofuranone exhibited enhancement of inhibitory effects against pancreatic lipase with an IC₅₀ value of 90.7±1.6 μm , when compared to the parent morin. These results suggested that the degradation products isolated from plasma exposed morin might be beneficial for prevention of obesity and related diseases.     

Effect of microwave treatment on the shear bond strength of different types of commercial teeth to acrylic resin

doi:10.1111/j.1741‐2358.2009.00333.x
Effect of microwave treatment on the shear bond strength of different types of commercial teeth to acrylic resin Objective: The purpose of this study was to verify the effect of microwave treatment on the shear bond strength of commercial types of teeth to acrylic resin, when the glossy ridge laps were unmodified (groups 1 and 5), bur abraded (groups 2 and 6), bur grooved (groups 3 and 7) or etched by monomer (groups 4 and 8). Background: Controversial findings have shown that mechanical or chemical changes in ridge‐lap surface of the tooth increase or decrease the bond strength between tooth and acrylic resin, and the microwave disinfection may cause different changes on this bond strength. Materials and methods: Eighty specimens (n = 10) were made with the acrylic resin bonded to tooth glossy ridge lap, polymerised in water at 74°C for 9 h, and deflasked after flask cooling. Specimens of the groups 5, 6, 7 and 8 were individually immersed in 150 ml of water and submitted to microwave treatment in an oven at 650 W for 3 min. Control specimens (groups 1, 2, 3 and 4) were not microwave treated. Shear bond strength test was performed in an Instron machine with a cross‐speed of 1 mm/min. Collected data were submitted to anova and Tukey’s test (α = 0.05). Results: Microwave treatment decreased the shear bond strength values of the tooth/resin bond. In the microwaved and non‐microwaved procedures, mechanical retention improved the shear bond strength when compared with the control and monomer treatments. Conclusion: Shear bond strength of the tooth/resin bond was influenced by the microwave treatment and different commercial teeth association, and was lower for the Biotone tooth.     

Heritability of Eating Behavior Assessed Using the DEBQ (Dutch Eating Behavior Questionnaire) and Weight‐related Traits: The Healthy Twin Study

The heritability of eating behavior and body weight–related traits in Asian populations has not been reported. The purpose of this study was to estimate the heritability of eating behavior and the body weight–related traits of current weight and self‐reported past weight among twins and their families. Study subjects were 2,144 Korean, adult, same‐sex twins and their families at the ages between 20 and 65 years (443 monozygotic (MZ) and 124 dizygotic (DZ) twin pairs, and 1,010 individuals of their family). The Dutch Eating Behavior Questionnaire (DEBQ) was used to assess three eating behavior subscales measuring restraint, emotional eating, and external eating. A variance component approach was used to estimate heritability. After consideration of shared environmental effects and adjustment for age and sex effects, the heritability estimates ± s.e. among twins and their family members were 0.31 ± 0.036 for restraint, 0.25 ± 0.098 for emotional eating, 0.25 ± 0.060 for external eating, 0.77 ± 0.032 for measured current body weight, and 0.70 ± 0.051 for self‐reported weight at 20 years old. The three DEBQ subscales were associated with all weight related traits after adjustment for age and sex. These results suggest eating behaviors and weight‐related traits have a genetic influence, and eating behaviors are associated with obesity indexes. Our findings from Korean twin family were similar to those reported in Western populations.     

Radio frequency radiation causes no nonthermal damage in enzymes and living cells

The ability of radio frequency radiation (RFR) to exert irreversible nonthermal (i.e., not caused by accompanying heat) effects on biologics has been widely debated due to a relative paucity of comprehensive critical details in published reports dealing with this issue. In this study, we used rigorous control over experimental conditions to determine whether continuous RFR nonthermally affects commercially important enzymes and live bacterial and human cells using three most commonly used frequencies in current RF identification technology, namely 2.45 GHz, 915 MHz, and 13.56 MHz. Diverse biological samples were exposed to RFR under deliberately harsh conditions to increase the likelihood of observing such effects should they exist. Enzymatic activities of horseradish peroxidase and β‐galactosidase in aqueous solution exhibited no statistically discernable consequences of even very intense RFR. Likewise, with putative thermal effects excluded, the viabilities of bacteria (both gram‐positive and gram‐negative) and of human cells were not detectably compromised by such an RFR exposure. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Three sisters in the same dress: cryptic speciation in African odonates

The discovery of cryptic species (i.e. two or more distinct but morphologically undistinguishable species) has grown exponentially in the last two decades, due mainly to the increasing availability of DNA sequences. This suggests that hidden in the known species, many of which have been described based solely on morphological information, there might be a high number of species waiting to be discovered. In this issue Damm et al. (2010) use a combination of genetic, morphological and ecological evidence to identify the first cryptic species complex found within dragonflies (insect order Odonata). Their findings add more evidence for the importance of combining information from different disciplines to new species’ discovery ( DeSalle et al. 2005 ).