Towards an improved understanding of eta --> gamma^* gamma^*

We argue that high-quality data on the reaction $e^+e^-\to \pi^+\pi^-\eta$ will allow one to determine the double off-shell form factor $\eta \to \gamma^*\gamma^*$ in a model-independent way with controlled accuracy. This is an important step towards a reliable evaluation of the hadronic light-by-light scattering contribution to the anomalous magnetic moment of the muon. When analyzing the existing data for $e^+e^- \to \pi^+\pi^-\eta$ in the range of total energies $1\text{GeV}^2<Q_2^2<(4.5\text{GeV})^2$, we demonstrate that the double off-shell form factor $F_{\eta\gamma^*\gamma^*}(Q_1^2,Q_2^2)$ is consistent with the commonly employed factorization ansatz at least for $Q_1^2<1\text{GeV}^2$, if the effect of the $a_2$ meson is taken into account. However, better data are needed to draw firm conclusions.Comment: 7 pages, 3 figure

IP6K3 and IPMK variations in LOAD and longevity: evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein–protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits

Foix-Chavany-Marie syndrome in a 17-year-old female with congenital cytomegalovirus infection.

Foix-Chavany-Marie syndrome is characterized by bilateral facio-glosso-pharyngo-masticatory paralysis of voluntary movement due to bilateral anterior opercular lesions. We describe the case of a 17-year-old female affected by Foix-Chavany-Marie syndrome and congenital cytomegalovirus infection, evaluating the possible etiopathogenetic correlation between cerebral cortical dysplasia and intrauterine infections

National surveillance for human and pet contact with oral rabies vaccine baits, 2001–2009

Objective—To determine the rate and absolute number of human and pet exposures to oral rabies vaccine (ORV) bait containing liquid vaccinia rabies glycoprotein recombinant vaccine and to evaluate factors that might affect human contact with bait to modify the program and reduce human exposure to the vaccine. Design—Retrospective analysis of surveillance data (2001 to 2009). Sample—Reports on human and pet contact with ORV baits in states with ORV surveillance programs. Procedures—Data were collected from passive, multistate ORV surveillance systems in Alabama, Arizona, Florida, Georgia, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Tennessee, Texas, Vermont, Virginia, and West Virginia. Data collected included the nature of human or pet contact with bait and vaccine, the caller’s knowledge of the ORV bait program, local human population density, and other relevant demographic data. Results—All 18 states participated in the surveillance program for at least 1 year, for a combined 68 years of observation. One thousand four hundred thirty-six calls were reported, representing 3,076 found baits (6.89/100,000 baits dropped); 296 (20%) calls were related to human contact with ruptured bait, and 550 (38%) involved pet contact with the bait. Six adverse events in humans were reported, one of which required hospitalization. Fifty-nine adverse events in pets were noted, all of which were nonserious. Conclusions and Clinical Relevance—Findings from surveillance activities have been used to improve baiting strategies and minimize human and pet contact with ORV baits. Overall, human and pet contact with ORV baits was infrequent. Surveillance has led to early identification of persons exposed to ORV and rapid intervention

The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy.

Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence. TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL). The association of TERT SNPs with longevity remains uncertain and varies with ethnicity. The aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity. METHODS: MNS16A genotypes have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals 88 years old (>91 years old). TL was assessed using genomic DNA from whole blood of 72 selected individuals by a multiplex real-time PCR assay. RESULTS: MNS16A appears associated to longevity, showing significant associations in Comparison 2 (Age Class 3 vs. Age Class 2) under both additive (odds ratio [O.R.] 0.749; p=0.019) and dominant (O.R. 0.579; p=0.011) models. The MNS16A*L allele is significantly underrepresented in Age Class 3 (O.R. 0.759; p=0.020) compared to Age Class 2. A significant telomere attrition is reported along the three age classes (p=0.0001), that remains significant only in L*/L* genotype carriers (p=0.002) when the analysis was conducted according to MNS16A genotype. CONCLUSIONS: The TERT MNS16A*L allele appears negatively associated with longevity. The concomitant significant telomere cross sectional attrition rate observed for L*/L* genotype suggests that this polymorphism could influence human longevity by affecting TL

LRP1-Mediated AggLDL Endocytosis Promotes Cholesteryl Ester Accumulation and Impairs Insulin Response in HL-1 Cells

The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis

Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases.ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. (C) 2012 Elsevier Inc. All rights reserved