289 research outputs found
Avocado
This is a brief guide to growing avocado trees in Hawaii
Mango Cultivars in Hawaii
Mango cultivars grown in Hawaii are discussed
Impaired neural synchrony in the theta frequency range in adolescents at familial risk for schizophrenia
Puberty is a critical period for the maturation of the fronto-limbic and fronto-striate brain circuits responsible for executive function and affective processing. Puberty also coincides with the emergence of the prodromal signs of schizophrenia, which may indicate an association between these two processes.Time-domain analysis and wavelet based time-frequency analysis was performed on electroencephalographic (EEG) data of 30 healthy control (HC) subjects and 24 individuals at familial risk(FR) for schizophrenia. All participants were between the ages of 13 and 18 years and were carefully matched for age, gender, ethnicity, education, andTanner Stage. Electrophysiological recordings were obtained from 32 EEG channels while participants performed a visual oddball task, where they identified rare visual targets among standard "scrambled" images and rare aversive and neutral dis-tracter pictures. The time-domain analysis showed that during target processing the FR group showed smaller event-related potentials in the P2 and P3 range as compared to the HC group. In addition, EEG activity in the theta (4-8 Hz) frequency range was significantly reduced during target processing in the FR group. Inefficient cortical information processing during puberty may be an early indicator of altered brain function in adolescents at FR for schizophrenia and may represent a vulnerability marker for illness onset. Longitudinal assessments will have to determine their predictive value for illness onset in populations at FR for psychotic illness
Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition
The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future
Structures of the Ets Protein DNA-binding Domains of Transcription Factors Etv1, Etv4, Etv5, and Fev: Determinants of DNA Binding and Redox Regulation by Disulfide Bond Formation.
Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation plays a critical role in carcinogenesis. Ets DNA binding, selectivity, and regulation have been extensively studied; however, questions still arise regarding binding specificity outside the core GGA recognition sequence and the mode of action of Ets post-translational modifications. Here, we report the crystal structures of Etv1, Etv4, Etv5, and Fev, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of Etv1, Etv4, and Etv5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism that may control the activity of this subset of oncogenic Ets transcription factors
Structural and dynamical properties of superfluid helium: a density functional approach
We present a novel density functional for liquid 4He, properly accounting for
the static response function and the phonon-roton dispersion in the uniform
liquid. The functional is used to study both structural and dynamical
properties of superfluid helium in various geometries. The equilibrium
properties of the free surface, droplets and films at zero temperature are
calculated. Our predictions agree closely to the results of ab initio Monte
Carlo calculations, when available. The introduction of a phenomenological
velocity dependent interaction, which accounts for backflow effects, is
discussed. The spectrum of the elementary excitations of the free surface and
films is studied.Comment: 37 pages, REVTeX 3.0, figures on request at [email protected]
Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis
Low-Level ionizing radiation induces selective killing of HIV-1-infected cells with reversal of cytokine induction using mtor inhibitors
HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.e., Nef and Tat). HIV-1 reservoirs can be targeted by the “shock and kill” strategy, which utilizes latency-reversing agents (LRAs) to activate latent proviruses and immunotarget the virus-producing cells. Yet, limitations include reduced LRA permeability across anatomical barriers and immune hyper-activation. Ionizing radiation (IR) induces effective viral activation across anatomical barriers. Like other LRAs, IR may cause inflammation and modulate the secretion of extracellular vesicles (EVs). We and others have shown that cells may secrete cytokines and viral proteins in EVs and, therefore, LRAs may contribute to inflammatory EVs. In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-α), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Further, mTORi were found to enhance the selective killing of HIV-1-infected myeloid and T-cell reservoirs at the exclusion of uninfected cells, potentially via inhibition of viral transcription/translation and induction of autophagy. Collectively, the proposed regimen using cART, IR, and mTORi presents a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells
Search for Heavy Neutral and Charged Leptons in e+ e- Annihilation at LEP
A search for exotic unstable neutral and charged heavy leptons as well as for
stable charged heavy leptons is performed with the L3 detector at LEP.
Sequential, vector and mirror natures of heavy leptons are considered. No
evidence for their existence is found and lower limits on their masses are set
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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