Inclusion of CpG adjuvant with plasmid DNA coding for NcGRA7 improves protection against congenital neosporosis

The present study showed that incorporation of CpG adjuvant into plasmid DNA coding for NcGRA7 antigen resulted in a twofold increase in the level of protection against congenital transfer of Neospora caninum. The level of protection was considerably higher than that observed in pups born from dams immunized with nonrecombinant plasmid.     

The immunoregulatory nature of iron. II. Lymphocyte surface marker expression

Previously, we presented preliminary evidence that supported our hypothesis for the immunoregulatory nature of iron [7]. The objective of the present work was to test that hypothesis in greater detail. Our approach was to examine the effect that iron had on the expression of the surface markers on lymphocytes that had been activated by pokeweed mitogen (PWM). The two categories of lymphoid surface molecules were enumerated on those cells; first were those that identify T lymphocytes and second, those that appear on the membrane of T cells following activation. The results, as regards T cell-associated molecules, demonstrated that iron suppresses the expression of the molecules identified by the monoclonal antibodies OKT3 and OKT4. It suppressed expression of the T4 molecule in PWM-activated cells (30.6% +/- 4.5; n = 5) compared with untreated but activated cells (52.2% +/- 2.9; n = 5; P = 1.9 X 10(-3) resulting in a reduced helper:suppressor T cell ratio from 2.2 +/- 0.4 to 1.2 +/- 0.3. With regard to activation-associated lymphocyte markers, iron significantly enhanced expression of the receptor for transferrin as identified by the monoclonal antibody, OKT9. However, it failed to change significantly the expression of three other activation-associated markers, namely, Ia, T10, and the receptor that forms thermostable erythrocyte-rosettes (TE-R) with sheep red blood cells (SRC). We conclude from those results that iron has a differential immunoregulatory influence on the expression of certain lymphocyte surface molecules on actively dividing lymphocytes.     

The myogenic response in isolated rat cerebrovascular arteries: vessel model

We develop an integrated model of isolated rat arterial resistance vessel (RV), which can simulate its major property of myogenic response. The vascular smooth muscle cell is an important component of the wall of this vessel, and serves as a vasomotor organ providing the active tension generation that underlies the myogenic response of the wall to stretch. In the previous study, we focused on the development of a smooth muscle cell model that can mimic the strain-sensing and force-generating features of the myogenic mechanism. In the current model, we embed this cell model in a larger vessel wall configuration, and couple the time course of cellular contractile activation to macroscopic changes in vessel diameter. The integrated model is used to mimic published pressure-vessel diameter data obtained from isolated RVs that are mounted in a hydraulic test apparatus. The model provides biophysically based insights into the myogenic mechanism as it responds to changes in transmural pressure, in the presence and absence of Ca2+ blockers applied to the bathing fluid.It mimics measured data very well and provides a model that is able to link events at subcellular level to macroscopic changes in vessel diameter. The model initiates a mechanistic approach to investigate myogenic response, which has not been taken previously by any other models.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

Production and characterization of monoclonal antibodies specific for the murine T cell receptor ζ chain

The T cell receptor (TCR) comprises an antigen-specific β heterodimer non-covalently associated with the CD3 γδε and TCR ζ subunits. Both the CD3 and TCR ζ subunits are proposed to be responsible for the intracellular signal-transduction events. We report here the production of eight monoclonal antibodies (mAbs) that bind in an ELISA assay to a 113 amino acid synthetic peptide corresponding to the cytoplasmic domain of TCR ζ. Western blot analysis of anti-CD8 precipitates of lysates of transfectants expressing chimeric CD8/ζ constructs encoding increasing COOH-terminal truncations of TCR ζ indicates that four of these mAbs recognized the region of TCR ζ chain comprising the last 29 COOH-terminal residues. Thus, this region of TCR ζ may encode an immunodominant epitope. Furthermore, one of these mAbs, G3, is capable of precipitating both non-phosphorylated and tyrosine phosphorylated TCR ζ. The G3 mAb should be useful for elucidiating the structural and signalling characteristics of the TCR ζ chain.     

Neuropsychological Deficit and Academic Performance in Children and Adolescents Following Traumatic Brain Injury

Evaluated the utility of neuropsychological testing in predictingacademic outcome in children 1 year following traumatic braininjury (TBI). Fifty-one schoolage children who were admittedto hospital after TBI were assessed with a battery of neuropsychologicalmeasures at 3 months postinjury. Academic achievement was assessedat 3 and 12 months postinjury. The neuropsychological batteryincluded intelligence testing and measures of memory, learning,and speed of information processing. Academic outcome was assessedin terms of post-TBI changes in reading, spelling, and arithmetic;changes in teacher ratings of school performance; and changein school placement. According to logistic regression analysis,change in placement from regular to special education at 1-yearpost-TBI was predicted by injury severity and by neuropsychologicalperformance at 3 months post-TBI. Findings suggest that neuropsychologicaltesting is useful in identifying children with special educationalneeds subsequent to TBI.     

The stability and chemical stress relaxation of peroxide cured polyurethane elastomers

The chemical stress relaxation of two polyurethane elastomers Genthane S and Adiprene CM has been studied in air and in nitrogen in the temperature range 60 to 150°C. Both continuous and intermittent stress relaxation measurements were made on well characterized samples covering a range of crosslink densities. Scission and crosslinking reactions were observed for both the polyester based Genthane S and the polyether based Adiprene CM. The degradation of Genthane S is largely non oxidative and the scission reaction involves the main chain. The behaviour of Adiprene CM under nitrogen broadly resembles that of Genthane S; it differs from Genthane S in that it also undergoes an oxidative reaction. Activation energies for the scission and crosslinking processes were evaluated from kinetic analysis. Pretreatment of the elastomers with isocyanates inhibits both of these reactions. A mechanism involving the urethane group is proposed to account for the degradation behaviour and the role of water in this respect is discussed briefly.