Sound can improve visual search in developmental dyslexia

We examined whether developmental dyslexic adults suffer from sluggish attentional shifting (SAS; Hari and Renvall in Trends Cogn Sci 5:525–532, 2001) by measuring their shifting of attention in a visual search task with dynamic cluttered displays (Van der Burg et al. in J Exp Psychol Human 34:1053–1065, 2008). Dyslexics were generally slower than normal readers in searching a horizontal or vertical target among oblique distracters. However, the addition of a click sound presented in synchrony with a color change of the target drastically improved their performance up to the level of the normal readers. These results are in line with the idea that developmental dyslexics have specific problems in disengaging attention from the current fixation, and that the phasic alerting by a sound can compensate for this deficit

Factors underlying the perturbation resistance of the trunk in the first part of a lifting movement

In the first part of lifting movements, the trunk movement is surprisingly resistant to perturbations. This study examined which factors contribute to this perturbation resistance of the trunk during lifting. Three possible mechanisms were studied: force-length-velocity characteristics of muscles, the momentum of the trunk as well as the effect of passive extending of the elbows. A forward dynamics modelling and simulation approach was adopted with two different input signals: (1) stimulation of Hill-type muscles versus (2) net joint moments. Experimental data collected during an unperturbed lifting movement were used as a reference, which a simulated lifting movement had to resemble. Subsequently, the simulated lifting movement was perturbed by applying 10 kg extra mass at the wrist (both before and after lift-off and with/without a fixed elbow), without modifying the input signals. The momentum of the trunk appeared to be insufficient to explain the perturbation resistance of trunk movements as found experimentally. In addition to the momentum of the trunk, the force-length-velocity characteristics of the muscles are necessary to account for the observed perturbation resistance. Initial extension of the elbow due to the mass perturbation delayed the propagation of the load to the shoulder. However, this delay is reduced due to the impedance at the elbow provided by the characteristics of muscles spanning the elbow. So, the force-length-velocity characteristics of the muscles spanning the elbow joint increase the perturbation at the trunk. © Springer-Verlag 2005

Induction of viral and tumour specific CTL responses using antibody targeted HLA class I peptide complexes

The production of cytotoxic T cells with specificity for cancer cells is a rapidly evolving branch of cancer therapeutics. A variety of approaches aim to amplify anti-tumour cytotoxic T cell responses using purified peptides, tumour cell lysates or recombinant HLA/peptide complexes in differing antigen presenting systems. Using a two-step biotin-streptavidin antibody targeting system, recombinant HLA-class I/peptide complexes were attached to the surface of B cells via the anti-CD20 B9E9-scFvSA antibody-streptavidin fusion protein. Flow cytometry with a conformation dependant monoclonal antibody to HLA class I indicated that targeted HLA-class I/peptide complexes remain on the surface of B cells in culture for periods in excess of 72 h. PBMCs were stimulated in vitro for 8–14 days using the autologous B cells as antigen presenting cells. Following a single cycle of stimulation specific cytotoxic T cell responses to targeted HLA-A2 complexes containing the M1, BMLF1 and Melan A peptides could be demonstrated by tetramer staining and Cr release assays. With the HLA-A2/BMLF1 complex up to 2.99% of CD8+ve cells were tetramer positive producing 20% lysis (E : T 10 : 1) of CIR-A2 target cells in an in vitro cytotoxicity assay compared to baseline levels of 0.09% tetramer +ve and 2% lysis in the unstimulated population. PBMCs from a healthy donor treated with two cycles of stimulations with targeted HLA-A2/Melan A complexes, demonstrated expansion of the melanA tetramer +ve population from 0.03% to 1.4% producing 15% lysis of Melan A pulsed target cells. With further consideration to the key variables of HLA/peptide complex density, the ratio of stimulator to effector cells and optimum cytokine support, this system should offer an easy and effective method for the in vitro amplification of specific cytotoxic T cell responses and warrants development for the in vivo induction of cytotoxic T cell responses in cancer therapy

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets: Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Contains fulltext : 52315.pdf (publisher's version ) (Closed access)Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined

Real-Time Quantitative (RQ-)PCR Approach to Quantify the Contribution of Proliferation to B Lymphocyte Homeostasis

The cells of the adaptive immune system, B and T lymphocytes, each generate a unique antigen receptor through V(D)J recombination of their immunoglobulin (Ig) and T-cell receptor (TCR) loci, respectively. Such rearrangements join coding elements to form a coding joint and delete the intervening DNA as circular excision products containing the signal joint. These excision circles are relatively stable structures that cannot replicate and have no function in the cell. Since the coding joint in the genome is replicated with each cell division, the ratio between coding joints and signal joints in a population of B cells can be used as a measure for proliferation. This chapter describes a real-time quantitative polymerase chain reaction (RQ-PCR)-based approach to quantify proliferation through calculating the ratio between coding joints and signal joints of the frequently occurring kappa-deleting rearrangements in the IGK light chain loci in man and mouse. The approach is useful to study the contribution of proliferation to B-cell homeostasis in health and disease.</p