The rockefeller university

A full-length cDNA encoding a putative aspartic acid protease (AcAP1) was isolated for the first time from the flesh of pineapple (Ananas comosus) fruit. The deduced sequence of AcAP1 showed all the common features of a typical plant aspartic protease phytepsin precursor. Analysis of AcAP1 gene expression under postharvest chilling treatment in two pineapple varieties differing in their resistance to blackheart development revealed opposite trends. The resistant variety showed an up-regulation of AcAP1 precursor gene expression whereas the susceptible showed a down-regulation in response to postharvest chilling treatment. The same trend was observed regarding specific AP enzyme activity in both varieties. Taken together our results support the involvement of AcAP1 in postharvest chilling stress resistance in pineapple fruits. (C) 2013 Elsevier GmbH. All rights reserved.

Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P-2-degrading enzyme) in the brain and synapses, to Alzheimer disease. Here we report a novel mechanism by which synj1 reversely regulates cellular clearance of amyloid-beta (A beta). Genetic down-regulation of synj1 reduces both extracellular and intracellular A beta levels in N2a cells stably expressing the Swedish mutant of amyloid precursor protein (APP). Moreover, synj1 haploinsufficiency in an Alzheimer disease transgenic mouse model expressing the Swedish mutant APP and the presenilin-1 mutant Delta E9 reduces amyloid plaque load, as well as A beta(40) and A beta(42) levels in hippocampus of 9-month-old animals. Reduced expression of synj1 attenuates cognitive deficits in these transgenic mice. However, reduction of synj1 does not affect levels of full-length APP and the C-terminal fragment, suggesting that A beta generation by beta- and gamma-secretase cleavage is not affected. Instead, synj1 knockdown increases A beta uptake and cellular degradation through accelerated delivery to lysosomes. These effects are partially dependent upon elevated PI(4,5)P-2 with synj1 down-regulation. In summary, our data suggest a novel mechanism by which reduction of a PI(4,5)P-2-degrading enzyme, synj1, improves amyloid-induced neuropathology and behavior deficits through accelerating cellular A beta clearance.

We present a measurement of the production cross section for ZW and ZZ boson pairs in final states with a pair of charged leptons, from the decay of a Z boson, and at least two jets, from the decay of a W or Z boson, using the full sample of proton-antiproton collisions recorded with the CDF II detector at the Tevatron, corresponding to 8.9 fb-1 of integrated luminosity. We increase the sensitivity to vector-boson decays into pairs of quarks using a neural-network discriminant that exploits the differences between the spatial spread of energy depositions and charged-particle momenta contained within the jet of particles originating from quarks and gluons. Additionally, we employ new jet energy corrections to Monte Carlo simulations that account for differences in the observed energy scales for quark and gluon jets. The number of signal events is extracted through a simultaneous fit to the dijet mass spectrum in three classes of events: events likely to contain jets with a heavy-quark decay, events likely to contain jets originating from light quarks, and events that fail these identification criteria. We determine the production cross section to be sigma(ZW+ZZ) = 2.5(-1.0)(+2.0) pb (<6.1 pb at the 95% confidence level), consistent with the standard model prediction of 5.1 pb.

Severe mental illnesses like schizophrenia and bipolar disorder are disabling, chronic conditions that are often accompanied by medical comorbidities. In this theoretical article, we review the allostatic load model representing the "wear and tear" that chronic stress exacts on the brain and body. We propose an innovative way of monitoring physical and psychiatric comorbidities by integrating the allostatic load model into clinical practice. By interpreting peripheral biomarkers differently, medical professionals can calculate a simple, count-based, allostatic load index known to predict diverse stress-related pathologies. In addition to screening for comorbidities, allostatic load indices can be used to monitor the effects of pharmacological and psychosocial interventions. This framework can also be used to generate a dialogue between patient and practitioner to promote preventive and proactive approaches to health care.

The results of a search for the bottomonium counterpart, denoted as X-b, of the exotic charmonium state X(3872) is presented. The analysis is based on a sample of pp collisions at,root s = 8 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 20.7 fb(-1). The search looks for the exclusive decay channel X-b -> Upsilon(1S)pi(+)pi(-) followed by Upsilon(1S) -> mu(+)mu(-). No evidence for an X-b signal is observed. Upper limits are set at the 95% confidence level on the ratio of the inclusive production cross sections times the branching fractions to Upsilon(1S)pi(+)pi(-) of the X-b and the Upsilon(2S). The upper limits on the ratio are in the range 0.9-5.4% for X-b masses between 10 and 11 GeV. These are the first upper limits on the production of a possible X-b at a hadron collider. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.

A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region the basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH prevents stress-induced reductions in AEA and associated increases in BLA dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA CBI (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA. These preclinical findings propose restoring deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to therapeutically mitigate the effects of traumatic stress.

Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stemcells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.

In a previous study we have shown that public buses in Oporto, the second largest city in Portugal, were highly contaminated with MRSA. Here we describe the results of a similar study performed in another urban area of Portugal-Lisbon, the capital. Between May 2011 and May 2012, hand touched surfaces of 199 public buses in Lisbon were screened for MRSA contamination. Subsequently, the hands of 575 passengers who frequently use these bus lines were also screened. All hand carriers of MRSA were further screened for nasal carriage. The isolates were characterized by PFGE, staphylococcal cassette chromosome (SCC) mec typing, spa typing, MLST and were tested for the presence of mecA, Panton-Valentine leukocidin and arginine catabolic mobile element genes. MRSA contamination was shown in 72 buses (36.2%). The majority of the isolates belonged to three major clones: Clone A was identified as EMRSA-15 defined by pattern PFGE A, spa types t2357/t747/t025/t379/t910, ST22, and SCCmec IVh (n=21; 29%). Clone B was the New York/Japan clone characterized by PFGE B-t002/t10682-ST5-II (n=15; 21%). Clone C included isolates with characteristics of the international community-acquired USA300 or related clones, PFGE C-t008-ST8-IVa/IVc/IVg/IVnt/VI (n=19; 26%). The first two clones are currently the two major lineages circulating in Portuguese hospitals. The hands of 15 individuals were contaminated with MRSA belonging to the nosocomial clones A or B. Eleven of these individuals were not nasal carriers of MRSA and all but one had travelled by public transportation, namely by bus, prior to sampling. In conclusion, public buses in two major cities in Portugal are often contaminated with MRSA representing clones dominant in hospitals in the particular geographic area. MRSA contamination of public transport and the transfer of the bacteria to the hands of passengers may represent a route through which hospital-acquired MRSA clones may spread to the community.