Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

A Model for the Ultrastructure of Bone Based on Electron Microscopy of Ion-Milled Sections

The relationship between the mineral component of bone and associated collagen has been a matter of continued dispute. We use transmission electron microscopy (TEM) of cryogenically ion milled sections of fully-mineralized cortical bone to study the spatial and topological relationship between mineral and collagen. We observe that hydroxyapatite (HA) occurs largely as elongated plate-like structures which are external to and oriented parallel to the collagen fibrils. Dark field images suggest that the structures (“mineral structures”) are polycrystalline. They are approximately 5 nm thick, 70 nm wide and several hundred nm long. Using energy-dispersive X-ray analysis we show that approximately 70% of the HA occurs as mineral structures external to the fibrils. The remainder is found constrained to the gap zones. Comparative studies of other species suggest that this structural motif is ubiquitous in all vertebrates

ALADIN is Required for the Production of Fertile Mouse Oocytes

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

The present study examined the ability of human monocytes to produce reactive oxygen intermediates after a contact with tumour cells. Monocytes generated oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide anion production, after stimulation with the tumour, but not with untransformed, cells. The use of specific oxygen radical scavengers and inhibitors, superoxide dismutase, catalase, dimethyl sulphoxide and deferoxamine as well as the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide, indicated that chemiluminescence was dependent on the production of superoxide anion and hydroxyl radical and the presence of myeloperoxidase. The tumour cell-induced chemiluminescent response of monocytes showed different kinetics from that seen after activation of monocytes with phorbol ester. These results indicate that human monocytes can be directly stimulated by tumour cells for reactive oxygen intermediate production. Spontaneous monocyte-mediated cytotoxicity towards cancer cells was inhibited by superoxide dismutase, catalase, deferoxamine and hydrazide, implicating the role of superoxide anion, hydrogen peroxide, hydroxyl radical and hypohalite. We wish to suggest that so-called ‘spontaneous’ tumoricidal capacity of freshly isolated human monocytes may in fact be an inducible event associated with generation of reactive oxygen intermediates and perhaps other toxic mediators, resulting from a contact of monocytes with tumour cells. © 1999 Cancer Research Campaig

Production of Single W Bosons at LEP

We report on the observation of single W boson production in a data sample collected by the L3 detector at LEP2. The signal consists of large missing energy final states with a single energetic lepton or two hadronic jets. The cross-section is measured to be $0.61^{+0.43}_{-0.33} \pm 0.05 \; \rm{pb}$ at the centre of mass energy \sqrt{s}=172 \GeV{}, consistent with the Standard Model expectation. From this measurement the following limits on the anomalous $\gamma$WW gauge couplings are derived at 95\% CL: $\rm -3.6 \Delta \kappa_\gamma 1.5$ and $\rm -3.6 \lambda_\gamma 3.6$

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Search for R-Parity Breaking Sneutrino Exchange at LEP

We report on a search for R--parity breaking effects due to supersymmetric tau--sneutrino exchange in the reactions e+e- to e+e- and e+e- to mu+mu- at centre--of--mass energies from 91~{\GeV} to 172~{\GeV}, using the L3 detector at LEP. No evidence for deviations from the Standard Model expectations of the measured cross sections and forward--backward asymmetries for these reactions is found. Upper limits for the couplings $\lambda_{131}$ and $\lambda_{232}$ for sneutrino masses up to m_{\SNT} \leq 190~\GeV are determined from an analysis of the expected effects due to tau sneutrino exchange

Measurement of the Average Lifetime of b-Hadrons in Z Decays

We present a measurement of the average b-hadron lifetime ${\rm \tau_b}$ at the $\mathrm{e^+e^-} \,$ collider LEP. Using hadronic Z decays collected in the period from 1991 to 1994, two independent analyses have been performed. In the first one, the b-decay position is reconstructed as a secondary vertex of hadronic b-decay particles. The second analysis is an updated measurement of ${\rm \tau_b}$ using the impact parameter of leptons with high momentum and high transverse momentum. The combined result is \begin{center} ${\rm \tau_b= [ 1549 \pm 9 \, (stat) \, \pm 15 \, (syst) ] \; fs \,}$ . \end{center} In addition, we measure the average charged b-decay multiplicity ${\rm \langle n_{\rm b}} \rangle$ and the normalized average b-energy ${\rm \langle x_E \rangle_{\rm b}}$ at LEP to be \begin{center} ${\rm \langle n_{\rm b} \rangle = 4.90 \pm 0.04 \ (stat) \pm 0.11 \, (syst)}$ , \end{center} \begin{center} ${\rm \langle x_E \rangle_{\rm b} = 0.709 \pm 0.004 \, (stat + syst).}$ \end{center

Search for new physics phenomena in fermion-pair production at LEP

The measurements of hadron and lepton--pair production cross sections and lepton--pair forward--backward asymmetries performed with the L3 detector at centre--of--mass energies between 130 GeV and 172 GeV are used to search for new physics phenomena. New physics effects involving four fermion vertices -- contact interactions -- are looked for in all channels. For hadron production the exchange of virtual leptoquarks and scalar quarks is studied. No evidence for deviations from the Standard Model expectations is found. Lower limits on the scale $\Lambda$ of contact interactions in the range 1.2 -- 7.1 TeV are obtained at the 95\% confidence level for various models. Upper limits on the coupling strengths of leptoquarks and scalar quarks are derived