An RsaI polymorphism in the transcribed region of the neurofibromatosis (NF1)-gene

We describe an RsaI polymorphism in the transcribed region (exon 5) of the neurofibromatosis type 1 (NF1)-gene     

The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis

TACC3 is a centrosomal/mitotic spindle-associated protein that is highly expressed in a cell cycle-dependent manner in hematopoietic lineage cells. During embryonic development, TACC3 is expressed in a variety of tissues in addition to the hematopoietic lineages. TACC3 deficiency causes an embryonic lethality at mid- to late gestation involving several lineages of cells. Hematopoietic stem cells, while capable of terminal differentiation, are unable to be expanded in vitro or in vivo in reconstitution approaches. Although gross alterations in centrosome numbers and chromosomal segregation are not observed, TACC3 deficiency is associated with a high rate of apoptosis and expression of the p53 target gene, p21(Waf1/Cip1). Hematopoietic stem cell functions, as well as deficiencies in other cell lineages, can be rescued by combining the TACC3 deficiency with p53 deficiency. The results support the concept that TACC3 is a critical component of the centrosome/mitotic spindle apparatus and its absence triggers p53-mediated apoptosis.     

PR-39, a potent neutrophil inhibitor, attenuates myocardial ischemia-reperfusion injury in mice

We investigated the effects of PR-39, a recently discovered neutrophil inhibitor, in a murine model of myocardial ischemia-reperfusion injury. Mice were given an intravenous injection of vehicle (n = 12) or PR-39 (n = 9) and subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion. In addition, the effects of PR-39 on leukocyte rolling and adhesion were studied utilizing intravital microscopy of the rat mesentery. The area-at-risk per left ventricle was similar in vehicle- and PR-39-treated mice. However, myocardial infarct per risk area was significantly (P < 0.01) reduced in PR-39 treated hearts (21.0 +/- 3.8%) compared with vehicle (47.1 +/- 4.8%). Histological analysis of ischemic reperfused myocardium demonstrated a significant (P < 0.01) reduction in polymorphonuclear neutrophil (PMN) accumulation in PR-39-treated hearts (n = 6, 34.3 +/- 1.7 PMN/mm(2)) compared with vehicle-treated myocardium (n = 6, 59.7 +/- 3.1 PMN/mm(2)). In addition, PR-39 significantly (P < 0.05) attenuated leukocyte rolling and adherence in rat inflamed mesentery. These results indicate that PR-39 inhibits leukocyte recruitment into inflamed tissue and attenuated myocardial reperfusion injury in a murine model of myocardial ischemia-reperfusion.     

Inactivation of a subpopulation of human neutrophils by exposure to ultrahigh-molecular-weight polyethylene wear debris

Polymorphonuclear neutrophils, a first line of defence against invading microbial pathogens, may be attracted by inflammatory mediators triggered by ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles released from orthopaedic prostheses. Phagocytosis of UHMWPE particles by neutrophils may indirectly compromise their phagocytic-bactericidal mechanisms, thus enhancing host susceptibility to microbial infections. In an in vitro assay, pre-exposure of purified human neutrophils to UHMWPE micrometre- and submicrometre-sized wear particles interfered with subsequent Staphylococcos aureus uptake in a heterogeneous way, as assessed by a dual label fluorescence microscopic assay that discriminated intracellular rhodamine-labelled UHMWPE particles from fluorescein isothiocyanate-labelled S. aureus. Indeed, a higher percentage (44%) of neutrophils having engulfed UHMWPE particles lost the ability to phagocytize S. aureus, compared with UHMWPE-free neutrophils (<3%). Pre-exposure of neutrophils to UHMWPE wear particles did not impair but rather stimulated their oxidative burst response in a chemoluminescence assay. The presence of UHMWPE wear particles did not lead to significant overall consumption of complement-mediated opsonic factors nor decreased surface membrane display of neutrophil complement receptors. In conclusion, engulfment of UHMWPE wear particles led to inactivation of S. aureus uptake in nearly half of the neutrophil population, which may potentially impair host clearance mechanisms against pyogenic infections.     

The Semiotic Body

Most bodies in this world do not have brains and the minority of animal species that do have brained bodies are descendents from species with more distributed or decentralized nervous systems. Thus, bodies were here first, and only relatively late in evolution did the bodies of a few species grow supplementary organs, brains, sophisticated enough to support a psychological life. Psychological life therefore from the beginning was embedded in and served as a tool for corporeal life. This paper discusses the semiotically controlled dynamics of bodily existence that has allowed the evolution of these seemingly ‘unnatural’ mental and even linguistic kinds of species. It is shown how the skin, on the one hand, makes us belong in the world, and on the other hand, is part of the huge landscape of membranes across which the semiotic self incessantly must be reconstituted. The discussion moves on to the intracellular world of signal transduction through which the activity of single cells are put to service for bodily needs. The paper further considers the mechanisms behind homeostasis and the semiotics of the psycho-neuro-endocrine integration in the body. The concept of semiotic emergence is introduced and a holistic marker hypothesis for why some animals may have an experiential life is suggested.

Contribution of planktonic and detritic fractions to the natural diet of mesozooplankton in Bahía Blanca Estuary

The pike, Esox lucius Linnaeus, is a predatory fish that supports important fisheries and could substantially impact prey populations around the temperate northern hemisphere. Consumption of prey by pike is most readily estimated using the energy budget to calculate food intake indirectly using estimates of growth rate and metabolism. Resting metabolic rate, R _s, is a particularly important component of such calculations. Here, the available estimates of R _s are reviewed and compared. Scaling coefficients for variation with body mass are consistent between the two studies in which they have been derived (0.81, 0.82). However, the effect of temperature on R _s markedly varies among studies (Q ₁₀ from 1.73 to 4.80). There is substantial variation in R _s (twofold to fourfold) among studies when temperature and fish size are accounted for. This variation is shown to have a large effect on energy budget calculations of energy intake and to be sufficient to account for imbalances in published budgets. These effects depend on age of pike and season; in one energy budget model, a 50% reduction in R _s resulted in decrease of 19–42% in estimated energy intake of pike. Potential causes of among-study variation in R _s are discussed and it is recommended that standard techniques by applied in the future to differentiate between genuine biological variation among populations and experimental factors. Guest editors: J. M. Farrell, C. Skov, M. Mingelbier, T. Margenau & J. E. Cooper International Pike Symposium: Merging Knowledge of Ecology, Biology, and Management for a Circumpolar Species     

MRI-based assessment of hip joint translations

To better understand movement limitations and, to some extent, the pathogenesis of osteoarthritis, it is important to quantitatively measure femoroacetabular translations to assess if any joint subluxation occurs. In this paper, we aim at measuring hip joint displacements from magnetic resonance images (MRI) based on a surface registration technique. Because this measurement is related to the location of the hip joint center (HJC), we investigate and compare different HJC estimation approaches based on patient-specific 3D bone models. We estimate the HJC based on a simulated circumduction while minimizing inter-articular distance changes. Measurements of femoroacetabular translations during low amplitude abductions ($80$ samples) and extreme flexions ($60$ samples) in female professional dancers, which is a population potentially exposed to femoroactebaluar impingements, do not show any significant subluxation.     

BMI and Severity of Clinical and Radiographic Signs of Hip Osteoarthritis

Obesity might be involved in the pathogenesis of osteoarthritis (OA) not only via increased mechanical loading, but also via an inflammatory component possibly causing increased pain and functional disability. The study aim was to examine the relationship between BMI and clinical symptoms as well as radiographic severity of OA in patients scheduled for primary total hip arthroplasty (THA). We conducted a cross‐sectional study of 855 patients scheduled for a first THA for primary OA at a single centre between November 2001 and December 2006. The primary outcome was clinical and radiographic severity of OA, which was evaluated in four BMI categories (18.5–24.9, 25–29.9, 30–34.9 and ≥35 kg/m²). We used the Harris Hip Score (HHS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) to assess pain and function. The severity of radiographic hip joint damage was evaluated using the Kellgren–Lawrence classification. Multivariate analyses were performed to adjust for potential confounders. In patients scheduled for THA, increasing BMI was associated with significantly higher levels of pain and functional disability on both HHS (P for trend <0.001) and WOMAC (P for trend <0.001). However, the degree of radiographic joint damage remained similar across BMI categories. These findings emphasize the need to further investigate the potential pathogenic role of obesity and low‐grade inflammation in OA and underscore the importance of obesity prevention to avoid early prosthetic replacement of the hip.