The rockefeller university

Social recognition manifests itself in decreased investigation of a previously encountered individual. Estrogen receptor alpha (ER alpha) knock out mice show deficient social recognition and anxiety. These data show that the ER alpha is involved in these effects, but they do not say anything about the brain sites important for these effects. In this study, an shRNA encoded within an AAV viral vector directed against the ER alpha receptor gene (or containing luciferase control), was injected bilaterally into the posterodorsal amygdala (MePDA) or the ventromedial nucleus of the hypothalamus (VMN) of female rats. An 81% reduction of ER alpha expression in the MePDA eliminated social recognition. Moreover, this diminution of ER alpha in the MePDA reduced anxiety in the light/dark choice test. In contrast, social recognition was unaffected after ERa knockdown in the VMN while aggressiveness against the juvenile was enhanced. In conclusion, social recognition and anxiety in female rats are modulated by the ER alpha in the amygdala. Moreover, aggression against juveniles but not against adults could, at least partly, depend on the ER alpha in the VMN. (C) 2010 Elsevier B.V. All rights reserved.

We report measurements of the polarization of W bosons from top-quark decays using 2.7 fb(-1) of p (p) over bar collisions collected by the CDF II detector. Assuming a top-quark mass of 175 GeV/c(2), three measurements are performed. A simultaneous measurement of the fraction of longitudinal (f(0)) and right-handed (f(0)) W bosons yields the model- independent results f(0) =0. 88 +/- 0.11(stat) +/- 0.06(syst) and f(+) = 0.15 +/- 0.07(stat) +/- 0.06(syst) with a correlation coefficient of -0.59. A measurement of f(0) [f(+)] constraining f(+) [f(0)] to its standard model value of 0.0 [0.7] yields f(0) 0.70 + 0.07(stat) +/- 0.04(syst) [f(+) - 0.01 +/- 0.02(stat) +/- 0.05(syst)]. All these results are consistent with standard model expectations. We achieve the single most precise measurements of f(0) for both the model- independent and modeldependent determinations.

Post-translational modification of histones provides an important regulatory platform for processes such as gene transcription and DNA damage repair. It has become increasingly apparent that the misregulation of histone modification, which is caused by the deregulation of factors that mediate the modification installation, removal and/or interpretation, actively contributes to human cancer. In this Review, we summarize recent advances in understanding the interpretation of certain histone methylations by plant homeodomain finger-containing proteins, and how misreading, miswriting and mis-erasing of histone methylation marks can be associated with oncogenesis and progression. These observations provide us with a greater mechanistic understanding of epigenetic alterations in human cancers and might also help direct new therapeutic interventions in the future.

This composite article is intended to give the experts in the field of cochlear mechanics an opportunity to voice their personal opinion on the one mechanism they believe dominates cochlear amplification in mammals. A collection of these ideas are presented here for the auditory community and others interested in the cochlear amplifier. Each expert has given their own personal view on the topic and at the end of their commentary they have suggested several experiments that would be required for the decisive mechanism underlying the cochlear amplifier. These experiments are presently lacking but if successfully performed would have an enormous impact on our understanding of the cochlear amplifier. (C) 2010 Elsevier B.V. All rights reserved.

The glycolipid alpha-galactosylceramide (alpha-GalCer) has been shown to bind CD1d molecules to activate invariant natural killer T (iNKT) cells, and subsequently induce activation of various immune-competent cells, including dendritic cells, thereby providing a significant adjuvant effect for various vaccines. However, in phase I clinical trials, alpha-GalCer was shown to display only marginal biological activity. In our search for a glycolipid that can exert more potent stimulatory activity against iNKT cells and dendritic cells and produce an adjuvant effect superior to alpha-GalCer, we performed step-wise screening assays on a focused library of 25 alpha-GalCer analogues. Assays included quantification of the magnitude of stimulatory activity against human iNKT cells in vitro, binding affinity to human and murine CD1d molecules, and binding affinity to the invariant t cell receptor of human iNKT cells. Through this rigorous and iterative screening process, we have identified a lead candidate glycolipid, 7DW8-5, that exhibits a superior adjuvant effect than alpha-GalCer on HIV and malaria vaccines in mice.

Psoriasis is now classified as an immune-mediated inflammatory disease ( IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.

Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when pi-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations.

Sindbis virus (SINV) is the prototype member of the Alphavirus genus, whose members cause severe human diseases for which there is no specific treatment. To ascertain host factors important in the replication of the SINV RNA genome, we generated a SINV expressing nsP4, the viral RNA-dependent RNA polymerase, with an in-frame 3 x Flag epitope tag. Proteomic analysis of nsP4-containing complexes isolated from cells infected with the tagged virus revealed 29 associated host proteins. Of these, 10 proteins were associated only at a later time of infection (12 h), 14 were associated both early and late, and five were isolated only at the earlier time (6 h postinfection). These results demonstrate the dynamic nature of the virus-host interaction that occurs over the course of infection and suggest that different host proteins may be required for the multiple functions carried out by nsP4. Two related proteins found in association with nsP4 at both times of infection, GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) and G3BP2 were also previously identified as associated with SINV nsP2 and nsP3. We demonstrate a likely overlapping role for these host factors in limiting SINV replication events. The present study also identifies 10 host factors associated with nsP4 6 h after infection that were not found to be associated with nsP2 or nsP3. These factors are candidates for playing important roles in the RNA replication process. Identifying host factors essential for replication should lead to new strategies to interrupt alphavirus replication.

This study employs a voice-transformation to overcome the limitations of brain mapping to study brain representations of natural sounds such as speech. Brain mapping studies of natural sound representations, which present a fixed sound to many neurons with different acoustic frequency selectivity, are difficult to interpret because individual neurons exhibit considerable unexplained variability in the dynamical aspects of their evoked responses. This new approach samples how a single recording responds to an ensemble of sounds, instead of sampling an ensemble of neuronal recordings. A noise excited filter-bank analysis and resynthesis vocoder systematically shifts the frequency band occupied by sounds in the ensemble. The quality of the voice transformation is assessed by evaluating the number of bands the filter bank must have to support emotional prosody identification. Perceptual data show that emotional prosody can be recognized within normal limits if the bandwidth of filter-bank channels is less than or equal to the bandwidth of perceptual auditory filters. Example physiological data show that stationary linear transfer functions cannot fully explain the responses of central auditory neurons to speech sounds, and that deviations from model predictions are not random. They may be related to acoustic or articulatory features of speech.

A study reports a new method for wholesale labeling of neuronal proteins in situ that can visualize newly synthesized protein in a manner compatible with standard immunostaining techniques.