Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity.

Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases.

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

Background: Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood.

Objective: In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function.

Accumulation of neural activity in the posterior insula encodes the passage of time.

A number of studies have examined the perception of time with durations ranging from milliseconds to a few seconds, however the neural basis of these processes are still poorly understood and the neural substrates underlying the perception of multiple-second intervals are unknown. Here we present evidence of neural systems activity in circumscribed areas of the human brain involved in the encoding of intervals with durations of 9 and 18s in a temporal reproduction task using event-related functional magnetic resonance imaging (fMRI). During the encoding there was greater activation in more posterior parts of the medial frontal and insular cortex whereas the reproduction phase involved more anterior parts of these brain structures.

Anterior insular cortex anticipates impending stimulus significance.

Touch is a fundamental, but complex, element of everyday interaction that impacts one's sensory and affective experience via interoceptive processing. The insular cortex is an integral component of the neural processes involved in interoception, i.e.

Location, location: using functional magnetic resonance imaging to pinpoint brain differences relevant to stimulant use.

Aims: The purpose of this review is to summarize the neural substrate dysfunctions and disrupted cognitive, affective and experiential processes observed in methamphetamine and cocaine-dependent individuals.

Methods: We reviewed all publications in PubMed that conducted comparison studies between healthy volunteers and cocaine-, amphetamine- or methamphetamine-dependent individuals using functional magnetic resonance imaging.

Results: Stimulant dependence is characterized by a distributed alteration of functional activation to a number of experimental paradigms.

Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein.

Depsipeptide is in clinical trials for chronic lymphocytic leukemia (CLL) on the basis of earlier observations demonstrating selective in vitro activity in CLL. We sought to determine the relationship of histone H3 and H4 acetylation, inhibition of histone deacetylase, and apoptosis observed in CLL cells to justify a pharmacodynamic end point in these clinical trials. We demonstrate that in vitro depsipeptide induces histone H3 and H4 acetylation and histone deacetylase enzyme inhibition at concentrations corresponding to the LC50 (concentration producing 50% cell death) for cultured CLL cells (0.

The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction.

Rituximab is a chimeric monoclonal antibody directed at CD20 with significant activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). A variety of pathways of tumor cytotoxicity different from cytotoxic chemotherapy have been proposed for this therapeutic antibody including antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. This report describes that a proportion of patients with CLL receiving rituximab treatment have in vivo activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage in blood leukemia cells immediately following infusion of rituximab.