The influence of transcranial direct current stimulation to the trigeminal nerve on attention and arousal.

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC.

Robust method for chromatogram shape analysis to improve early detection of performance drifts and adverse changes in process parameters during purification column operations.

The biopharmaceutical industry is under increased pressure to maximize efficiency, enhance quality compliance, and reduce the cost of drug substance manufacturing. Ways to reduce costs associated with manufacturing of complex biological molecules include maximizing efficiency of chromatography purification steps. For example, process analytical technology (PAT) tools can be employed to improve column resin life, prevent column operating failures, and decrease the time it takes to solve investigations of process deviations.

Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain. The LC-NA system is believed to regulate arousal and attention and is a pharmacological target in multiple clinical conditions. Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans.

Testing locus coeruleus-norepinephrine accounts of working memory, attention control, and fluid intelligence.

The current set of studies examined the relationship among working memory capacity, attention control, fluid intelligence, and pupillary correlates of tonic arousal regulation and phasic responsiveness in a combined sample of more than 1,000 participants in two different age ranges (young adults and adolescents). Each study was designed to test predictions made by two recent theories regarding the role of the locus coeruleus-norepinephrine (LC-NE) system in determining individual differences in cognitive ability. The first theory, proposed by Unsworth and Robison (2017a), posits two important individual differences: the moment-to-moment regulation of tonic arousal, and the phasic responsiveness of the system to goal-relevant stimuli.

The impact of divided attention on automatic postural responses: A systematic review and meta-analysis.

Quick responses to a loss of balance or "automatic postural responses" (APRs) are critical for fall prevention. The addition of a distracting task- dual-tasking (DT), typically worsens performance on mobility tasks. However, the effect of DT on APRs is unclear.

Insight into the Influence of the Chiral Molecular Symmetry on the Chiroptics of Fluorescent BINOL-Based Boron Chelates.

The prominent influence of the molecular symmetry, as defined by the symmetry point group, on the chiroptical behavior (electronic circular dichroism and, especially, circularly polarized luminescence) of simple fluorescent boron chelates (BODIPY and related BOPHY analogues) is studied and discussed. It is shown that increasing the dye symmetry by means of the chiral symmetry group is a workable design option to enhance the level of differential emission of right- and left-circularly polarized light in BODIPY dyes and related emitters, and that the influence of the level of symmetry is stronger than the influence of the higher number of chiral moieties perturbing the acting achiral chromophore.

Synthesis and Chiroptical Properties of Hexa-, Octa-, and Deca-azaborahelicenes: Influence of Helicene Size and of the Number of Boron Atoms.

Four members of a new class of cycloborylated hexa-, octa-, and deca-helicenes (1 a-d) have been prepared in enantiopure form, along with two cycloplatinated deca-helicenes (1 d', 1 d ), further extending the family of cycloplatinated hexa- and octa-helicenes reported previously. The azabora[n]helicenes display intense electronic circular dichroism and large optical rotations; the dependence of the optical activity on the size of the helix (n=6, 8, 10) and the number of boron atoms (1 or 2) has been examined in detail both experimentally and theoretically. The photophysical properties (nonpolarized and circularly polarized luminescence) of these new fluorescent organic helicenes have been measured and compared with the corresponding organometallic phosphorescent cycloplatinated derivatives (1 a -d ).

Nanowell-based immunoassays for measuring single-cell secretion: characterization of transport and surface binding.

Arrays of subnanoliter wells (nanowells) provide a useful system to isolate single cells and analyze their secreted proteins. Two general approaches have emerged: one that uses open arrays and local capture of secreted proteins, and a second (called microengraving) that relies on closed arrays to capture secreted proteins on a solid substrate, which is subsequently removed from the array. However, the design and operating parameters for efficient capture from these two approaches to analyze single-cell secretion have not been extensively considered.

A new toolbox for assessing single cells.

Unprecedented access to the biology of single cells is now feasible, enabled by recent technological advancements that allow us to manipulate and measure sparse samples and achieve a new level of resolution in space and time. This review focuses on advances in tools to study single cells for specific areas of biology. We examine both mature and nascent techniques to study single cells at the genomics, transcriptomics, and proteomics level.

In vivo discovery of immunotherapy targets in the tumour microenvironment.

Recent clinical trials showed that targeting of inhibitory receptors on T cells induces durable responses in a subset of cancer patients, despite advanced disease. However, the regulatory switches controlling T-cell function in immunosuppressive tumours are not well understood. Here we show that such inhibitory mechanisms can be systematically discovered in the tumour microenvironment.

Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells.

Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days.

Paclitaxel delivery to brain tumors from hydrogels: a computational study.

Malignant gliomas are aggressive forms of primary brain tumors characterized by a poor prognosis. The most successful treatment so far is the local implantation of polymer carriers (Gliadel® wafers) for the sustained release of carmustine. To improve the effectiveness of local drug treatment, new polymer carriers and pharmacological agents are currently being investigated.

Micropatterned ligand arrays to study spatial regulation in Fc receptor signaling.

Fc receptor signaling plays a fundamental role in immune responses. A plethora of Fc -receptors (e.g.

Ca2+ waves initiate antigen-stimulated Ca2+ responses in mast cells.

Ca(2+) mobilization is central to many cellular processes, including stimulated exocytosis and cytokine production in mast cells. Using single cell stimulation by IgE-specific Ag and high-speed imaging of conventional or genetically encoded Ca(2+) sensors in rat basophilic leukemia and bone marrow-derived rat mast cells, we observe Ca(2+) waves that originate most frequently from the tips of extended cell protrusions, as well as Ca(2+) oscillations throughout the cell that usually follow the initiating Ca(2+) wave. In contrast, Ag conjugated to the tip of a micropipette stimulates local, repetitive Ca(2+) puffs at the region of cell contact.

F-actin and myosin II accelerate catecholamine release from chromaffin granules.

The roles of nonmuscle myosin II and cortical actin filaments in chromaffin granule exocytosis were studied by confocal fluorescence microscopy, amperometry, and cell-attached capacitance measurements. Fluorescence imaging indicated decreased mobility of granules near the plasma membrane following inhibition of myosin II function with blebbistatin. Slower fusion pore expansion rates and longer fusion pore lifetimes were observed after inhibition of actin polymerization using cytochalasin D.

Focal adhesion proteins connect IgE receptors to the cytoskeleton as revealed by micropatterned ligand arrays.

Patterned surfaces that present specific ligands in spatially defined arrays are used to examine structural linkages between clustered IgE receptors (IgE-Fc epsilonRI) and the cytoskeleton in rat basophilic leukemia (RBL) mast cells. We showed with fluorescence microscopy that cytoskeletal F-actin concentrates in the same regions as cell surface IgE-Fc epsilonRI that bind to the micrometer-size patterned ligands. However, the proteins mediating these cytoskeletal connections and their functional relevance were not known.

Nanobiotechnology and cell biology: micro- and nanofabricated surfaces to investigate receptor-mediated signaling.

Advances in microfabrication and nanofabrication are opening new opportunities to investigate complicated questions of cell biology in ways not before possible. In particular, the spatial regulation of cellular processes can be examined by engineering the chemical and physical environment to which the cell responds. Lithographic methods and selective chemical modification schemes can provide biocompatible surfaces that control cellular interactions on the micron and submicron scales on which cells are organized.