Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes

Properties of Factorial Cumulant to Factorial Moment Ratio

It is shown that the ratio of factorial cumulant moments to factorial moments for a multiplicity distribution truncated in the tail reveals oscillations in sign similar to those observed in experimental data. It is suggested that this effect be taken into account in the analysis of data in order to obtain correct physical information on the multiplicity distributions.Comment: (LaTeX + epsfig, 8 pages including 3 PostScript figures, all encoded via uufiles), DFTT 46/9

Quantification of retinal pigment epithelial phenotypic variation using laser scanning cytometry

PurposeQuantifying phenotypic variation at the level of protein expression (variegation) within populations of retinal pigment epithelium (RPE) cells may be important in the study of pathologies associated with this variation. The lack of quantitative methods for examining single cells, however, and the variable presence of pigment and/or lipofuscin complicate this experimental goal. We have applied the technique of laser scanning cytometry (LSC) to paraffin sections of mouse and human eyes to evaluate the utility of LSC for these measurements.MethodsMouse eyes were perfusion fixed in 4% paraformaldehyde and embedded in paraffin. Postmortem human eyes were fixed and dissected to obtain a 9-mm punch, which was then embedded in paraffin. A laser scanning cytometer equipped with violet, argon, and helium-neon lasers and the detectors for blue, green, and long red were used to record the fluorescence of each individual cell at all three wavelengths. Raw data were recorded and processed using the WinCyte software. Individual nuclei were identified by the fluorescence of the 4',6-diamidino-2-phenylindole (DAPI) nuclear counterstain. Next, RPE cells were uniquely identified in the green channel using an anti-retinal pigment epithelium-specific protein 65 kDa (anti-RPE65) monoclonal antibody with an Alexa Fluor 488-labeled secondary antibody. Mn-superoxide dismutase (MnSOD) was quantified in the long-red channel using an anti-MnSOD antibody and an Alexa Fluor 647-labeled secondary antibody. MnSOD(+) and RPE65(+) cells exhibited peaks in the plot of fluorescence intensity versus cell number, which could be characterized by the mean fluorescence intensity (MFI), the coefficient of variation (CV), and the percentage of total RPE cells that were also labeled for MnSOD.ResultsRPE cells can be uniquely identified in human and mouse paraffin sections by immunolabeling with anti-RPE65 antibody. A second antigen, such as MnSOD, can then be probed only within this set of RPE. Results are plotted primarily with the population frequency diagram, which can be subdivided into multiple regions. The data collected for each region include the MFI, the CV, and the number of cells that are immunolabeled in that region. Background interference from pigment or autofluorescent material can be successfully overcome by elevating the concentrations of fluorescent secondary antibodies. In the human and mouse eyes, age-related changes in MFI, CV, and percent RPE cells immunolabeled for MnSOD were observed.ConclusionsThe extent of the variability of gene expression in RPE cells at the protein level can be quantified by LSC. Relative changes in the MFI, the CV, and/or percentage of RPE cells double labeled for a second antigen quantify the changes observed. The analysis of these data also suggest whether the effects observed are related to local changes in transcription (alterations of CV) or major changes of protein expression (MFI), which are likely to be due to changes in the chromatin structure. The changes of these variables with age suggest that the observed age-related variegation is primarily due to changes in the chromatin structure in individual cells

Superconformal constraints for QCD conformal anomalies

Anomalous superconformal Ward identities and commutator algebra in N = 1 super-Yang-Mills theory give rise to constraints between the QCD special conformal anomalies of conformal composite operators. We evaluate the superconformal anomalies that appear in the product of renormalized conformal operators and the trace anomaly in the supersymmetric spinor current and check the constraints at one-loop order. In this way we prove the universality of QCD conformal anomalies, which define the non-diagonal part of the anomalous dimension matrix responsible for scaling violations of exclusive QCD amplitudes at the next-to-leading order.Comment: 30 pages, 2 figures, LaTe

Strategies for the analysis of osteitic bone defects at the diaphysis of long bones

Septic diseases of the bone and the immediate surrounding soft tissue, i.e., osteitis, belong to the most alarming findings in recent traumatology and orthopedic surgery. The paramount goal of this therapy is to preserve the stable weight-bearing bones while maintaining a correct axis and proper working muscles and joints, in order to avoid permanent disability in the patient. “State-of-the-art” therapy of osteitis/osteomyelitis therapy has two priorities: eradication of the infection and reconstruction of bone and soft tissue. Surgical treatment of the affected bone segments and soft tissue, followed by reconstructive methods, continues to be the main basic therapy. It is often extremely difficult to decide whether the affected bone segment has to be resected, or whether bone continuity can be preserved. The following paper provides strategies and guidance to help guide decisions in this complex and challenging area

An SU(3) model for octet baryon and meson fragmentation

The production of the octet of baryons and mesons in e^+ e^- collisions is analysed, based on considerations of SU(3) symmetry and a simple model for SU(3) symmetry breaking in fragmentation functions. All fragmentation functions, D_q^h(x, Q^2), describing the fragmentation of quarks into a member of the baryon octet (and similarly for fragmentation into members of the meson octet) are expressed in terms of three SU(3) symmetric functions, \alpha(x, Q^2), \beta(x, Q^2), and \gamma(x, Q^2). With the introduction of an SU(3) breaking parameter, \lambda, the model is successful in describing hadroproduction data at the Z pole. The fragmentation functions are then evolved using leading order evolution equations and good fits to currently available data at 34 GeV and at 161 GeV are obtained.Comment: 24 pages LaTeX file including 11 postscript figure file

Multiplicity distributions inside parton cascades developing in a medium

The explanation of the suppression of high-pT hadron yields at RHIC in terms of jet-quenching implies that the multiplicity distributions of particles inside a jet and jet-like particle correlations differ strongly in nucleus-nucleus collisions at RHIC or at the LHC from those observed at e+e- or hadron colliders. We present a framework for describing the medium-induced modification, which has a direct interpretation in terms of a probabilistic medium-modified parton cascade, and which treats leading and subleading partons on an equal footing. We show that our approach can account for the strong suppression of single inclusive hadron spectra measured in Au-Au collisions at RHIC, and that this implies a characteristic distortion of the single inclusive distribution of soft partons inside the jet. We determine, as a function of the jet energy, to what extent the soft fragments within a jet can be measured above some momentum cut.Comment: 5 pages, 4 eps-figures; talk given at Hot Quarks 2006, Villasimius (Sardinia, Italy), May 15-20, 200

Clan structure analysis and new physics signals in pp collisions at LHC

The study of possible new physics signals in global event properties in pp collisions in full phase space and in rapidity intervals accessible at LHC is presented. The main characteristic is the presence of an elbow structure in final charged particle MD's in addition to the shoulder observed at lower c.m. energies.Comment: 9 pages, talk given at Focus on Multiplicity (Bari, Italy, June 2004

MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients