Early growth response gene-2 (Egr-2) regulates the development of B and T cells

The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These include targeting the level of estrogen, blocking estrogen action at the ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is limited by either intrinsic or acquired resistance. Identifying the factors and pathways responsible for sensitivity and resistance remains a challenge in improving the treatment of breast cancer. With a better understanding of coordinated action of ER, its coregulatory factors, and the influence of other intracellular signaling cascades, improvements in breast cancer therapy are emerging

Yrast isomers in tin nuclei from heavy ion collisions and the νh_{11/2} subshell filling

none13Long-lived 10+ isomers in 122Sn and 124Sn have been identified among the products of 124Sn+325 MeV 76Ge collisions. The measurements virtually complete a series of B(E2) determinations for (νh11/2)n states in 116-130Sn, which pinpoint half filling of the νh11/2 subshell very close to N=73. Results for these Z=50 isotopes and for the N=82 isotones are contrasted, and an enlightening comparison between the effective E2 charges observec in tin and lead isotopes is developed.noneR. Broda;R. Mayer;I. Bearden;Ph. Benet;P. Daly;Z. Grabowski;M. Carpenter;R. Janssens;T. Khoo;T. Lauritsen;E. Moore;S. Lunardi;J. BlomqvistR., Broda; R., Mayer; I., Bearden; Benet, P. h.; P., Daly; Z., Grabowski; M., Carpenter; R., Janssens; T., Khoo; T., Lauritsen; E., Moore; Lunardi, Santo; J., Blomqvis

Feeding and decay of superdeformed states

The mechanisms for feeding and decay of superdeformed (SD) bands are examined. Data connected with both processes in {sup 192}Hg are compared with model calculations. The calculations successfully reproduce the data, suggesting that the mechanisms for both processes are understood. Constraints on the energy of the SD band energies and on the well-depths at low and high spins have been obtained. At the point of decay around spin 10, we suggest that the SD band is 3.3--4.3 MeV above the normal yrast line and that the well depths at spin 10 and 40 are 0.5--1.3 and 3.5--4.5 MeV, respectively

Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register

The objective of this study is to assess (1) the concordance and validity of schizophrenia register diagnoses among children and adolescents (early onset schizophrenia = EOS) in the Danish Psychiatric Central Research Register (DPCRR), and (2) the validity of clinical record schizophrenia diagnoses. Psychiatric records from 200 patients with a first-time diagnosis of schizophrenia (F20.x) at age  0.78–0.83 depending on classification. Compared to diagnoses made in outpatient settings, EOS diagnoses during hospitalizations were more likely to be valid and had fewer registration errors. Diagnosed in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge, it is possible to reduce the number of false-positives in register-based research of EOS

α decay of the neutron-deficient isotope At190

The α decay of the neutron-deficient At190 isotope was observed following the Rh103(Zr90,3n)At190 reaction at Argonne National Laboratory. The reaction products were separated from the beam using the Argonne Gas-Filled Analyzer and implanted into a double-sided Si strip detector. The spatial and temporal correlations between implanted nuclei and subsequent α decays towards the known daughter isotope Bi186 were used to identify and characterize At190 nuclei. Two possible decay scenarios are proposed for the At190→Bi186 decay