tbuckley/cabot-search huggingface dataset:
Digestive Organ in the Female Reproductive Tract Borrows Genes from Multiple Organ Systems to Adopt Critical Functions
Authors: Camille Meslin, Melissa S. Plakke, Aaron B. Deutsch, Brandon S. Small, Nathan I. Morehouse, Nathan L. Clark
Journal: Molecular Biology and Evolution (2015)

Persistent adaptive challenges are often met with the evolution of novel physiological traits. Although there are specific examples of single genes providing new physiological functions, studies on the origin of complex organ functions are lacking. One such derived set of complex functions is found in the Lepidopteran bursa copulatrix, an organ within the female reproductive tract that digests nutrients from the male ejaculate or spermatophore. Here, we characterized bursa physiology and the evolutionary mechanisms by which it was equipped with digestive and absorptive functionality. By studying the transcriptome of the bursa and eight other tissues, we revealed a suite of highly expressed and secreted gene products providing the bursa with a combination of stomach-like traits for mechanical and enzymatic digestion of the male spermatophore. By subsequently placing these bursa genes in an evolutionary framework, we found that the vast majority of their novel digestive functions were co-opted by borrowing genes that continue to be expressed in nonreproductive tissues. However, a number of bursa-specific genes have also arisen, some of which represent unique gene families restricted to Lepidoptera and may provide novel bursa-specific functions. This pattern of promiscuous gene borrowing and relatively infrequent evolution of tissue-specific duplicates stands in contrast to studies of the evolution of novelty via single gene co-option. Our results suggest that the evolution of complex organ-level phenotypes may often be enabled (and subsequently constrained) by changes in tissue specificity that allow expression of existing genes in novel contexts, such as reproduction. The extent to which the selective pressures encountered in these novel roles require resolution via duplication and sub/neofunctionalization is likely to be determined by the need for specialized reproductive functionality. Thus, complex physiological phenotypes such as that found in the bursa offer important opportunities for understanding the relative role of pleiotropy and specialization in adaptive evolution.
New guide ranks success of IVF treatment centres
Authors: Colleen Shannon
Journal: BMJ (2005)

Couples seeking fertility treatment in the United Kingdom will be able to compare the success rates of different centres by using statistics published in a new directory from the Human Fertilisation and Embryology Authority (HFEA). The figures will also be available in an online database.

“This is the most comprehensive and detailed information published about UK infertility services, and we believe it's unique globally,” said Suzi Leather, the HFEA's chairwoman.

Infertility represents a considerable proportion of the workload in general practice, and aside from pregnancy it is the most common reason among women aged between 18 and 45 for consulting a GP.

Many of these …
PIK3CA/PTEN Mutations and Akt Activation As Markers of Sensitivity to Allosteric mTOR Inhibitors
Authors: Funda Meric-Bernstam, Argun Akcakanat, Huiqin Chen, Kim-Anh Do, Takafumi Sangai, Farrell Adkins, Ana Maria Gonzalez-Angulo, Asif Rashid, Katherine Crosby, Mei Dong, Alexandria T. Phan, Robert A. Wolff, Sanjay Gupta, Gordon B. Mills, James Yao
Journal: Clinical Cancer Research (2012)

Abstract Purpose: We sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance. Experimental Design: Cancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer cells and patients with neuroendocrine tumor (NET) were treated with rapalogs and Akt phosphorylation was assessed. Results: Thirty-one cell lines were rapamycin sensitive (RS) and 12 were relatively rapamycin resistant (RR; IC50 &amp;gt; 100 nmol/L). Cells with PIK3CA and/or PTEN mutations were more likely to be RS (P = 0.0123). Akt phosphorylation (S473 and T308) was significantly higher in RS cells (P &amp;lt; 0.0001). Rapamycin led to a significantly greater pathway inhibition and greater increase in p-Akt T308 (P &amp;lt; 0.0001) and p-Akt S473 (P = 0.0009) in RS cells. Rapamycin and everolimus significantly increased Akt phosphorylation but inhibited growth in an in vivo NET model (BON). In patients with NETs treated with everolimus and octreotide, progression-free survival correlated with p-Akt T308 in pretreatment (R = 0.4762, P = 0.0533) and on-treatment tumor biopsies (R = 0.6041, P = 0.0102). Patients who had a documented partial response were more likely to have an increase in p-Akt T308 with treatment compared with nonresponders (P = 0.0146). Conclusion: PIK3CA/PTEN genomic aberrations and high p-Akt levels are associated with rapamycin sensitivity in vitro. Rapamycin-mediated Akt activation is greater in RS cells, with a similar observation in patients with clinical responses on exploratory biomarker analysis; thus feedback loop activation of Akt is not a marker of resistance but rather may function as an indicator of rapamycin activity. Clin Cancer Res; 18(6); 1777–89. ©2012 AACR.
Reducing Model Complexity of the General Markov Model of Evolution
Authors: V. Jayaswal, F. Ababneh, L. S. Jermiin, J. Robinson
Journal: Molecular Biology and Evolution (2011)

The selection of an optimal model for data analysis is an important component of model-based molecular phylogenetic studies. Owing to the large number of Markov models that can be used for data analysis, model selection is a combinatorial problem that cannot be solved by performing an exhaustive search of all possible models. Currently, model selection is based on a small subset of the available Markov models, namely those that assume the evolutionary process to be globally stationary, reversible, and homogeneous. This forces the optimal model to be time reversible even though the actual data may not satisfy these assumptions. This problem can be alleviated by including more complex models during the model selection. We present a novel heuristic that evaluates a small fraction of these complex models and identifies the optimal model.
Acute respiratory distress syndrome or pulmonary oedema?
Authors: Yi-Ting Chen, Wei-Kai Wu, Yung-Hsiang Hsu
Journal: Thorax (2015)

A 51-year-old woman who was a smoker presented to our emergency department with acute respiratory distress. Two months previously she had developed dyspnoea aggravated by exertion and a dry cough. Orthopnoea, leg oedema and resting dyspnoea had deteriorated 3 days prior to this presentation. There was no chest pain, fever, anorexia, abdominal pain or body weight loss. On examination she was obese and normotensive. A non-rebreathing oxygen mask was necessary to maintain her oxygen saturation (Spo2) at >90%. She had diffuse lung crackles, elevated jugular veins and pretibial pitting oedema. There was no heart murmur or gallop sounds. The ECG showed sinus tachycardia of 115 bpm. Routine blood tests showed no remarkable findings except D-dimer of 2019 ng/mL. The serum procalcitonin …
Time-to-Treatment Failure As the Primary End Point of a First-Line Advanced Gastric Cancer Randomized Trial: How Confused Would You Want Us to Be?
Authors: Elena Elimova, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: We read the report by Guimbaud et al 1 with interestandappreciatetheirenormousefforttoconductthistrial.We, however, remain concerned regarding the study design, chosen primary end point, the two regimens investigated, and finally, the conclusions drawn. In general, both regimens performed poorly (the median duration of therapy was only 4 months) compared with previouslyreportedregimensdocetaxel,cisplatin,andfluorouacil;cisplatin andfluorouacil; or S1/cisplatin. 2,3 The overall grade 3 or 4 toxicity rate was unacceptably high (84% for epirubicin, cisplatin, and fluorouracil [ECF] and 69% for fluorouracil, leucovorin, and irinotecan [FOLFIRI]).Treatment-relatedmortalityofapproximately4%isalso high and not acceptable. Based on these results, one could argue that none of these two regimens should be recommended to our patients with advanced gastric cancer in the first-line setting. Contribution of epirubicin to prolongation of overall survival (OS) has never been documented and similarly, irinotecan never produced prolongation
Patient-clinician communication about end-of-life care for Dutch and US patients with COPD
Authors: D.J.A. Janssen, J.R. Curtis, D.H. Au, M.A. Spruit, L. Downey, J.M.G.A. Schols, E.F.M. Wouters, R.A. Engelberg
Journal: European Respiratory Journal (2011)

Improving patient–clinician communication about end-of-life care is important in order to enhance quality of care for patients with chronic obstructive pulmonary disease (COPD). Our objective was to compare quality of patient–clinician communication about end-of-life care, and endorsement of barriers and facilitators to this communication in the Netherlands and the USA. The present study was an analysis of survey data from 122 Dutch and 391 US outpatients with COPD. We compared quality of patient–clinician communication about end-of-life care (Quality of Communication questionnaire) and barriers and facilitators to communication about end-of-life care (Barriers and Facilitators Questionnaire) between the Netherlands and the USA, controlling for patients’ demographic and illness characteristics. Although Dutch patients in this study had worse lung function and disease-specific health status than US patients, Dutch patients reported lower quality of communication about end-of-life care (median score 0.0 (interquartile range 0.0–2.0) versus 1.4 (0.0–3.6); adjusted p&lt;0.005). Clinicians in both countries rarely discussed life-sustaining treatment preferences, prognoses, dying processes or spiritual issues. Quality of communication about end-of-life care needs to improve in the Netherlands and the USA. Future studies to improve this communication should be designed to take into account international differences and patient-specific barriers and facilitators to communication about end-of-life care.
Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype
Authors: Tan Sy, Chuang Ss, Tang T, Tan L, Ko Yh, Chuah Kl, Ng Sb, Chng Wj, Gatter K, Loong F, Liu Yh, Hosking P, Cheah Pl, Teh Bt, Tay K, Koh M, Lim St
Journal: Leukemia (2013)
QT interval prolongation as predictor of sudden death in patients with myocardial infarction.
Authors: P J Schwartz, S Wolf
Journal: Circulation (1978)

Fifty-five patients with recent myocardial infarction and 55 healthy controls, matched for age, sex, race, height, weight, education and job, had an electrocardiogram taken every two months for seven years. Twenty-eight patients and one control had a sudden cardiac death. The QTc (mean of all values recorded) was found prolonged in one control (2%), five of 27 surviving patients (18%) and in 16 of 28 patients who had sudden death (57%). The difference between surviving and sudden death patients is significant (P less than 0.01). It is interesting that the only control with a long QT was the one when died suddenly of myocardial infarction. Among patients with previous myocardial infarction a prolonged QTc constitutes a 2.16 times greater risk for sudden death. We conclude that a constant prolongation of QTc in patients with myocardial infarction may help, with other risk factors, in defining a subgroup at higher risk for sudden death.
Estrogen-receptor-directed neoadjuvant therapy for breast cancer: Results of a randomised trial using formestane and methotrexate, mitozantrone and mitomycin C (MMM) chemotherapy
Authors: J.-C. Gazet, H.T. Ford, R. Gray, C. McConkey, R. Sutcliffe, J. Quilliam, V. Makinde, S. Lowndes, R.C. Coombes
Journal: Annals of Oncology (2001)
Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse.
Authors: M Murakami, T Tsubata, R Shinkura, S Nisitani, M Okamoto, H Yoshioka, T Usui, S Miyawaki, T Honjo
Journal: The Journal of Experimental Medicine (1994)

About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases.
Cost effectiveness of vaccination against pandemic influenza in European countries: mathematical modelling analysis
Authors: A. K. Lugner, M. van Boven, R. de Vries, M. J. Postma, J. Wallinga
Journal: BMJ (2012)

<b>Objective</b> To investigate whether a single optimal vaccination strategy exists across countries to deal with a future influenza pandemic by comparing the cost effectiveness of different strategies in various pandemic scenarios for three European countries. <b>Design</b> Economic and epidemic modelling study. <b>Settings</b> General populations in Germany, the Netherlands, and the United Kingdom. <b>Data sources</b> Country specific patterns of social contact and demographic data. <b>Model</b> An age structured susceptible-exposed-infected-recovered transmission model that describes how an influenza A virus will spread in the populations of Germany, the Netherlands, and the United Kingdom. <b>Interventions</b> Comparison of four vaccination strategies: no vaccination, blanket vaccination, vaccination of elderly people (≥65 years), and vaccination of high transmitters (5-19 years). The four strategies were evaluated for scenarios in which a vaccine became available early or at the peak of the pandemic, and in which either everyone was initially susceptible or older age groups had pre-existing immunity. <b>Main outcome measure</b> Cost per quality adjusted life years (QALYs) gained. <b>Results</b> All vaccination strategies were cost effective (incremental cost per QALY gained, comparing intervention with non-intervention). In scenarios where the vaccine became available at the peak of the pandemic and there was pre-existing immunity among elderly people the incremental cost effectiveness ratios for vaccinating high transmitters were €7325 (£5815; $10 470) per QALY gained for Germany, €10 216 per QALY gained for the Netherlands, and €7280 per QALY gained for the United Kingdom. The most cost effective strategy not only differed across the pandemic scenarios but also between countries. Specifically, when the vaccine was available early in the pandemic and there was no pre-existing immunity, in Germany it would be most cost effective to vaccinate elderly people ( €940 per QALY gained), whereas it would be most cost effective to vaccinate high transmitters in both the Netherlands (€525 per QALY gained) and the United Kingdom (€163 per QALY gained). This difference in optimal strategies was due to differences in the demographic characteristics of the countries: Germany has a significantly higher proportion of elderly people compared with the Netherlands and the United Kingdom. <b>Conclusions</b> No single vaccination strategy was most cost effective across countries. With aging populations, pre-existing immunity in particular could be of crucial importance for the cost effectiveness of options to mitigate a future influenza pandemic.
Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.
Authors: T Zhou, C K Edwards, J D Mountz
Journal: The Journal of Experimental Medicine (1995)

T cell dysfunction and thymic involution are major immunologic abnormalities associated with aging. Fas (CD95) is a bifunctional molecule that is critical for apoptosis and stimulation during T cell development, but the role of Fas during aging has not been determined. Fas expression and function on T cells from old (22-26-mo-old) mice was compared with young (2-mo-old) mice and old CD2-fas-transgenic mice. Fas expression and ligand-induced apoptosis were decreased on T cells from old mice compared with young mice. This correlated with an age-related increase in CD44+Fas- T cells. There was a marked decrease in the proliferation of T cells from old mice after anti-CD3 stimulation compared with young mice. Anti-CD3-stimulated T cells from young mice exhibited increased production of interleukin (IL)-2 and decreased production of interferon-gamma and IL-10 compared with old mice. There was an age-related decrease in the total thymocyte count from 127 +/- 10 cells in young mice compared with 26 +/- 8 x 10(6) in old mice. In 26-mo-old CD2-fas-transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation, and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis, and that the CD2-fas transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.
Absence of K cells in human gut mucosa.
Authors: R Clancy, A Pucci
Journal: Gut (1978)

Lymphocytes have been isolated from human rectal biopsies in numbers sufficient for microassay procedures. No antibody-dependent cell-mediated cytotoxic (ADCC) activity could be detected in normal or inflamed human gut mucosa, using two assay systems which detect predominantly K cell activity. The tissue localisation and circulation characteristics of K cells require definition before establishing their role as an efferent immunological mechanism.
Antisense Oligodeoxynucleotides Directed Against Kv1.5 mRNA Specifically Inhibit Ultrarapid Delayed Rectifier K <sup>+</sup> Current in Cultured Adult Human Atrial Myocytes
Authors: Jianlin Feng, Barbara Wible, Gui-Rong Li, Zhiguo Wang, Stanley Nattel
Journal: Circulation Research (1997)

Several cloned K+ channel subunits are candidates to underlie macroscopic currents in the human heart, but direct evidence bearing on their role is lacking. The Kv1.5 K+ channel subunit has been suggested to play a potential role in human cardiac ultrarapid delayed rectifier (IKur) and transient outward (Ito) currents. To evaluate the role of proteins encoded by the Kv1.5 gene, we incubated cultured human atrial myocytes for 48 hours in medium containing antisense phosphorothioate oligodeoxynucleotides directed against octodecameric segments of the Kv1.5 mRNA coding sequence, the same concentration of homologous oligodeoxynucleotides with four mismatch mutations, or vehicle (control group). Cells exposed to antisense showed a highly significant (approximately 50%) reduction in IKur whether measured by step current at the end of a 400-millisecond depolarizing pulse, tail current at -20 mV, or current sensitive to a concentration of 4-aminopyridine (50 mumol/L) that is highly selective for IKur compared with control cells or cells exposed to mismatch oligodeoxynucleotides. In contrast, Ito was not different among the three experimental groups. When cultured human ventricular myocytes were exposed to Kv1.5 antisense oligodeoxynucleotides with the same controls, no changes occurred in either Ito or the sustained current at the end of a depolarizing pulse. We conclude that Kv1.5 channel subunits are essential to the expression of IKur and do not play a role in Ito in cultured human atrial myocytes. These studies provide the first direct evidence with an antisense approach for the equivalence between a macroscopic cardiac K+ current and a cloned K+ channel subunit and offer insights into the molecular electrophysiology of the human heart.
Acute acral pustulosis
Authors: T.J. HOFFMANN, ANNE KETTLER, SUZANNE BRUCE
Journal: British Journal of Dermatology (1989)

We report a patient with a pustular eruption in an acral distribution that developed abruptly 4 days after a streptococcal pharyngitis. The histology showed an intraepidermal vesicle filled with neutrophils with an underlying lymphocytic vasculitis. Direct immunofluorescence demonstrated heavy deposition of C3 within the vessel walls. In addition, circulating immune complexes were found.
710 Different free fatty acids (FFA) affect steatosis extent and hepatocyte apoptosis. Evidence from an in vitro study
Authors: M. Ricchi, M.R. Odoardi, L. Carulli, M.L. Bormioli, C. Anzivino, M. Bertolotti, A. Lonardo, N. Carulli, P. Loria
Journal: Journal of Hepatology (2006)
Oncogenic Potential of the <i>miR-106-363</i> Cluster and Its Implication in Human T-Cell Leukemia
Authors: Séverine Landais, Sébastien Landry, Philippe Legault, Eric Rassart
Journal: Cancer Research (2007)

Abstract We previously reported the identification of the Kis2 common retrovirus integration site, located on mouse chromosome X, in radiation leukemia virus–induced T-cell leukemias. Tumors with a provirus at the Kis2 locus overexpressed a novel noncoding RNA (ncRNA) with a complex splicing pattern and no polyA tail. Database upgrade revealed the presence of a microRNA (miRNA) cluster, miR-106-363, just downstream of the Kis2 ncRNAs. We found that Kis2 ncRNAs are the pri-miRNA of miR-106-363, and we present evidence that Kis2 ncRNA overexpression in mouse tumors results in miR-106a, miR-19b-2, miR-92-2, and miR-20b accumulation. We show the oncogenic potential of those miRNAs in anchorage independence assay and confirm pri-miR-106-363 overexpression in 46% of human T-cell leukemias tested. This overexpression contributes in rising miR-92 and miR-19 levels, as this is the case for miR-17-92 cluster overexpression. Furthermore, we identified myosin regulatory light chain–interacting protein, retinoblastoma-binding protein 1-like, and possibly homeodomain-interacting protein kinase 3 as target genes of this miRNA cluster, which establishes a link between these genes and T-cell leukemia for the first time. [Cancer Res 2007;67(12):5699–707]