Oxygen: a master regulator of pancreatic development?

Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector of many developmental events. The oxygen‐sensing machinery and the very fabric of cell identity and function have been shown to be deeply intertwined. Here we take a first look at how oxygen might lie at the crossroads of at least two of the major molecular pathways that shape pancreatic development. Based on recent evidence and a thorough review of the literature, we present a theoretical model whereby evolving oxygen tensions might choreograph to a large extent the sequence of molecular events resulting in the development of the organ. In particular, we propose that lower oxygenation prior to the expansion of the vasculature may favour HIF (hypoxia inducible factor)‐mediated activation of Notch and repression of Wnt/β‐catenin signalling, limiting endocrine cell differentiation. With the development of vasculature and improved oxygen delivery to the developing organ, HIF‐mediated support for Notch signalling may decline while the β‐catenin‐directed Wnt signalling is favoured, which would support endocrine cell differentiation and perhaps exocrine cell proliferation/differentiation.     

REtools: A laboratory program for restriction enzyme work: enzyme selection and reaction condition assistance

Background  

Restriction enzymes are one of the everyday tools used in molecular biology. The continuously expanding panel of known restriction enzymes (several thousands) renders their optimal use virtually impossible without computerized assistance. Several manufacturers propose on-line sites that assist scientists in their restriction enzyme work, however, none of these sites meet all the actual needs of laboratory workers, and they do not take into account the enzymes actually present in one's own laboratory.     

Isolation and characterization of polymorphic microsatellite markers for Alternaria alternata

Alternaria alternata is of major significance as a food and feed contaminant and is able to produce a range of mycotoxins that may elicit adverse effects in both animals and humans. We describe the isolation and characterization of five microsatellite markers for studying A. alternata. Marker polymorphism was screened in 64 isolates of A. alternata. The number of alleles per locus ranged from eight to 24, and allelic diversity ranged from 0.425 to 0.882. These markers will be useful in the study of relationships and population genetics amongst isolates of A. alternata.     

Experimental evaluation of environmental enrichment of sea turtles

Although behavioral studies have been conducted at zoos and aquaria for years, documentation concerning the effectiveness of environmental enrichment has dealt primarily with terrestrial animals and marine mammals. Few enrichment studies have been conducted on reptiles. For this study, behavioral observations were made on four captive sea turtles (three loggerhead, Caretta caretta, and one blind green, Chelonia mydas) with enrichment present and absent. Enrichment devices were modified for the special needs of the blind turtle. Behaviors were classified as Resting, Pattern Swimming, Random Swimming, Focused Behavior, Aggression, Hiding, Orientation, and Noncategorized Behavior. It was hypothesized that, when enrichment was present, a decrease in Resting and stereotypic Pattern Swimming would be seen along with an increase in Random Swimming and Focused Behavior. It was found that, when no enrichment devices were present, 77% of the turtles' time was spent in Resting and Pattern Swimming. When enrichment devices were provided, 88% of their time was spent in Random Swimming and Focused Behavior with only 8% spent in Pattern Swimming and Resting. Statistically, there were significant increases in Random Swimming (three of the four turtles) and Focused Behavior (4/4) and significant decreases in Resting (3/4) and Pattern Swimming (3/4) when enrichment devices were present. These results suggest that environmental enrichment is as effective with marine reptiles as has been found with other animals and should be encouraged for all captive sea turtles. Zoo Biol 26:407–416, 2007. © 2007 Wiley‐Liss, Inc.     

Pycnogenol® and vitamin E inhibit ethanol‐induced apoptosis in rat cerebellar granule cells

Pycnogenol® (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol‐induced activation of caspase‐3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 261–271, 2004     

Isolation and characterization of 16 tetranucleotide microsatellite loci in the red panda (Ailurus fulgens)

A total of 15 polymorphic tetranucleotide microsatellite loci in the red panda, Ailurus fulgens, were characterized in this study. Based on evaluations of 33 red pandas, the number of observed alleles for each locus ranged from seven to 17 and the expected and observed heterozygosities were 0.412–0.897 and 0.121–0.909, respectively. The mean polymorphic information content was 0.721. These markers would greatly strengthen the utilization of microsatellite tools in genetic variation studies in red panda populations.     

Rapid and high-throughput analysis of N-glycans from ovarian cancer serum using a 96-well plate platform

We present a rapid and high-throughput human serum N-glycan preparation technology using 96-well plate-based procedures. The released N-glycans from polyvinylidene fluoride (PVDF) membrane filter plate are subsequently loaded to porous graphitic carbon (PGC) containing a 96-well plate to remove salts and other contaminants without sacrificing accuracy or reproducibility. This robust glycan preparation technology is applied to ovarian cancer diagnosis using 5 μl of patient serum.     

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.