Cell numbers and leaf development in Arabidopsis: a functional analysis of the STRUWWELPETER gene

The struwwelpeter (swp) mutant in Arabidopsis shows reduced cell numbers in all aerial organs. In certain cases, this defect is partially compensated by an increase in final cell size. Although the mutation does not affect cell cycle duration in the young primordia, it does influence the window of cell proliferation, as cell number is reduced during the very early stages of primordium initiation and a precocious arrest of cell proliferation occurs. In addition, the mutation also perturbs the shoot apical meristem (SAM), which becomes gradually disorganized. SWP encodes a protein with similarities to subunits of the Mediator complex, required for RNA polymerase II recruitment at target promoters in response to specific activators. To gain further insight into its function, we overexpressed the gene under the control of a constitutive promoter. This interfered again with the moment of cell cycle arrest in the young leaf. Our results suggest that the levels of SWP, besides their role in pattern formation at the meristem, play an important role in defining the duration of cell proliferation.     

Interferons mediate terminal differentiation of human cortical thymic epithelial cells

In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.     

Lipids and sterols in Musca domestica L. (Diptera, Muscidae): changes after treatment with sucrose and lead

Total lipid, fatty acid and sterol composition of larvae and adults of Musca domestica was investigated before and after feeding on sucrose syrup or on the same syrup containing 1% lead nitrate. The effects of sucrose and of lead ions were found to be different. In larvae sucrose diet inhibited the fatty acid elongation and stimulated the first stages of their unsaturation. A significant increase of phytosterol concentrations was obtained. These changes increased the cell membrane permeability. The addition of lead caused a decrease of the fatty acid unsaturation, which decreased the cell membrane permeability. In adults the sucrose diet had no effect on the lipid and sterol composition, while the addition of lead decreased the cholesterol concentration. The composition of lipids and sterols also depends on the diet of larvae before pupation. The data obtained suggested that changes in lipid and sterol composition, which control the permeability of the cell membrane, might be an adaptive response of the organism to the changes of the environment.     

LigBase: a database of families of aligned ligand binding sites in known protein sequences and structures

A database comprising all ligand-binding sites of known structure aligned with all related protein sequences and structures is described. Currently, the database contains approximately 50000 ligand-binding sites for small molecules found in the Protein Data Bank (PDB). The structure-structure alignments are obtained by the Combinatorial Extension (CE) program (Shindyalov and Bourne, Protein Eng., 11, 739-747, 1998) and sequence-structure alignments are extracted from the ModBase database of comparative protein structure models for all known protein sequences (Sanchez et al., Nucleic Acids Res., 28, 250-253, 2000). It is possible to search for binding sites in LigBase by a variety of criteria. LigBase reports summarize ligand data including relevant structural information from the PDB file, such as ligand type and size, and contain links to all related protein sequences in the TrEMBL database. Residues in the binding sites are graphically depicted for comparison with other structurally defined family members. LigBase provides a resource for the analysis of families of related binding sites.     

The Arabidopsis TONNEAU2 gene encodes a putative novel protein phosphatase 2A regulatory subunit essential for the control of the cortical cytoskeleton

In Arabidopsis ton2 mutants, abnormalities of the cortical microtubular cytoskeleton, such as disorganization of the interphase microtubule array and lack of the preprophase band before mitosis, markedly affect cell shape and arrangement as well as overall plant morphology. We present the molecular isolation of the TON2 gene, which is highly conserved in higher plants and has a vertebrate homolog of unknown function. It encodes a protein similar in its C-terminal part to B" regulatory subunits of type 2A protein phosphatases (PP2As). We show that the TON2 protein interacts with an Arabidopsis type A subunit of PP2A in the yeast two-hybrid system and thus likely defines a novel subclass of PP2A subunits that are possibly involved in the control of cytoskeletal structures in plants.     

Photoperiodic Control of Developmental Diapause in Nymphs of Prostriate Ixodid Ticks (Acari: Ixodidae)

Extrinsic control of developmental diapause in nymphs of prostriate ticks of the subgenus Ixodes sensu stricto (Ixodes ricinus and Ixodes persulcatus from Eurasia and Ixodes scapularis from North America) appears to be based on a complex two-step photoperiodic reaction of a short-day/long-day type. Diapause control in the subgenus Afrixodes (the South African tick Ixodes rubicundus) appears to be based on a simple long-day reaction. The option between non-diapause development and diapausing arrest in engorged nymphs is determined by both pre- and post-feeding photoperiodic regimes. Consequently diapausing arrest in engorged nymphs of Ixodes sensu stricto can be induced either by a short-day (after their engorgement) or by a long-day regime (in unfed nymphs), while active, non-diapause development is possible only when the short-day pre-feeding regime is followed by a long-day post-feeding regime. The photoperiodic response in I. (Afrixodes) rubicundus nymphs seems to be of the long-day type both before and after feeding. Consequently this non-diapause development is enabled by a long-day regime, while diapause is induced by a short-day regime of exposure. Nevertheless, there are some indications that the control of nymphal diapause in the latter species is also of a complex nature. This revised version was published online in July 2006 with corrections to the Cover Date.     

A feedforward model of suppressive and facilitatory habituation effects

 Simple exposure to repeatitive stimulation is known to induce short-term learning effects across a wide range of species. These effects can be both suppressive and facilitatory depending on stimulus conditions: repeatitive presentation of a weak stimulus decreases the strength of the response (habituation), whereas presentation of a tonic stimulus following a series of weak stimuli transiently increases the response strength (dishabituation). Although these phenomena have been comprehensively characterized at both behavioral and cellular levels, most existing models of nonassociative learning focus exclusively on the suppressive or facilitatory changes in response, and do not attempt to relate cellular events to behavior. I propose here a feedforward model of habituation effects that explains both suppressive and facilitatory changes in response relying on the interaction between excitatory and inhibitory processes that develop in parallel on two different timescales. The model's properties are used to explain the rate sensitivity property of habituation and recovery and stimulus dishabituation. Received: 1 June 2001 / Accepted in revised form: 4 December 2001     

Effects of simultaneous exercise and loud music on hearing acuity and auditory function

Hearing acuity can be reduced temporarily after exposure to loud noise, and the physiological responses that occur with exercise may enhance this effect. Currently, it is not known whether short-term reductions in hearing acuity after noise exposure and exercise are a result of temporary changes in auditory function. Therefore, the purpose of this investigation was to determine the acute effects of simultaneous exercise and loud music on hearing acuity and auditory function in young, healthy women. Nine women (age = 22 +/- 5 years, body mass index = 23.9 +/- 2.2, Vo(2)peak = 30.6 +/- 6.0 ml x kg(-1) x min(-1)) with normal hearing thresholds (<20 dB hearing level) underwent each of 3 conditions in a randomized counterbalanced design: (a) loud music exposure of 90 to 95 dB sound pressure level for 20 minutes, (b) exercise at 60% Vo(2)peak on a cycle ergometer for 20 minutes, and (c) simultaneous exercise and music exposure for 20 minutes. Hearing acuity and auditory function were assessed via pure-tone hearing thresholds and distortion product otoacoustic emission amplitudes, respectively, at frequencies of 2, 3, 4, 6, and 8 kHz presented in random order before and after each condition. Results indicate that hearing acuity and auditory function remained unaltered after exposure to each condition (p > 0.05). These findings provide evidence that hearing acuity and auditory function in young women do not change after short-term exposure to moderate-intensity exercise and loud music. Thus, listening to loud music with earphones during moderate-intensity exercise does not pose acute hearing health concerns for young physically fit adults with normal hearing.     

The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation

This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed.     

Novel openers of Ca2+-dependent large-conductance potassium channels: symmetrical pharmacophore and electrophysiological evaluation of bisphenols

Electrophysiological evaluation of symmetrical analogues of the known maxi-K opener NS-004 (1) led to the discovery of bisphenols 2a, 3a and 4a as openers of cloned maxi-K channels expressed in oocytes.