Regulation of Signal Transducer and Activator of Transcription Signaling by the Tyrosine Phosphatase PTP-BL

SummarySignal Transducer and Activator of Transcription (STAT) proteins are a family of latent cytoplasmic transcription factors that are activated by tyrosine phosphorylation after cytokine stimulation. One mechanism by which STAT signaling is regulated is by dephosphorylation through the action of protein tyrosine phosphatases (PTP). We have identified PTP-Basophil like (PTP-BL) as a STAT PTP. PTP-BL dephosphorylates STAT proteins in vitro and in vivo, resulting in attenuation of STAT-mediated gene activation. In CD4+ T cells, PTP-BL deficiency leads to increased and prolonged activation of STAT4 and STAT6, and consequently enhanced T helper 1 (Th1) and Th2 cell differentiation. Taken together, our findings demonstrate that PTP-BL is a physiologically important negative regulator of the STAT signaling pathway

Sex Determination in the Social Amoeba <em>Dictyostelium discoideum</em>

The genetics of sex determination remains mysterious in many organisms including some that are otherwise well-studied. Here we report the discovery and analysis of the mating-type locus of the model organism Dictyostelium discoideum. Three forms of a single genetic locus specifies this species’ three mating-types: two versions of the locus are entirely different in sequence, and the third resembles a composite of the other two. Single, unrelated genes are sufficient to determine two of the mating-types, while homologues of both these genes are required in the composite type. The key genes encode polypeptides that possess no recognisable similarity to established protein families. Sex determination in the social amoebae thus appears to use regulators unrelated to any currently known

Adubação NK no desenvolvimento e na concentração de macronutrientes no florescimento do feijoeiro

Nitrogen and potassium are absorbed and transported more than any other element by bean plants. Fertilizer levels vary greatly among agriculturists and, therefor our aim was to study the effect of N levels (0, 60, 80, 100, 120 kg ha-1) and K2O levels (0, 60, 120 kg ha-1) on bean development, evaluating number of flowers, fresh weight, dry weight and macronutrients during flowering. The experiment was carried out at Botucatu, SP, Brazil, in plastic tunnels, with the bean cultivar Pérola. Two plants were grown for 50 days in 15L pots filled with an Haplorthox. The NK fertilizations were parceled 20 and 40 days after sowing. The parameters were influenced by N and K interactions. Soil N fertilization increases dry weight production without interfering on bean shoot N, K, Ca and Mg levels. Nitrogen omission reduces leaf chlorophyll content, decreasing dry weight, having no influence on flower number. K levels had no influence on plant Ca and Mg levels.O nitrogênio e o potássio são os elementos mais absorvidos e exportados pelo feijoeiro, sendo a adubação mineral entre os produtores bastante variável quanto as doses aplicadas. Este trabalho avalia os efeitos de doses de N (0, 60, 80, 100 e 120 kg ha-1) e K2O (0, 60 e 120 kg ha-1) no desenvolvimento do feijoeiro, por meio do número de unidades estruturais, peso de material fresco e seco, e a concentração de macronutrientes no florescimento. O experimento foi realizado em Botucatu, SP., em túnel plástico, utilizando-se a cultivar 'Pérola'. Duas plantas foram cultivadas em vasos de 15 L, preenchidos com terra de Latossolo Vermelho Distrófico típico, textura média, por 50 dias. As doses de NK foram parceladas em cobertura aos 20 e 40 dias após semeadura. As variáveis estudadas foram influenciadas pela interação entre as doses de N e K. A adubação parcelada com N via solo, independentemente das doses utilizadas ou da fertilização com K, aumenta a produção de matéria seca sem interferir nos teores de N da parte aérea do feijoeiro, assim como os de K, Ca e Mg. A omissão de N em cobertura reduz o teor de clorofila, diminuindo a produção de matéria seca, mas não interferindo no número de flores. Os níveis de K utilizados não diminuíram os teores de Ca e Mg da planta

Radiographer involvement in mammography image interpretation: a survey of United Kingdom practice

Breast cancer is most often diagnosed using x-ray mammography. Traditionally mammography images have been interpreted and reported by medically qualified practitioners - radiologists. Due to radiologist workforce shortages in recent years some nonmedical practitioners, radiographers, now interpret and report mammography images. The aims of this survey were to describe the characteristics and practices of radiographers who interpret and report mammography images in NHS hospitals in the UK, and in particular to establish the extent of their practice beyond low-risk asymptomatic screening cases. This service evaluation demonstrated that UK radiographers are interpreting and reporting images across the full spectrum of clinical indications for mammography including: low-risk population screening, symptomatic, annual surveillance, family history and biopsy / surgical cases. The survey revealed that radiographers are involved in a diverse range of single and double reading practices where responsibility for diagnostic decision making is shared or transferred between radiologists and / or other radiographers. Comparative analysis of subgroup data suggested that there might be differences in the characteristics and practices of radiographers who interpret only low-risk screening mammograms and those who interpret and report a wider range of cases. The findings of this survey provide a platform for further research to investigate how and why the roles and responsibilities of radiographers who interpret and report mammograms vary between organisations, between practitioners and across different examinations. Further research is also needed to explore the implications of variation in practice for patients, practitioners and service providers

Dynamic action of the Sec machinery during initiation, protein translocation and termination

Protein translocation across cell membranes is a ubiquitous process required for protein secretion and membrane protein insertion. In bacteria, this is mostly mediated by the conserved SecYEG complex, driven through rounds of ATP hydrolysis by the cytoplasmic SecA, and the trans-membrane proton motive force. We have used single molecule techniques to explore SecY pore dynamics on multiple timescales in order to dissect the complex reaction pathway. The results show that SecA, both the signal sequence and mature components of the pre-protein, and ATP hydrolysis each have important and specific roles in channel unlocking, opening and priming for transport. After channel opening, translocation proceeds in two phases: a slow phase independent of substrate length, and a length-dependent transport phase with an intrinsic translocation rate of ~40 amino acids per second for the proOmpA substrate. Broad translocation rate distributions reflect the stochastic nature of polypeptide transport

Isolation of a small molecule inhibitor of DNA base excision repair

The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3′-phosphodiesterase and 3′-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy

ARTIFICIAL INTELLIGENCEMARKUPLANGUAGE: A BRIEF TUTORIAL

ABSTRACT The purpose of this paper is to serve as a reference guide for the development ofchatterbots implemented with the AIML language. In order to achieve this, the main concepts in Pattern Recognition area are described because the AIML uses such theoretical framework in their syntactic and semantic structures. After that, AIML language is described and each AIML command/tag is followed by an application example. Also, the usage of AIML embedded tags for the handling of sequence dialogue limitations between humans and machinesis shown.Finally, computer systems that assist in the design ofchatterbots with the AIML language are classified and described

The clinical utility of hybrid imaging for the identification of vulnerable plaque and vulnerable patients

Despite decades of research and major innovations in technology, cardiovascular disease remains the leading cause of death globally. Our understanding of major cardiovascular events and their prevention is centred around the atherosclerotic plaque and the processes that ultimately lead to acute plaque rupture. Recent advances in hybrid imaging technology allow the combination of high spatial resolution and anatomical detail with molecular assessments of disease activity. This provides the ability to identify vulnerable plaque characteristics and differentiate active and quiescent disease, with the potential to improve patient risk stratification. Combined positron emission tomography and computed tomography is the prototypical non-invasive hybrid imaging technique for coronary artery plaque assessment. In this review we discuss the current state of play in the field of hybrid coronary atherosclerosis imaging

Rubinstein-Taybi syndrome with scoliosis

<p>Abstract</p> <p>Study Design</p> <p>Case report.</p> <p>Objective</p> <p>The authors present the case of a 14-year-old boy with Rubinstein-Taybi syndrome (RSTS) presenting scoliosis.</p> <p>Summary of Background Data</p> <p>There have been no reports on surgery for RSTS presenting scoliosis.</p> <p>Methods</p> <p>The patient was referred to our hospital for evaluation of a progressive spinal curvature. A standing anteroposterior spine radiograph at presentation to our hospital revealed an 84-degree right thoracic curve from T6 to T12, along with a 63-degree left lumbar compensatory curve from T12 to L4. We planned a two-staged surgery and decided to fuse from T4 to L4. The first operation was front-back surgery because of the rigidity of the right thoracic curve. The second operation of lumbar anterior discectomy and fusion was arranged 9 months after the first surgery to prevent the crankshaft phenomenon due to his natural course of adolescent growth. To avoid respiratory complications, the patient was put on a respirator in the ICU for several days after both surgeries.</p> <p>Results</p> <p>Full-length spine radiographs after the first surgery revealed no instrumentation failure and showed that the right thoracic curve was corrected to 31 degrees and the left lumbar curve was corrected to 34 degrees. No postoperative complications occurred after both surgeries.</p> <p>Conclusions</p> <p>We succeeded in treating the patient without complications. Full-length spine standing radiographs at one year after the second operation demonstrated a stable bony arthrodesis with no loss of initial correction.</p

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa