A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion

A human CD2 cytoplasmic tail-binding protein, termed CD2BP1, was identified by an interaction trap cloning method. Expression of CD2BP1 is restricted to hematopoietic tissue, being prominent in T and natural killer (NK) cells, with long (CD2BP1L) and short (CD2BP1S) variants arising by alternative RNA splicing. Both CD2BP1 molecules are homologous to Schizosaccharomyces pombe cdc15, and include a helical domain, variable length intervening PEST sequence and C-terminal SH3 domain. Although the CD2BP1 SH3 domain binds directly to the CD2 sequence, KGPPLPRPRV (amino acids 300-309), its association is augmented markedly by the CD2BP1 N-terminal segment. Upon ligand-induced clustering of surface CD2 molecules, CD2BP1 redistributes from a cytosolic to a surface membrane compartment, co-localizing with CD2. In turn, CD2-stimulated adhesion is downregulated by CD2BP1, apparently through coupling of the protein tyrosine phosphatase (PTP)-PEST to CD2. These findings offer the first molecular view into the control processes for T cell adhesion.     

Measurement of the ultrasonic attenuation of fat at high frequency

RATIONALE AND OBJECTIVES: High-frequency ultrasound devices are often limited by a decreased depth of acoustic imaging caused by the increased attenuation of tissue at high frequencies. We investigated the role of adipose tissue in this phenomenon. METHODS: A substitution technique was used to calculate the ultrasonic attenuation (decibels per centimeter) of fresh samples of sheep rumen, omental fat, and back fat and swine back fat and various concentrations of bovine milk fat at 22 degrees C and 37 degrees C for frequencies of 15 and 20 MHz. RESULTS: The attenuation was significantly higher for sheep adipose tissue than for the intestinal wall, in descending order, omental fat, back fat, and rumen wall (P < 0.01). A correlation was found between bovine milk fat concentrations and attenuation at both frequencies (R2 > 0.9). The attenuation of adipose tissues decreased significantly with an increase in temperature (P < 0.01), whereas the attenuation of sheep rumen showed no significant change (P > 0.1). CONCLUSIONS: The ultrasonic attenuation of fat may contribute to limitations on the use of high-frequency ultrasound in clinical situations in which adipose tissue is present.     

An animal model of hypoxia-induced perinatal seizures

Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.     

NMR determination of the major solution conformation of a peptoid pentamer with chiral side chains

Polymers of N-substituted glycines ("peptoids") containing chiral centers at the alpha position of their side chains can form stable structures in solution. We studied a prototypical peptoid, consisting of five para-substituted (S)-N-(1-phenylethyl)glycine residues, by NMR spectroscopy. Multiple configurational isomers were observed, but because of extensive signal overlap, only the major isomer containing all cis-amide bonds was examined in detail. The NMR data for this molecule, in conjunction with previous CD spectroscopic results, indicate that the major species in methanol is a right-handed helix with cis-amide bonds. The periodicity of the helix is three residues per turn, with a pitch of approximately 6 A. This conformation is similar to that anticipated by computational studies of a chiral peptoid octamer. The helical repeat orients the amide bond chromophores in a manner consistent with the intensity of the CD signal exhibited by this molecule. Many other chiral polypeptoids have similar CD spectra, suggesting that a whole family of peptoids containing chiral side chains is capable of adopting this secondary structure motif. Taken together, our experimental and theoretical studies of the structural properties of chiral peptoids lay the groundwork for the rational design of more complex polypeptoid molecules, with a variety of applications, ranging from nanostructures to nonviral gene delivery systems.     

Poor elimination rates in waste water treatment plants lead to continuous emission of deoxynivalenol into the aquatic environment

Deoxynivalenol (DON) is one of the most prominent mycotoxins generated by fungi of the generus Fusarium on crops. Its presence in surface waters was recently demonstrated. Here, we elucidate the occurrence and behaviour of DON in three Swiss waste water treatment plants (WWTP) as a result of human consumption and excretion. DON was shown to be omnipresent in the primary effluent samples of these WWTP in concentrations from 32 to 118 ng/L. Corresponding loads were a factor of 1.3–2.3 higher than predicted based on human excretion data from the literature. DON elimination rates in WWTP ranged from 33 to 57%. These rather low percentages were confirmed with a further, more detailled study conducted at WWTP Kloten/Opfikon (average elimination rate 32%). The relative importance of WWTP as a source of DON in surface waters was compared with agricultural emissions due to runoff from Fusarium infected crops. Both sources seem to contribute equally to the total DON exposure of surface waters of a few ng/L, however, their input dynamics vary considerably in space and time.     

Control of coccidiosis: lessons from other sporozoa

Coccidiosis is the most important parasitic infection in poultry worldwide and also causes problems in cattle, sheep and goats. Control is largely limited to good husbandry and prophylactic chemotherapy using a range of drugs against which resistance is rapidly acquired. Attempts at vaccination using conventional vaccines have been disappointing and there is now a need for a new approach. Research into the immunology of coccidiosis has lagged behind that of other sporozoans and there are useful lessons that might be learned from studies on toxoplasmosis, cryptosporidiosis, theileriosis and malaria. In these infections the emphasis has turned to the cytokine network that drives the response towards protection. Central to these studies are the roles of interferon-gamma, interleukin-12 and activated macrophages with the involvement of nitric oxide in parasite killing. Cytotoxic T cells have also increasingly been implicated. Research has shown that different immune responses can be elicited by manipulating the cytokine system and these new concepts can be applied to the design of peptide or recombinant vaccines, and the possibilities of developing such vaccines against coccidiosis will be discussed.