Human frontal eye fields and spatial priming of pop-out.

"Priming of pop-out" is a form of implicit memory that facilitates detection of a recently inspected search target. Repeated presentation of a target's features or its spatial position improves detection speed (feature/spatial priming). This study investigated a role for the human frontal eye fields (FEFs) in the priming of color pop-out.

Object naming is a more sensitive measure of speech localization than number counting: Converging evidence from direct cortical stimulation and fMRI.

Using direct cortical stimulation to map language function during awake craniotomy is a well-described and useful technique. However, the optimum neuropsychological tasks to use have not been detailed. We used both functional MRI (fMRI) and direct cortical stimulation to compare the sensitivity of two behavioral paradigms, number counting and object naming, in the demonstration of eloquent cortical language areas.

Integrated image- and function-guided surgery in eloquent cortex: a technique report.

The ability to effectively identify eloquent cortex in close proximity to brain tumours is a critical component of surgical planning prior to resection. The use of electrocortical stimulation testing (ECS) during awake neurosurgical procedures remains the gold standard for mapping functional areas, yet the preoperative use of non-invasive brain imaging techniques such as fMRI are gaining popularity as supplemental surgical planning tools. In addition, the intraoperative three-dimensional display of fMRI findings co-registered to structural imaging data maximizes the utility of the preoperative mapping for the surgeon.

Functionally specific reorganization in human premotor cortex.

After unilateral stroke, the dorsal premotor cortex (PMd) in the intact hemisphere is often more active during movement of an affected limb. Whether this contributes to motor recovery is unclear. Functional magnetic resonance imaging (fMRI) was used to investigate short-term reorganization in right PMd after transcranial magnetic stimulation (TMS) disrupted the dominant left PMd, which is specialized for action selection.

The Yersinia effector protein YpkA induces apoptosis independently of actin depolymerization.

The pathogenicity of the plague agent Yersinia pestis is largely due to the injection of effector proteins that potently block immune responses into host cells through a type III secretion apparatus. One Yersinia effector protein, YpkA, a putative serine/threonine kinase, has been reported to act by depolymerizing actin and disrupting actin microfilament organization. Using YpkA-GFP fusion proteins to directly visualize cells expressing YpkA, we found instead that YpkA triggered rapid cell death that can be blocked by caspase inhibitors and Bcl-xL, but was not dependent on caspase-8.

STAT5 isoforms: controversies and clarifications.

STAT (signal transducer and activator of transcription) family transcription factors are critical regulators of the development and differentiation of many cell types. STAT isoforms are generated by alternative splicing, but have also been suggested to be generated post-transcriptionally. In this issue of the Biochemical Journal, Schuster and colleagues have identified cathepsin G as the protease that cleaves full-length STAT5 (STAT5alpha) to generate a C-terminally truncated form in immature myeloid cells.

Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development.

Ewing sarcoma gene EWS encodes a putative RNA-binding protein with proposed roles in transcription and splicing, but its physiological role in vivo remains undefined. Here, we have generated Ews-deficient mice and demonstrated that EWS is required for the completion of B cell development and meiosis. Analysis of Ews(-/-) lymphocytes revealed a cell-autonomous defect in precursor B lymphocyte (pre-B lymphocyte) development.

Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation.

Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset.

Electrospray deposition of carbon nanotubes in vacuum.

Here we report on a novel and effective technique for the deposition of carbon nanotubes onto surfaces in vacuum directly from a liquid suspension. The technique, based on in-vacuum electrospray ionization, has the potential to bridge the gap between high resolution techniques requiring ultra-high vacuum conditions, and non-volatile molecules and nanostructures such as carbon nanotubes. Atomic force microscopy of double-walled nanotubes deposited onto silicon surfaces in vacuum show individual nanotubes and low density bundles.

Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals.

Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common gamma chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6.

Nonredundant roles for Stat5a/b in directly regulating Foxp3.

Stats (signal transducers and activators of transcription) regulate multiple aspects of T-cell fate. T regulatory (Treg) cells are a critical subset that limits immune responses, but the relative importance of Stat5a/b versus Stat3 for Treg cell development has been contentious. We observed that peripheral CD25(+)CD4(+) T cells were reduced in Stat5(DeltaN) mice; however, the levels of Foxp3, a transcription factor that is critical for Treg cells, were normal in splenic CD4(+) T cells even though they were reduced in the thymus.

Complementary effects of thienopyridine pretreatment and platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention; results from the ESPRIT trial.

Objectives: This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention.

Background: Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited.

Methods: We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial.

Opioid dependence.

Introduction: Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state, such as craving and mood, and independent of circumstances, such as finance, and physical location.

T cell-directed therapies: lessons learned and future prospects.

Agents interfering with T cell function are therapeutic mainstays for various autoimmune diseases and for transplant approaches to organ failure. The understanding of T cell biology has blossomed since the development of most agents now in use. Here we discuss T cell-specific agents now in use, others recently added to the therapeutic armamentarium and promising agents being investigated in clinical and preclinical studies.

Human tyk2 kinase deficiency: another primary immunodeficiency syndrome.

Janus kinases are critical for cytokine signaling. Mutations of Jak3 cause primary immunodeficiency, but Minegishi et al. (2006) now show that mutation of another Jak, tyrosine kinase 2, underlies another human immunodeficiency syndrome.

Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

Objective: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC).

Design: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications.

Results: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis.

Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiation.

Cybr (also known as Cytip, CASP, and PSCDBP) is an interleukin-12-induced gene expressed exclusively in hematopoietic cells and tissues that associates with Arf guanine nucleotide exchange factors known as cytohesins. Cybr levels are dynamically regulated during T-cell development in the thymus and upon activation of peripheral T cells. In addition, Cybr is induced in activated dendritic cells and has been reported to regulate dendritic cell (DC)-T-cell adhesion.

Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system.

Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T(H)-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3.

Square, hexagonal, and row phases of PTCDA and PTCDI on Ag-Si(111)square root(3) x square root(3)R30 degrees.

We have investigated the ordered phases of the perylene derivatives perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride (PTCDA) and the imide analogue PTCDI on the Ag-Si(111)square root(3) x square root(3)R30 degrees surface using scanning tunneling microscopy. We find that PTCDA forms square, hexagonal, and herringbone phases, which coexist on the surface. The existence of a square phase on a hexagonal surface is of particular interest and is a result of a near commensurability between the molecular dimensions and the surface lattice.

Functional MRI of memory in the hippocampus: Laterality indices may be more meaningful if calculated from whole voxel distributions.

Lateralization of memory by functional MRI (fMRI) may be helpful for surgical planning related to the medial temporal lobe (MTL). Most fMRI memory studies have calculated lateralization indices (LI) in the MTL from suprathreshold voxels only, but the selection of threshold remains highly arbitrary. We hypothesized that LIs could be reliably extracted from the distribution of voxels encompassing all positive T statistical values, each weighted by their own statistical significance.

Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells.

Suppressor of cytokine signaling (Socs) 3 is a cytokine-inducible inhibitor with critical but selective cell-specific effects. We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, Socs3 had no effect on IL-12-dependent signal transducer and activator of transcription (Stat) 4 phosphorylation or IL-4-dependent Stat6 phosphorylation. By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters.