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Memory and Plasticity

Episodic memory of APOE ?4 carriers is correlated with fractional anisotropy, but not cortical thickness, in the medial temporal lobe.

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Episodic memory of APOE ?4 carriers is correlated with fractional anisotropy, but not cortical thickness, in the medial temporal lobe.

Neuroimage. 2012 Jul 10;63(1):507-516

Authors: Westlye ET, Hodneland E, Haász J, Espeseth T, Lundervold A, Lundervold AJ

Abstract
The ?4 allele of apolipoprotein E (apoE, protein; APOE, gene) is the most important genetic risk factor for the development of Alzheimer's disease (AD). Cortical structures in the medial temporal lobe (MTL) are important for memory function and are affected early in AD. Both gray matter (GM) and white matter (WM) structures in the MTL have been reported to display AD related changes in healthy APOE ?4 carriers, but the effects are relatively small and somewhat deviating. Still, there is a lack of studies directly linking structural measures with performance on psychometric tests in ?4+ individuals. We hypothesized that intact WM integrity in the MTL facilitates episodic memory, and predicted a higher correlation between WM integrity and memory performance in APOE ?4 carriers due to a possible limiting effect of WM microstructure. In the present study of 92 healthy (MMSE>27) participants we acquired T1 3D and DTI images from a 1.5T MRI scanner, and tested the participants with California Verbal Learning Test II (CVLT-II). The study had two main aims: 1) to relate verbal memory performance to entorhinal WM (EWM) integrity in APOE ?4 carriers and non-carriers, and 2) to investigate APOE ?4 effects on EWM and EC thickness. We observed a strong, positive correlation between FA in the EWM and memory performance, which was driven solely by APOE ?4 carriers. These effects were significant while controlling for age, sex, EWM volume and EC thickness. Although EC thickness was significantly reduced in ?4 carriers, we did not find a relationship between EC thickness and memory performance. Thus, increased susceptibility of the WM structures underpinning the entorhinal-hippocampal network, offers a plausible explanation for the earlier onset of cognitive decline previously reported in APOE ?4 carriers.

PMID: 22796460 [PubMed - as supplied by publisher]


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Escherichia coli: great diversity around a common core.

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Escherichia coli: great diversity around a common core.

MBio. 2012;3(3)

Authors: Moriel DG, Rosini R, Seib KL, Serino L, Pizza M, Rappuoli R

Abstract
Escherichia coli outbreak in Germany, which resulted in more than 4,000 cases, including 908 cases of hemolytic-uremic syndrome (HUS) and at least 50 deaths, highlighted the genome plasticity of E. coli and the potential for new virulent strains to emerge. The analysis of 170 E. coli genome sequences for the presence of nine previously identified protective extraintestinal pathogenic E. coli antigens suggested the feasibility of a combination vaccine as a universal intervention against all pathogenic E. coli strains. IMPORTANCE: This article reports on the feasibility of a combination vaccine as a universal intervention against all pathogenic Escherichia coli strains.

PMID: 22669628 [PubMed - in process]


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Inner hair cells of mice express the glutamine transporter SAT1.

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Inner hair cells of mice express the glutamine transporter SAT1.

Hear Res. 2012 Jul 25;

Authors: Oguchi T, Suzuki N, Hashimoto S, Chaudhry GA, Chaudhry FA, Usami SI, Ottersen OP

Abstract
Glutamate has been implicated in signal transmission between inner hair cells and afferent fibers of the organ of Corti. The inner hair cells are enriched in glutamate and the postsynaptic membranes express AMPA glutamate receptors. However, it is not known whether inner hair cells contain a mechanism for glutamate replenishment. Such a mechanism must be in place to sustain glutamate neurotransmission. Here we provide RT-PCR and immunofluorescence data indicating that system A transporter 1 (SLC38A1), which is associated with neuronal glutamine transport and synthesis of the neurotransmitters GABA and glutamate in CNS, is expressed in inner hair cells. It was previously shown that inner hair cells contain glutaminase that converts glutamine to glutamate. Thus, our finding that inner hair cells express a glutamine transporter and the key glutamine metabolizing enzyme glutaminase, provides a mechanism for glutamate replenishment and bolsters the idea that glutamate serves as a transmitter in the peripheral synapse of the auditory system.

PMID: 22841570 [PubMed - as supplied by publisher]


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Molecular and Clinical Aspects of Angelman Syndrome.

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Molecular and Clinical Aspects of Angelman Syndrome.

Mol Syndromol. 2012 Apr;2(3-5):100-112

Authors: Dagli A, Buiting K, Williams CA

Abstract
The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2-q13 genomic region identifies 75-80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5-10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity.

PMID: 22670133 [PubMed - as supplied by publisher]


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Regulation of Allergic Responses to Chemicals and Drugs: Possible Roles of Epigenetic Mechanisms.

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Regulation of Allergic Responses to Chemicals and Drugs: Possible Roles of Epigenetic Mechanisms.

Toxicol Sci. 2012 Jun 15;

Authors: Moggs J, Terranova R, Kammueller M, Chibout SD, Chapman V, Dearman RJ, Kimber I

Abstract
There is increasing evidence that epigenetic regulation of gene expression plays a pivotal role in the orchestration of immune and allergic responses. Such regulatory mechanisms have potentially important implications for the acquisition of sensitization to chemical and drug allergens, and in determining the vigor, characteristics and longevity of allergic responses. Importantly, the discovery of long-lasting epigenetic alterations in specific immunoregulatory genes provides a mechanistic basis for immune cell memory, and thereby the potential of chemical allergens to influence the subsequent orientation of the adaptive immune system. In this article we consider the implications of epigenetic mechanisms for the development of sensitization to chemical and drug allergens and the form that allergic reactions will take.

PMID: 22705809 [PubMed - as supplied by publisher]


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