tbuckley/cabot-search huggingface dataset:
Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture
Authors: Stefan Grob, Marc W Schmid, Nathan W Luedtke, Thomas Wicker, Ueli Grossniklaus
Journal: Genome biology (2013)

The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization. Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes.
Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey Commentary: efficient research gives direction on prisoners' and the wider public health---except in England and Wales
Authors: J. Long, S. Allwright, J. Barry, S. R. Reynolds, L. Thornton, F. Bradley, J. V Parry, S. M Bird
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To determine the prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in entrants to Irish prisons and to examine risk factors for infection. <b>Design:</b> Cross sectional, anonymous survey, with self completed risk factor questionnaire and oral fluid specimen for antibody testing. <b>Setting:</b> Five of seven committal prisons in the Republic of Ireland. <b>Participants:</b> 607 of the 718 consecutive prison entrants from 6 April to 1 May 1999. <b>Main outcome measures:</b> Prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in prison entrants, and self reported risk factor status. <b>Results:</b> Prevalence of antibodies to hepatitis B core antigen was 37/596 (6%; 95% confidence interval 4% to 9%), to hepatitis C virus was 130/596 (22%; 19% to 25%), and to HIV was 12/596 (2%; 1% to 4%). A third of the respondents had never previously been in prison; these had the lowest prevalence of antibodies to hepatitis B core antigen (4/197, 2%), to hepatitis C (6/197, 3%), and to HIV (0/197). In total 29% of respondents (173/593) reported ever injecting drugs, but only 7% (14/197) of those entering prison for the first time reported doing so compared with 40% (157/394) of those previously in prison. Use of injected drugs was the most important predictor of antibodies to hepatitis B core antigen and hepatitis C virus. <b>Conclusions:</b> Use of injected drugs and infection with hepatitis C virus are endemic in Irish prisons. A third of prison entrants were committed to prison for the first time. Only a small number of first time entrants were infected with one or more of the viruses. These findings confirm the need for increased infection control and harm reduction measures in Irish prisons. <h3>What is already known on this topic</h3> High rates of using injected drugs, initiation of use of injected drugs, and sharing of injecting equipment occur in Irish prisons Injecting drug users have high rates of infection with hepatitis B and C viruses, and hepatitis C is endemic in injecting drug users and in Irish prisoners <h3>What this study adds</h3> The prevalence of antibodies to hepatitis B core antigen, to hepatitis C, and to HIV in prison entrants who had previously been imprisoned was similar to that found in the recent national survey of Irish prisoners, but the prevalence of these antibodies was much lower in the third of prison entrants who had never previously been in prison Tattooing in prison is an independent risk factor for hepatitis C infection in prisoners who have never used injected drugs
p53 as an Independent Prognostic Marker in Lymph Node-Negative Breast Cancer Patients
Authors: R. Silvestrini, E. Benini, M. G. Daidone, S. Veneroni, P. Boracchi, V. Cappelletti, G. D. Fronzo, U. Veronesi
Journal: JNCI Journal of the National Cancer Institute (1993)

At present, most decisions concerning the use of adjuvant therapy in lymph node-negative breast cancer patients are made on the basis of traditional factors such as tumor size, nodal status, and histopathologic features. However, prognostic factors are being investigated that could identify high-risk groups and that could better address treatment efforts for those patients. Identification of more accurate prognostic markers, such as the expression of the mutant p53 protein encoded by the p53 (also known as TP53) tumor suppressor gene, that are reproducible, easily assessable, and independent in predicting clinical outcome would have a beneficial impact on cancer treatment decisions. Purpose : Our Purpose was to analyze the predictive relevance of mutant p53 protein expression on 6-year relapse-free and overall survival in node-negative breast cancer patients in relation to menopausal status, tumor size, cell kinetics, and estrogen receptor status. Methods : Expression of mutant p53 protein was detected by an immunohistochemical technique using a 1: 50 dilution of PAb1801 monoclonal antibody on paraffin-embedded tumor specimens obtained from 256 axillary lymph nodenegative breast cancer patients, with long-term follow-up (median, 72 months). The [ 3 H]thymidine labeling index, a measure of cell kinetics, was evaluated on histologic sections after fresh tumor tissue was labeled with [ 3 H]thymidine. Estrogen receptor status was determined by the dextran-coated charcoal absorption technique. Statistical comparisons were made for levels of p53 protein expression, [ 3 H]thymidine labeling index, estrogen receptor status, tumor size, and menopausal status with respect to 6-year relapse-free survival and overall survival. Results : Overexpression of the p53 protein, defined as the presence of more than 5% positive cells, was detected in 113 (44%) of 256 tumors. Odds ratios (ORs) for multiple regression analysis of 6-year relapse-free survival were significantly higher for p53 (OR = 3.24; 95% confidence limits [CL] = 2.01–5.23) and [3H]thymidine labeling index (OR = 1.92; 95% CL = 1.19–3.12), both of which appeared to be the most relevant indicators of relapse, than for tumor size (OR = 1.49; 95% CL = 0.94–2.38) and estrogen receptor status (OR = 0.91; 95% CL = 0.55–1.51). Overexpression was found to be unrelated to menopausal status. Conclusions : Immunohistochemically detected p53 overexpression is an independent marker for shortened 6-year relapse-free and overall survival in node-negative patients with resectable breast cancers. Based on these findings, p53 overexpression should be used with other established prognostic factors, such as [ 3 H]thymidine labeling index and estrogen receptor status, to further refine the prognostic assessment of node-negative breast cancer. [J Natl Cancer Inst 85: 965–1970, 1993]
The functional role of the JAK–STAT pathway in post-infarction remodeling
Authors: H El-Adawi
Journal: Cardiovascular Research (2002)

Objectives: Recently, the Janus kinase/signal transducer and activator of transcription (JAK–STAT) signaling pathway was found to be prominently associated with activation of the autocrine loop of the heart tissue-localized renin angiotensin system (RAS). We investigated if the JAK–STAT pathway is activated in the post-myocardial infarction (MI) non-ischemic myocardium (NIM), destined to undergo remodeling and whether blockade of the pathway in vivo can modify early post-MI remodeling. Methods: We investigated the time course of tyrosine phosphorylation of JAK–STAT and gp130 proteins in the NIM of post-MI rat heart as well as the binding activity of STAT proteins to the St-domain of the angiotensinogen gene promoter. We further compared the effects of in vivo blockade of RAS by the AT1 receptor (AT1R) blocker losartan with the in vivo blockade of JAK–STAT pathway by the specific JAK2 blocker tyrphostin AG490 on certain aspects of early post-MI remodeling. Results: We showed that JAK2, STATs 1, 3, 5a and 6 and gp130 proteins are tyrosine phosphorylated as early as 5–30 min post-MI and that STATs 1, 3, and 5a remain activated up to 7 days post-MI. Gel mobility shift assay showed a strong binding activity of STAT proteins to the St-domain of angiotensinogen gene promoter in 1-day post-MI NIM. The binding was significantly reduced in rat hearts previously treated with losartan or tyrphostin AG490. Supershift experiments identified STATs 3 and 5a as specifically interacting with the St-domain. Both AT1R and JAK2 blockade resulted in significant amelioration of the increase of protein phosphatase 1 activity and decrease in basal level of p16-phospholamban that may underlie early diastolic dysfunction, as well as partial amelioration of early downregulation of Kv4.2 gene expression that may underlie increased arrhythmogenicity of 3-day post-MI heart. On the other hand, while blockade of AT1R significantly ameliorated apoptotic changes in 1-day post-MI border zone, blockade of JAK2 increased apoptosis. Conclusions: The study provides compelling evidence in favor of the linkage of the JAK–STAT pathway with the angiotensin II autocrine loop and uncovers a mechanism by which selective activation of a set of STAT proteins underlies mobilization of the gene activation program intrinsic to post-MI remodeling. It also suggests that drugs that inhibit JAK–STAT phosphorylation may provide a new approach to modify post-MI remodeling. This needs to be confirmed in long term in vivo studies in the post-MI heart.
Hospital Events Associated With Adverse Events and Substandard Care
Authors: F. Andrew Morfesis
Journal: JAMA (1991)

To the Editor.  — I do not agree that the observations by Brennan et al 1 may represent an important improvement on existing measures of quality, ie, outcome-based measures. My disagreement can be understood by considering a hypothetical premise that illustrates a significant potential bias in the article by Brennan et al.  My premise is that academic physician specialists are uncomfortable with outcome-based measures of quality of care because this puts them on equal footing with nonacademic physicians. Further, they prefer the concept of negligence-based quality assurance because this enables academic-based reviewers to insert a subtle bias in favor of teaching hospitals.  In the article by Brennan et al, a group of academic-based reviewers (or, at least, physician reviewers selected by academic-based reviewers and likely to be sympathetic to them) reviewed charts of about 50 hospitals. The reviewers were likely to be personally familiar with some of these institutions, while
Direct visualization of T lymphocytes bearing Ia antigens controlled by the I-J subregion
Authors: CR Parish, IFC McKenzie
Journal: The Journal of Experimental Medicine (1977)

Previous studies have demonstrated that I-J-subregion-controlled Ia antigens are only expressed on a small subpopulation of peripheral T lymphocytes which includes the suppressor T cells of antibody responses (6). This subpopulation of T cells cannot be detected by conventional dye-exclusion cytotoxicity tests. A sensitive rosetting procedure therefore was developed for detecting the binding of anti-Ia antibodies to T lymphocytes. This assay system, unlike the complement lysis technique, has a low background and since it represents a direct binding assay could detect noncomplement-fixing antibodies in the antisera. Anti-Ia sera were absorbed with B cells and using the rosetting procedure in genetic mapping studies the remaining antibodies were found to be directed against I-J-subregion-controlled determinants. These determinants were shown to be highly haplotype specific for H-2(k) and H-2(s) and appeared to be exclusively expressed on Ly-l.l(-), Ly2.1(+), T lymphocytes, at least some of which were suppressor T cells. Lymphoid organs differed in their content of anti-I-J-reactive cells, the hierarchy being spleen, lymph node more than thymus, bone marrow. In contrast, on a T-cell basis, a high proportion (35 percent) of the T cells in bone marrow reacted with anti-I-J antibodies, a substantial proportion (13 percent) of T cells from spleen were reactive, whereas the lymph node and thymus T-cell populations contained only a small proportion of positive cells (1-4 percent).
High Prevalence of Pulmonary Tuberculosis and Inadequate Case Finding in Rural Western Kenya
Authors: Anna H. van't Hoog, Kayla F. Laserson, Willie A. Githui, Helen K. Meme, Janet A. Agaya, Lazarus O. Odeny, Benson G. Muchiri, Barbara J. Marston, Kevin M. DeCock, Martien W. Borgdorff
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV.To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection.Residents aged 15 years and older, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum sample for culture.PTB was defined by a culture positive for Mycobacterium tuberculosis or two positive smears. Persons with PTB were offered HIV testing and interviewed on care-seeking behavior. We estimated the population-attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively.Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.
Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression
Authors: Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi
Journal: Cancer Research (2015)

Abstract PI3K–Akt signaling is critical for the development, progression, and metastasis of malignant tumors, but its role in the tumor microenvironment has been relatively little studied. Here, we report that the Akt substrate Girdin, an actin-binding protein that regulates cell migration, is expressed and activated by Akt phosphorylation in cancer-associated fibroblasts (CAF) and blood vessels within the tumor microenvironment. Lewis lung tumors grafted into mice defective in Akt-mediated Girdin phosphorylation (SA transgenic mice) exhibited a decrease in both CAF infiltration and tumor growth, compared with wild-type (WT) host control animals. Contrasting with the findings of other studies, we found that Akt-dependent phosphorylation of Girdin was not a rate-limiting step in the growth of endothelial cells. In addition, Lewis lung tumors displayed limited outgrowth when cotransplanted with CAF derived from tumor-bearing SA transgenic mice, compared with CAF derived from tumor-bearing WT mice. Collectively, our results revealed a role for Akt-mediated Girdin phosphorylation in CAF during tumor progression, highlighting the need to inhibit Akt function in both tumor cells and cells that comprise the tumor microenvironment. Cancer Res; 75(5); 813–23. ©2015 AACR.
Molecular Photoacoustic Imaging of Follicular Thyroid Carcinoma
Authors: Jelena Levi, Sri-Rajashekar Kothapalli, Sarah Bohndiek, Joon-Kee Yoon, Anca Dragulescu-Andrasi, Carsten Nielsen, Aleksandra Tisma, Sunil Bodapati, Gayatri Gowrishankar, Xinrui Yan, Carmel Chan, Daniela Starcevic, Sanjiv Sam Gambhir
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma. Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method. Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent. Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas. Clin Cancer Res; 19(6); 1494–502. ©2013 AACR.
Bexarotene via CBP/p300 Induces Suppression of NF-κB–Dependent Cell Growth and Invasion in Thyroid Cancer
Authors: Audrey Cras, Béatrice Politis, Nicole Balitrand, Diane Darsin-Bettinger, Pierre Yves Boelle, Bruno Cassinat, Marie-Elisabeth Toubert, Christine Chomienne
Journal: Clinical Cancer Research (2011)

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells.A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging.In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation.This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway.
Regulation of <i>c-Jun NH2-terminal Kinase</i> ( <i>Jnk</i>) Gene Expression during T Cell Activation
Authors: Linda Weiss, Alan J. Whitmarsh, Derek D. Yang, Mercedes Rincón, Roger J. Davis, Richard A. Flavell
Journal: The Journal of Experimental Medicine (2000)

The c-Jun NH2-terminal kinases (JNKs) are a group of mitogen-activated protein (MAP) kinases that participate in signal transduction events mediating specific cellular functions. Activation of JNK is regulated by phosphorylation in response to cellular stress and inflammatory cytokines. Here, we demonstrate that JNK is regulated by a second, novel mechanism. Induction of Jnk gene expression is required in specific tissues before activation of this signaling pathway. The in vivo and in vitro ligation of the T cell receptor (TCR) leads to induction of JNK gene and protein expression. TCR signals are sufficient to induce JNK expression, whereas JNK phosphorylation also requires CD28-mediated costimulatory signals. Therefore, both expression and activation contribute to the regulation of the JNK pathway to ensure proper control during the course of an immune response.
Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70
Authors: K. Ferenczi, J. Ohtola, P. Aubert, M. Kessler, H. Sugiyama, A.K. Somani, A.C. Gilliam, J.Z. Chen, I. Yeh, S. Matsuyama, T.S. McCormick, K.D. Cooper
Journal: British Journal of Dermatology (2010)

Background Malignant T cells in primary cutaneous T-cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis-inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses. Methods Normal (n = 10), CTCL (n = 9) and benign dermatoses (n = 13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n = 6). Results Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T-cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement. Conclusions Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis-inducing treatment modalities in the setting of intrinsic resistance to apoptosis.