The rockefeller university

A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at root s = 8 TeV. The analysis exploits the H -> gamma gamma decay in data corresponding to an integrated luminosity of 19.7 fb(-1) collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities vertical bar eta vertical bar < 2.5, and with the photon of largest and next-to-largest transverse momentum (p(T)(gamma)) divided by the diphoton mass m(gamma gamma) satisfying the respective conditions of p(T)(gamma)/m(gamma gamma) > 1/3 and > 1/4, the total fiducial cross section is 32 +/- 10 fb.

Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human "bomb pulse labeling") for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of "neuroepigenetic" plasticity.

Background Psoriasis vulgaris is an inflammatory immune-mediated disease, with lesional skin characterized by sharply demarcated, erythematous scaly plaques. Uninvolved psoriatic skin appears clinically similar to normal skin. However, it has been hypothesized that inflammatory cytokines, e.g. interleukin (IL)-17, may affect any organ or tissue having a vascular supply; thus, distant uninvolved skin could be exposed to increased circulating IL-17. Objectives To establish comparative genomic profiles between noninvolved skin and normal skin, in particular, determining immune abnormalities in distant uninvolved skin. Methods We performed a meta-analysis on three gene array studies, comparing the nonlesional (NL) psoriatic skin transcriptome with normal gene expression. We investigated immunological features of noninvolved skin, particularly linked to IL-17 signalling. Results We detected 252 differentially expressed gene transcripts in uninvolved skin compared with normal skin; multiple immune-related genes, including IL-17-downstream genes, were upregulated. Increased expression of IL-17-signature genes (e.g. DEFB4 and S100A7) was associated with an increased number of CD3+, CD8+ and DC-LAMP+ cells in NL skin vs. normal controls. Inducible T-cell costimulator (ICOS) expression was detected only in a few T-cells within NL skin. Conclusions Our data described the genomic profile in NL skin, characterizing the immune activation that was mainly attributed to IL-17 signalling.

I applaud Morsella et al.'s approach to investigate consciousness in terms of behavioral control. After all, the function of the brain is to control behavior, and consciousness contributes to the function of the brain. However, I question whether conscious content is available only to the skeletal muscle system, as the principle of parallel responses into skeletal muscle (PRISM) (Morsella 2005) proposes.

The cross-reactivity between some cyclooctynes and thiols limits the bioorthogonality of the strain-promoted azide-alkyne cycloaddition reaction. We show that a low concentration of beta-mercaptoethanol significantly reduces the undesirable side reaction between bicyclononyne (BCN) and cysteine and while preserving free cysteines. We site-specifically label a genetically-encoded azido group in the visual photoreceptor rhodopsin to demonstrate the utility of the strategy.

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.

In most chemokine receptors, one or multiple tyrosine residues have been identified within the receptor N-terminal domain that are, at least partially, modified by posttranslational tyrosine sulfation. For example, tyrosine sulfation has been demonstrated for Tyr-3, -10, -14, and -15 of CCR5, for Tyr-3, -14, and -15 of CCR8, and for Tyr-7, -12, and -21 of CXCR4. While there is evidence for several chemokine receptors that tyrosine sulfation is required for optimal interaction with the chemokine ligands, the precise role of tyrosine sulfation for chemokine receptor function remains unclear. Furthermore, the function of the chemokine receptor N-terminal domain in chemokine binding and receptor activation is also not well understood. Sulfotyrosine peptides corresponding to the chemokine receptor N-termini are valuable tools to address these important questions both in structural and functional studies. However, due to the lability of the sulfotyrosine modification, these peptides are difficult to obtain using standard peptide chemistry methods. In this chapter, we provide methods to prepare sulfotyrosine peptides by enzymatic in vitro sulfation of peptides using purified recombinant tyrosylprotein sulfotransferase (TPST) enzymes. In addition, we also discuss alternative approaches for the generation of sulfotyrosine peptides and methods for sulfopeptide analysis.

Non-fibrillar soluble oligomeric forms of amyloid-beta peptide (oA beta) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oA beta initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of A beta, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oA beta levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oA beta to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and A beta on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with A beta and tau pathology.

BACKGROUND: Pain is the most common complication of Sickle Cell Disease (SCD). Tissue oximetry properties in SCD during steady state and acute pain are not well described. METHODS: This was a cross sectional study of tissue oximetry properties in individuals with SCD during steady state, acute pain and healthy controls without SCD. A novel tissue oximetry device was used to better account for tissue pigmentation interference. We hypothesized that during acute SCD pain, blood volume to painful areas would be at least 10% less than steady state. Bayesian analyses of the data (with flat piors) were planned a priori because of the small projected sample size. RESULTS: The sample included 14 individuals (4 during crisis, 5 steady state, and 5 controls). In individuals with SCD, blood volume to the lower back was higher during crisis (0.18% of tissue volume vs. 0.14%). Bayesian analyses yielded a 3% probability that our hypothesis (that blood volume would decrease by 10%) was correct. CONCLUSIONS: During acute SCD pain, blood volume to painful areas is not decreased. Bayesian analyses were useful for interpretation of small sample data and may have utility in early phase trials for rare diseases.