Attention, memory and verbal learning and their relation to schizotypal traits in unaffected parents of schizophrenic patients

The main objective of this ex post facto study is to compare the differencesin cognitive functions and their relation to schizotypal personality traits between agroup of unaffected parents of schizophrenic patients and a control group. A total of 52unaffected biological parents of schizophrenic patients and 52 unaffected parents ofunaffected subjects were assessed in measures of attention (Continuous PerformanceTest- Identical Pairs Version, CPT-IP), memory and verbal learning (California VerbalLearning Test, CVLT) as well as schizotypal personality traits (Oxford-Liverpool Inventoryof Feelings and Experiences, O-LIFE). The parents of the patients with schizophreniadiffer from the parents of the control group in omission errors on the ContinuousPerformance Test- Identical Pairs, on a measure of recall and on two contrast measuresof the California Verbal Learning Test. The associations between neuropsychologicalvariables and schizotpyal traits are of a low magnitude. There is no defined pattern ofthe relationship between cognitive measures and schizotypal traits

Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory.

Immune protection from intracellular pathogens depends on the generation of terminally differentiated effector and of multipotent memory precursor CD8 T cells, which rapidly regenerate effector and memory cells during recurrent infection. The identification of factors and pathways involved in CD8 T cell differentiation is of obvious importance to improve vaccination strategies. Here, we show that mice lacking T cell factor 1 (Tcf-1), a nuclear effector of the canonical Wingless/Integration 1 (Wnt) signaling pathway, mount normal effector and effector memory CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV). However, Tcf-1-deficient CD8 T cells are selectively impaired in their ability to expand upon secondary challenge and to protect from recurrent virus infection. Tcf-1-deficient mice essentially lack CD8 memory precursor T cells, which is evident already at the peak of the primary response, suggesting that Tcf-1 programs CD8 memory cell fate. The function of Tcf-1 to establish CD8 T cell memory is dependent on the catenin-binding domain in Tcf-1 and requires the Tcf-1 coactivators and Wnt signaling intermediates beta-catenin and gamma-catenin. These findings demonstrate that the canonical Wnt signaling pathway plays an essential role for CD8 central memory T cell differentiation under physiological conditions in vivo. They raise the possibility that modulation of Wnt signaling may be exploited to improve the generation of CD8 memory T cells during vaccination or for therapies designed to promote sustained cytotoxic CD8 T cell responses against tumors.

On the origin and scope of the second language speech production disadvatage

Los hablantes bilingües tienen un acceso al léxico más lento y menos robusto que los monolingües, incluso cuando hablan en su lengua materna y dominante. Este fenómeno, comúnmente llamado “la desventaja bilingüe” también se observa en hablantes de una segunda lengua en comparación con hablantes de una primera lengua. Una causa que posiblemente contribuya a estas desventajas es el uso de control inhibitorio durante la producción del lenguaje: la inhibición de palabras coactivadas de la lengua actualmente no en uso puede prevenir intrusiones de dicha lengua, pero al mismo tiempo ralentizar la producción del lenguaje. El primer objetivo de los estudios descritos en este informe era testear esta hipótesis mediante diferentes predicciones generadas por teorías de control inhibitorio del lenguaje. Un segundo objetivo era investigar la extensión de la desventaja bilingüe dentro y fuera de la producción de palabras aisladas, así como avanzar en el conocimiento de las variables que la modulan. En lo atingente al primer objetivo, la evidencia obtenida es incompatible con un control inhibitorio global, desafiando la idea de mecanismos específicos en el hablante bilingüe utilizados para la selección léxica. Esto implica que una explicación común para el control de lenguaje y la desventaja bilingüe en el acceso al léxico es poco plausible. En cuanto al segundo objetivo, los resultados muestran que (a) la desventaja bilingüe no tiene un impacto al acceso a la memoria; (b) la desventaja bilingüe extiende a la producción del habla conectada; y (c) similitudes entre lenguas a diferentes niveles de representación así como la frecuencia de uso son factores que modulan la desventaja bilingüe.   

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

Simultaneous co-expression of memory- and effector-related genes by individual human CD8 T cells depends on antigen specificity and differentiation

Purpose/Objective: Phenotypic and functional T cell properties are usually analyzed at the level of defined cell populations. However, large differences between individual T cells may have important functional consequences. To answer this issue, we performed highly sensitive single-cell gene expression profiling, which allows the direct ex vivo characterization of individual virus- and tumor-specific T cells from healthy donors and melanoma patients. Materials and methods: HLA-A*0201-positive patients with stage III/ IV metastatic melanoma were included in a phase I clinical trial (LUD- 00-018). Patients received monthly low-dose of the Melan-AMART- 1 26_35 unmodified natural (EAAGIGILTV) or the analog A27L (ELAGIGILTV) peptides, mixed CPG and IFA. Individual effector memory CD28+ (EM28+) and EM28- tetramer-specific CD8pos T cells were sorted by flow cytometer. Following direct cell lysis and reverse transcription, the resulting cDNA was precipitated and globally amplified. Semi-quantitative PCR was used for gene expression and TCR BV repertoire analyses. Results: We have previously shown that vaccination with the natural Melan-A peptide induced T cells with superior effector functions as compared to the analog peptide optimized for enhanced HLA binding. Here we found that natural peptide vaccination induced EM28+ T cells with frequent co-expression of both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3 and CCR5) and effector-related genes (IFNG, KLRD1, PRF1 and GZMB), comparable to protective EBV- and CMV-specific T cells. In contrast, memory/homing- and effectorassociated genes were less frequently co-expressed after vaccination with the analog peptide. Conclusions: These findings reveal a previously unknown level of gene expression diversity among vaccine- and virus-specific T cells with the simultaneous co-expression of multiple memory/homing- and effector- related genes by the same cell. Such broad functional gene expression signatures within antigen-specific T cells may be critical for mounting efficient responses to pathogens or tumors. In summary, direct ex vivo high-resolution molecular characterization of individual T cells provides key insights into the processes shaping the functional properties of tumor- and virus-specific T cells.

On the significance of CD8 alpha alpha expression for T cell memory.

Longitudinal studies on the kinetics of viral antigen specific CD8 T cell responses have led to a model whereby a relatively small subset of the primary effector CD8 T cells expanding after the first week of acute viral infection initiate a program of cell survival and differentiation into long lived memory T cells. These T cells are then critical for maintaining protective immunity to subsequent viral infection. Recent observations, using fluorescent tetramers of the MHC class Ib molecule TL, link transient expression of CD8alphaalpha homodimers on expanding primary effector CD8 T cells to the generation of memory cells. At present it is controversial what the role of CD8alphaalpha is in the generation of memory CD8 T cells. The involvement of the high affinity CD8alphaalpha ligand, the TL molecule, is not understood either. However, evidence from two viral infection models in mice, including one paper in this issue of the European Journal of Immunology, suggest a role for CD8alphaalpha in this process and call for additional research focus into these issues.

Using qualia information to identify lexical semantic classes in an unsupervised clustering task

Acquiring lexical information is a complex problem, typically approached by relying on a number of contexts to contribute information for classification. One of the first issues to address in this domain is the determination of such contexts. The work presented here proposes the use of automatically obtained FORMAL role descriptors as features used to draw nouns from the same lexical semantic class together in an unsupervised clustering task. We have dealt with three lexical semantic classes (HUMAN, LOCATION and EVENT) in English. The results obtained show that it is possible to discriminate between elements from different lexical semantic classes using only FORMAL role information, hence validating our initial hypothesis. Also, iterating our method accurately accounts for fine-grained distinctions within lexical classes, namely distinctions involving ambiguous expressions. Moreover, a filtering and bootstrapping strategy employed in extracting FORMAL role descriptors proved to minimize effects of sparse data and noise in our task.

Towards the Fully Automatic Merging of Lexical Resources: A Step Forward

This article reports on the results of the research done towards the fully automatically merging of lexical resources. Our main goal is to show the generality of the proposed approach, which have been previously applied to merge Spanish Subcategorization Frames lexica. In this work we extend and apply the same technique to perform the merging of morphosyntactic lexica encoded in LMF. The experiments showed that the technique is general enough to obtain good results in these two different tasks which is an important step towards performing the merging of lexical resources fully automatically.

Automatic Lexical Semantic Classification of Nouns

The work we present here addresses cue-based noun classification in English and Spanish. Its main objective is to automatically acquire lexical semantic information by classifying nouns into previously known noun lexical classes. This is achieved by using particular aspects of linguistic contexts as cues that identify a specific lexical class. Here we concentrate on the task of identifying such cues and the theoretical background that allows for an assessment of the complexity of the task. The results show that, despite of the a-priori complexity of the task, cue-based classification is a useful tool in the automatic acquisition of lexical semantic classes.

Towards the Automatic Merging of Lexical Resources: Automatic Mapping

Lexical Resources are a critical component for Natural Language Processing applications. However, the high cost of comparing and merging different resources has been a bottleneck to have richer resources with a broad range of potential uses for a significant number of languages.With the objective of reducing cost byeliminating human intervention, we present a new method for automating the merging of resources,with special emphasis in what we call the mapping step. This mapping step, which converts the resources into a common format that allows latter the merging, is usually performed with huge manual effort and thus makes the whole process very costly. Thus, we propose a method to perform this mapping fully automatically. To test our method, we have addressed the merging of two verb subcategorization frame lexica for Spanish, The resultsachieved, that almost replicate human work, demonstrate the feasibility of the approach.

A Method Towards the Fully Automatic Merging of Lexical Resources

Lexical Resources are a critical component for Natural Language Processing applications. However, the high cost of comparing and merging different resources has been a bottleneck to obtain richer resources and a broader range of potential uses for a significant number of languages. With the objective of reducing cost by eliminating human intervention, we present a new method towards the automatic merging of resources. This method includes both, the automatic mapping of resources involved to a common format and merging them, once in this format. This paper presents how we have addressed the merging of two verb subcategorization frame lexica for Spanish, but our method will be extended to cover other types of Lexical Resources. The achieved results, that almost replicate human work, demonstrate the feasibility of the approach.

Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides

OBJECTIVE: A distinct subset of proinflammatory CD4+ T cells that produce interleukin-17 was recently identified. These cells are implicated in different autoimmune disease models, such as experimental autoimmune encephalomyelitis and collagen-induced arthritis, but their involvement in human autoimmune disease has not yet been clearly established. The purpose of this study was to assess the frequency and functional properties of Th17 cells in healthy donors and in patients with different autoimmune diseases. METHODS: Peripheral blood was obtained from 10 psoriatic arthritis (PsA), 10 ankylosing spondylitis (AS), 10 rheumatoid arthritis (RA), and 5 vitiligo patients, as well as from 25 healthy donors. Synovial tissue samples from a separate group of patients were also evaluated (obtained as paraffin-embedded sections). Peripheral blood cells were analyzed by multiparameter flow cytometry and immunohistochemistry. Cytokine production was examined by enzyme-linked immunosorbent assay and intracellular cytokine staining using specific monoclonal antibodies. Synovial tissue was examined for infiltrating T cells by immunohistochemical analysis. RESULTS: We found increased numbers of circulating Th17 cells in the peripheral blood of patients with seronegative spondylarthritides (PsA and AS), but not in patients with RA or vitiligo. In addition, Th17 cells from the spondylarthritis patients showed advanced differentiation and were polyfunctional in terms of T cell receptor-driven cytokine production. CONCLUSION: These observations suggest a role of Th17 cells in the pathogenesis of certain human autoimmune disorders, in particular the seronegative spondylarthritides.

Sex differences: From mental rotation to object location memory, an ERP study

Sex differences in cognition have been largely investigated. The most consistent sex differences favoring females are observed in object location memory involving the left hemisphere whereas the most consistent sex differences favoring males are observed in tasks that require mental rotation involving the right hemisphere. Here we used a task involving these two abilities to see the impact of mental rotation on object location memory. To that end we used a combination of behavioral and event-related potential (ERP) electroencephalography (EEG) measures.A computer screen displayed a square frame of 4 pairs of images (a "teddy" bear, a shoe, an umbrella and a lamp) randomly arranged around a central fixation cross. After a 10-second interval for memorization, images disappeared and were replaced by a test frame with no image but a random pair of two locations marked in black. In addition, this test frame was randomly displayed either in the original orientation (0° rotation) or in the rotated one (90° clockwise - CW - or 90° counterclockwise - CCW). Preceding the test frame, an arrow indicating the presence or the absence of rotation of the frame was displayed on the screen. The task of the participants (15 females and 15 males) was to determine if two marked locations corresponded or not to a pair of identical images. Each response was followed by feedback.Findings showed no significant sex differences in the performance of the original orientation. In comparison with this position, the rotation of the frame produced an equal decrease of male and female performance. In addition, this decrease was significantly higher when the rotation of the frame was in a CCW direction. We further assessed the ERP when the arrow indicated the direction of rotation as stimulus-onset, during four time windows representing major components C1, P1, N1 and N2. Although no sex differences were observed in performance, brain activities differed according to sex. Enhanced amplitudes were found for the CCW compared to CW rotation over the right posterior areas for the P1, N1 and N2 components for men as well as for women. Major topographical differences related to sex were measured for the CW rotation condition as marked lateralized amplitude: left-hemisphere amplitude larger than right one was measured during P1 time range for men. These similar patterns prolonged from P1 to N1 for women. Early distinctions were found in interaction with sex between CCW and CW waveform amplitudes, expressing over anterior electrode sites during C1 time range (0-50 ms post-stimulus).In conclusion (i) women do not outperform men in object location memory in this study (absence of rotation condition); (ii) mental rotation, in particular the direction of rotation, influences performance on object location memory; (iii) CCW rotation is associated with activity in the right parietal hemisphere whereas the CW rotation involves the left parietal hemisphere; (iv) this last effect is less pronounced in males, which could explain why greater involvement of right parietal areas in men and of bilateral posterior areas in women is generally reported in mental rotation tasks; and (v) the early distinctions between both directions of rotation located over anterior sites could be related to sex differences in their respective involvement of control mechanisms.

Allostatic working memory processing in schizophrenia: Human and animal model coherence

The most evident symptoms of schizophrenia are severe impairment of cognitive functions like attention, abstract reasoning and working memory. The latter has been defined as the ability to maintain and manipulate on-line a limited amount of information. Whereas several studies show that working memory processes are impaired in schizophrenia, the specificity of this deficit is still unclear. Results obtained with a new paradigm, involving visuospatial, dynamic and static working memory processing, suggest that schizophrenic patients rely on a specific compensatory strategy. An animal model of schizophrenia with a transient deficit in glutathione during the development reveals similar substitutive processing, masking the impairment in working memory functions in specific test conditions only. Taken together, these results show coherence between working memory deficits in schizophrenic patients and in animal models. More generally, it is possible to consider that the pathological state may be interpreted as a reduced homeostatic reserve. However, this may be balanced in specific situations by efficient allostatic strategies. Thus, the pathological condition would remain latent in several situations, due to such allostatic regulations. However, to maintain a performance based on highly specific strategies requires in turn specific conditions, limitating adaptative resources in humans and in animals. In summary, we suggest that the psychological and physical load to maintain this rigid allostatic state is very high in patients and animal subjects.