Laser-Driven Anharmonic Oscillator: Ground-State Dissociation of the Helium Hydride Molecular Ion by Midinfrared Pulses.

The vibrational motion of molecules represents a fundamental example of an anharmonic oscillator. Using a prototype molecular system, HeH^{+}, we demonstrate that appropriate laser pulses make it possible to drive the nuclear motion in the anharmonic potential of the electronic ground state, increasing its energy above the potential barrier and facilitating dissociation by purely vibrational excitation. We find excellent agreement between the frequency-dependent response of the helium hydride molecular cation to both classical and quantum mechanical simulations, thus removing any ambiguities through electronic excitation.

TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis.

The activity of the SMN complex in promoting the assembly of pre-mRNA processing UsnRNPs correlates with condensation of the complex in nuclear Cajal bodies. While mechanistic details of its activity have been elucidated, the molecular basis for condensation remains unclear. High SMN complex phosphorylation suggests extensive regulation.

Heteronuclear Limit of Strong-Field Ionization: Fragmentation of HeH^{+} by Intense Ultrashort Laser Pulses.

The laser-induced fragmentation dynamics of this most fundamental polar molecule HeH^{+} are measured using an ion beam of helium hydride and an isotopologue at various wavelengths and intensities. In contrast to the prevailing interpretation of strong-field fragmentation, in which stretching of the molecule results primarily from laser-induced electronic excitation, experiment and theory for nonionizing dissociation, single ionization, and double ionization both show that the direct vibrational excitation plays the decisive role here. We are able to reconstruct fragmentation pathways and determine the times at which each ionization step occurs as well as the bond length evolution before the electron removal.

Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells.

Genetic variation in the leucine-rich repeat kinase 2 (LRRK2) gene is associated with risk of familial and sporadic Parkinson's disease (PD). To support clinical development of LRRK2 inhibitors as disease-modifying treatment in PD biomarkers for kinase activity, target engagement and kinase inhibition are prerequisite tools. In a combined proteomics and phosphoproteomics study on human peripheral mononuclear blood cells (PBMCs) treated with the LRRK2 inhibitor Lu AF58786 a number of putative biomarkers were identified.

The shape of things to come in speech production: Visual form interference during lexical access.

Naming a picture is slower in categorically related compared with unrelated contexts, an effect termed semantic interference. This effect has informed the development of all contemporary models of lexical access in speech production. However, category members typically share visual features, so semantic interference might in part reflect this confound.

Polyglutamine expansion of ataxin-3 alters its degree of ubiquitination and phosphorylation at specific sites.

Ubiquitination and phosphorylation of proteins represent post translational modifications (PTMs) capable of regulating a variety of cellular processes. In the neurodegenerative disorder spinocerebellar ataxia type 3 (SCA3), the disease causing protein ataxin-3 carries an expanded polyglutamine (polyQ) stretch causing it to aggregate in nuclear inclusions. These inclusions are decorated with ubiquitin suggestive of a malfunction in the clearance of the mutant protein.

Modulation of microsaccades by spatial frequency during object categorization.

The organization of visual processing into a coarse-to-fine information processing based on the spatial frequency properties of the input forms an important facet of the object recognition process. During visual object categorization tasks, microsaccades occur frequently. One potential functional role of these eye movements is to resolve high spatial frequency information.

Planning sentences while doing other things at the same time: effects of concurrent verbal and visuospatial working memory load.

This study investigated to what extent advance planning during sentence production is affected by a concurrent cognitive load. In two picture-word interference experiments in which participants produced subject-verb-object sentences while ignoring auditory distractor words, we assessed advance planning at a phonological (lexeme) and at an abstract-lexical (lemma) level under visuospatial or verbal working memory (WM) load. At the phonological level, subject and object nouns were found to be activated before speech onset with concurrent visuospatial WM load, but only subject nouns were found to be activated with concurrent verbal WM load, indicating a reduced planning scope as a function of type of WM load (Experiment 1).

On the costs of parallel processing in dual-task performance: The case of lexical processing in word production.

Previous dual-task picture-naming studies suggest that lexical processes require capacity-limited processes and prevent other tasks to be carried out in parallel. However, studies involving the processing of multiple pictures suggest that parallel lexical processing is possible. The present study investigated the specific costs that may arise when such parallel processing occurs.

Phosphoregulation of the human SMN complex.

The survival motor neuron (SMN) complex is a macromolecular machine comprising 9 core proteins: SMN, Gemins2-8 and unrip in vertebrates. It performs tasks in RNA metabolism including the cytoplasmic assembly of spliceosomal small nuclear ribonucleoprotein particles (snRNPs). The SMN complex also localizes to the nucleus, where it accumulates in Cajal Bodies (CB) and may function in transcription and/or pre-mRNA splicing.

Comparison of SILAC and mTRAQ quantification for phosphoproteomics on a quadrupole orbitrap mass spectrometer.

Advances in mass spectrometric methodology and instrumentation have promoted a continuous increase in analytical performance in the field of phosphoproteomics. Here, we employed the recently introduced quadrupole Orbitrap (Q Exactive) mass spectrometer for quantitative signaling analysis to a depth of more than 15 000 phosphorylation sites. In parallel to the commonly used SILAC approach, we evaluated the nonisobaric chemical labeling reagent mTRAQ as an alternative quantification technique.

Resolving competition when naming an object in a multiple-object display.

Naming an object in the context of other objects requires the selection and processing of the target object at different levels, while the processing of competing representations activated by context objects has to be constrained. At what stage are these competing representations attenuated? To address this question, we presented pairs of target and context objects that were either similar in visual shape (e.g.

Activation of phonological competitors in visual search.

Recently, Meyer, Belke, Telling and Humphreys (2007) reported that competitor objects with homophonous names (e.g., boy) interfere with identifying a target object (e.

Phosphosignature predicts dasatinib response in non-small cell lung cancer.

Targeted drugs are less toxic than traditional chemotherapeutic therapies; however, the proportion of patients that benefit from these drugs is often smaller. A marker that confidently predicts patient response to a specific therapy would allow an individual therapy selection most likely to benefit the patient. Here, we used quantitative mass spectrometry to globally profile the basal phosphoproteome of a panel of non-small cell lung cancer cell lines.

Combination of chemical genetics and phosphoproteomics for kinase signaling analysis enables confident identification of cellular downstream targets.

Delineation of phosphorylation-based signaling networks requires reliable data about the underlying cellular kinase-substrate interactions. We report a chemical genetics and quantitative phosphoproteomics approach that encompasses cellular kinase activation in combination with comparative replicate mass spectrometry analyses of cells expressing either inhibitor-sensitive or resistant kinase variant. We applied this workflow to Plk1 (Polo-like kinase 1) in mitotic cells and induced cellular Plk1 activity by wash-out of the bulky kinase inhibitor 3-MB-PP1, which targets a mutant kinase version with an enlarged catalytic pocket while not interfering with wild-type Plk1.

The rapid extraction of gist-early neural correlates of high-level visual processing.

The human cognitive system is highly efficient in extracting information from our visual environment. This efficiency is based on acquired knowledge that guides our attention toward relevant events and promotes the recognition of individual objects as they appear in visual scenes. The experience-based representation of such knowledge contains not only information about the individual objects but also about relations between them, such as the typical context in which individual objects co-occur.

Ease of processing constrains the activation flow in the conceptual-lexical system during speech planning.

In 3 picture-word interference experiments, speakers named a target object in the presence of an unrelated not-to-be-named context object. Distractor words, which were phonologically related or unrelated to the context object's name, were used to determine whether the context object had become phonologically activated. All objects had high frequency names, and the ease of processing of these objects was manipulated by a visual degradation technique.

Is there semantic interference in delayed naming?

The semantic interference effect in the picture-word interference task is interpreted as an index of lexical competition in prominent speech production models. Janssen, Schirm, Mahon, and Caramazza (2008) challenged this interpretation on the basis of experiments with a novel version of this task, which introduced a task-switching component. Participants either named the picture or read the word, depending on the word's color.

Proteomics analysis of cellular imatinib targets and their candidate downstream effectors.

Inhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Knowledge about direct cellular targets of kinase-selective drugs and the identification of druggable downstream mediators of oncogenic signaling are relevant for both initial therapy selection and the nomination of alternative targets in case molecular resistance emerges. To address these issues, we performed a proof-of-concept proteomics study designed to monitor drug effects on the pharmacologically tractable subproteome isolated by affinity purification with immobilized, nonselective kinase inhibitors.

Quantitative analysis of kinase-proximal signaling in lipopolysaccharide-induced innate immune response.

The innate immune system senses invariant microbial components via toll-like receptors (TLRs) to elicit a host defense program against invading pathogens. Lipopolysaccharide (LPS), a constituent of Gram-negative bacteria, is recognized by TLR4 and triggers protein kinase signaling to orchestrate immune responses such as inflammatory cytokine production. To analyze kinase-proximal signaling in murine macrophages, we performed prefractionation experiments with immobilized kinase inhibitors to enrich for protein kinases and their interaction partners.

Semantic relatedness among objects promotes the activation of multiple phonological codes during object naming.

In a picture-word interference experiment the authors demonstrate that a semantic-categorical relation between a to-be-named target picture and a context picture promotes the phonological activation of the to-be-ignored context picture. No such phonological activation is observed if the objects are semantically unrelated. This finding gives further insight into the mechanisms that modulate the activation flow in the conceptual-lexical system during speech planning.

Large-scale proteomics analysis of the human kinome.

Members of the human protein kinase superfamily are the major regulatory enzymes involved in the activity control of eukaryotic signal transduction pathways. As protein kinases reside at the nodes of phosphorylation-based signal transmission, comprehensive analysis of their cellular expression and site-specific phosphorylation can provide important insights into the architecture and functionality of signaling networks. However, in global proteome studies, low cellular abundance of protein kinases often results in rather minor peptide species that are occluded by a vast excess of peptides from other cellular proteins.

Do perceived context pictures automatically activate their phonological code?

Morsella and Miozzo (Morsella, E., & Miozzo, M. (2002).