Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

ERRATUM: "FERMI DETECTION OF γ-RAY EMISSION FROM THE M2 SOFT X-RAY FLARE ON 2010 JUNE 12" (2012, ApJ, 745, 144)

Due to an error at the publisher, the times given for the major tick marks in the X-axis in Figure 1 of the published article are incorrect. The correctly labeled times should be "00:52:00," "00:54:00," ... , and "01:04:00." The correct version of Figure 1 and its caption is shown below. IOP Publishing sincerely regrets this error

Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2-Derived Cytokines Interleukin-4 and Interleukin-5

Activation and recruitment of eosinophils in allergic inflammation is in part mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However, little is known concerning the signal transduction mechanisms by which this activation occurs. We have investigated tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the p21ras-ERK signaling pathway in human eosinophils. The related cytokines interleukin- 3 (IL-3), IL-5, and granulocyte-macrophage colonystimulating factor (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine- associated PI3K activity. Protein kinase B (PKB) is a downstream target of PI3K activation by growth factors. Induction of PKB phosphorylation in human eosinophils was transiently induced on activation with the cytokines IL-4 and IL-5, as well as the chemoattractants PAF, C5a, and RANTES showing a broad activation profile. Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44ERK1 and p42ERK2, showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF. Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5 and PAF-primed eosinophils. In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions

Does Race Matter in Landowners ' Participation in Conservation Incentive Programs?

Tl1i.s study ir~vestigcitcd cmd conlpclred the participatiori hclimvior of'ivhite uncl nrinoritj~ sriicrll Iandowner: ~ iri Aleibcrrnu ir ~ eight corzservutiorz iricentive progrirrils. Usirig norprurnetric tests irnd logit niodeling, rt~cfounrll?ot11 sin~ilrrities anrl clflercrzces irz purticipulion heliuvior betiveen these rrvo lcrricloivner groups. Both ivhite emd liiiriority Irnclorcners tc.rirk.d rio t lo purl icipcrte in con.sert~alion iricer? t ive progrrmr.~, crricl were eyucrl/y likely to participate it2 tlre overall progrur7u, Conservcrtiorz Reserve Progrmrn (CRP), Stewurdship l~icerzrivrs Progranz (SIP), crnd Forestr ~ It?c'entives Progruriz (FIP). White lczrido~i.ners, hoivcver, ir'ere erirollecl iri the CRP lotlgcr cine / signed up niore crcres iti the CRP cmcl FIP tliciri r~ziriorities. Morc.ovc.r, mir~orilies,+,ere rizorc likck to be clissutisfied ivith progreznl pcrrtir.ipatiori riricl to bc IAIIU~/CJ to c!lfi)rd th