Insulin-like growth factor (IGF) binding protein-4 is both a positive and negative regulator of IGF activity in vivo.

IGFs are required for normal prenatal and postnatal growth. Although actions of IGFs can be modulated by a family of IGF-binding proteins (IGFBPs) in vitro, these studies have identified a complicated pattern of stimulatory and inhibitory IGFBP effects, so that understanding relevant aspects of IGFBP action in vivo has been limited. Here we have produced a null mutation of one specific IGFBP, IGFBP-4, which is coexpressed with IGF-II early in development.

The concept of template-based de novo design from drug-derived molecular fragments and its application to TAR RNA.

Principles of fragment-based molecular design are presented and discussed in the context of de novo drug design. The underlying idea is to dissect known drug molecules in fragments by straightforward pseudo-retro-synthesis. The resulting building blocks are then used for automated assembly of new molecules.

Extracellular point mutations in FGFR2 result in elevated ERK1/2 activation and perturbation of neuronal differentiation.

Two independent gain-of-function point mutations (S252W and P253R) in the extracellular region of the FGFR2 (fibroblast growth factor receptor 2) increase the binding affinity for the growth factor. The effect of this enhanced growth factor binding by these mutants is expected to be an increase in activation of regular signalling pathways from FGFR2 as a result of more receptors being engaged by ligand at any given time. Using PC12 (pheochromocytoma) cells as a model cell system we investigated the effect of these mutations on protein phosphorylation including the receptor, the activation of downstream signalling pathways and cell differentiation.

Global profiling of phosphopeptides by titania affinity enrichment.

Protein phosphorylation is a ubiquitous post-translational modification critical to many cellular processes. Large-scale unbiased characterization of phosphorylation status remains a major technical challenge in proteomics. In the present work, we evaluate and optimize titania-based affinity enrichment for global profiling of phosphopeptides from complex biological mixtures.

Estradiol attenuates hyperoxia-induced cell death in the developing white matter.

Objective: Periventricular leukomalacia is the predominant type of brain injury in preterm infants underlying the development of cerebral palsy. Periventricular leukomalacia has its peak incidence at 23 to 32 weeks postconceptional age characterized by extensive oligodendrocyte migration and maturation. Oxygen toxicity has been identified as a possible contributing factor to the pathogenesis of cerebral palsy in survivors of preterm birth.

Molecular query language (MQL)--a context-free grammar for substructure matching.

We have developed a Java library for substructure matching that features easy-to-read syntax and extensibility. This molecular query language (MQL) is grounded on a context-free grammar, which allows for straightforward modification and extension. The formal description of MQL is provided in this paper.

Diffraction of fast atomic projectiles during grazing scattering from a LiF(001) surface.

Light atoms and molecules with energies from 300 eV to 25 keV are scattered under a grazing angle of incidence from a LiF(001) surface. For impact of neutral projectiles along low index directions for strings of atoms in the surface plane we observe a defined pattern of intensity spots in the angular distribution of reflected particles which is consistently described using concepts of diffraction theory and specific features of grazing scattering of atoms from insulator surfaces. Experimental results for scattering of H, D, 3He, and 4He atoms as well as H2 and D2 molecules can be unequivocally referred to atom diffraction with de Broglie wavelengths as low as about 0.

Delayed mammary gland involution in mice with mutation of the insulin-like growth factor binding protein 5 gene.

IGFs (IGF-I and IGF-II) are essential for development, and their bioactivities are tightly regulated by six related IGF-binding proteins (IGFBPs). IGFBP-5 is the most highly conserved binding protein and is expressed in several key developmental lineages as well as in multiple adult tissues including the mammary gland. To explore IGFBP-5 actions in vivo, we produced IGFBP-5 knockout (KO) mice.

Electrocortical reflections of face and gaze processing in children with pervasive developmental disorder.

Background: Children with pervasive developmental disorder (PDD) show behavioral abnormalities in gaze and face processing, but recent studies have indicated that normal activation of face-specific brain areas in response to faces is possible in this group. It is not clear whether the brain activity related to gaze processing is also normal in children with PDD.

Methods: Event-related brain potentials (ERPs) were measured during two spatial attention tasks in which a centrally presented stimulus served as cue for the location of a forthcoming target.

[Trends in oral healthcare. Caries prevalence and frequency of visits to the dentist for checkups].

In 2003 the project 'Changes in oral health and preventive behaviour'was carried out for the sixth time in succession in The Netherlands. Children and adolescents were asked to fill out a questionnaire and to participate in an oral health examination. Compared to the 1996/1997 results 9-year-olds had a lower incidence of FS and DMFS, 14-year-olds had a higher incidence of DS, and 20-year-olds had a larger number of DS and a smaller number of FS, DMFS and DMFT in 2003.

A pseudo-ligand approach to virtual screening.

A virtual screening method is presented that is grounded on a receptor-derived pharmacophore model termed "virtual ligand" or "pseudo-ligand". The model represents an idealized constellation of potential ligand sites that interact with residues of the binding pocket. For rapid virtual screening of compound libraries the potential pharmacophore points of the virtual ligand are encoded as an alignment-free correlation vector, avoiding spatial alignment of pharmacophore features between the pharmacophore query (i.

A family of auxin conjugate hydrolases from Brassica rapa: characterization and expression during clubroot disease.

During the obligate biotrophic interaction of Plasmodiophora brassicae with members of the Brassicaceae, the host roots show hypertrophy and galls are established. An increased auxin pool appears to correlate with cell expansion and cell division, but the origin of the free auxin is not yet clear. As previous results point to increased IAA-hydrolytic activity in infected roots of Brassica rapa at later time points of infection, we isolated IAA-amidohydrolase-like genes from various tissues.

Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5.

IGF-I and IGF-II are essential regulators of mammalian growth, development and metabolism, whose actions are modified by six high-affinity IGF binding proteins (IGFBPs). New lines of knockout (KO) mice lacking either IGFBP-3, -4, or -5 had no apparent deficiencies in growth or metabolism beyond a modest growth impairment (approximately 85-90% of wild type) when IGFBP-4 was eliminated. To continue to address the roles of these proteins in whole animal physiology, we generated combinational IGFBP KO mice.

Transcriptome analysis of Arabidopsis clubroots indicate a key role for cytokinins in disease development.

The clubroot disease of the family Brassicaceae is caused by the obligate biotrophic protist Plasmodiophora brassicae. Infected roots undergo a developmental switch that results in the formation of aberrant roots (clubs). To investigate host gene expression during the development of the disease, we have used the Arabidopsis ATH1 genome array.

Maturation-dependent oligodendrocyte apoptosis caused by hyperoxia.

In the immature human brain, periventricular leukomalacia (PVL) is the predominant white matter injury underlying the development of cerebral palsy. PVL has its peak incidence during a well-defined period in human brain development (23-32 weeks postconceptional age) characterized by extensive oligodendrocyte migration and maturation. We hypothesized that the dramatic rise of oxygen tissue tension associated with mammalian birth and additional oxygen exposure of the preterm infant during intensive care may be harmful to immature oligodendrocytes (OLs).

[Oral health care in nursing and old people's homes and institutions for the mentally handicapped].

Staff members and residents of nursing homes and old people's homes were interviewed about the facilities and provision of oral health care. Clinical examinations were performed to obtain data about the oral health status of the institutionalised elderly. Results show that in most cases the oral health care facilities were insufficient to give care to persons with natural teeth.

[Direct access to the dental hygienist 2. Opinions of dental hygienists and dentists].

In this paper the opinions from dental hygienists and dentists are described concerning the question whether patients could visit the dental hygienist without being seen by a dentist first (access without referral). Eight of ten dental hygienists have a positive attitude towards the idea of access without referral. Dentists were much more sceptical about this idea.

[Direct access to the dental hygienist 1. Opinions of relevant national organizations].

The opinions of professional dental organisations, the government (Ministry of Health), patient organizations and the medical assurance companies are collected on the question whether patients could visit the dental hygienist without being seen by a dentist first. The general opinion is that this could be possible for those treatments for which the dental hygienist are fully qualified. However, the professional organizations of the dentists claim that the dentist should always be responsible for the patient register and thereby the first responsible for the dental health of the patients.

Spatial attention triggered by eye gaze enhances and speeds up visual processing in upper and lower visual fields beyond early striate visual processing.

Objective: The detection of a lateralized visual target is faster when preceded by a face gazing to the location of this stimulus. Here we aimed to clarify the time-course of the visual processing modulated by these reflexive shifts of attention.

Methods: ERPs were measured on 16 subjects performing a speeded location task on a circular checkerboard.

The changing impact of a severe disaster on the mental health and substance misuse of adolescents: follow-up of a controlled study.

Background: Disasters are believed to have large effects on the mental health of adolescents but the lack of prospective pre- and post-disaster data on affected and control populations have limited our knowledge on the validity of these claims. We examined the medium-term, 12 months' effects of a severe disaster on the mental health of adolescents, and compared them to effects after 5 months.

Method: A café fire in The Netherlands injured 250 adolescents and killed 14.

Degradation of microvascular brain endothelial cell beta-catenin after co-culture with activated neutrophils from patients undergoing cardiac surgery with prolonged cardiopulmonary bypass.

The adhesion of highly activated neutrophils to cerebral microvascular endothelial cells (MVECs) may contribute to disruption and hyperpermeability of the blood-brain barrier (BBB) after cardiac surgery with prolonged cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil-mediated BBB damage has not been investigated on the cellular level yet. Therefore, we studied the effects of neutrophils from cardiac surgery patients with CPB time <80 min (group I; n=8) and >80 min (group II; n=8) on the integrity of cultured porcine MVEC.