tbuckley/cabot-search huggingface dataset:
Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development
Authors: Morten T. Venø, Thomas B. Hansen, Susanne T. Venø, Bettina H. Clausen, Manuela Grebing, Bente Finsen, Ida E. Holm, Jørgen Kjems
Journal: Genome biology (2015)

Recently, thousands of circular RNAs (circRNAs) have been discovered in various tissues and cell types from human, mouse, fruit fly and nematodes. However, expression of circRNAs across mammalian brain development has never been examined. Here we profile the expression of circRNA in five brain tissues at up to six time-points during fetal porcine development, constituting the first report of circRNA in the brain development of a large animal. An unbiased analysis reveals a highly complex regulation pattern of thousands of circular RNAs, with a distinct spatio-temporal expression profile. The amount and complexity of circRNA expression was most pronounced in cortex at day 60 of gestation. At this time-point we find 4634 unique circRNAs expressed from 2195 genes out of a total of 13,854 expressed genes. Approximately 20 % of the porcine splice sites involved in circRNA production are functionally conserved between mouse and human. Furthermore, we observe that "hot-spot" genes produce multiple circRNA isoforms, which are often differentially expressed across porcine brain development. A global comparison of porcine circRNAs reveals that introns flanking circularized exons are longer than average and more frequently contain proximal complementary SINEs, which potentially can facilitate base pairing between the flanking introns. Finally, we report the first use of RNase R treatment in combination with in situ hybridization to show dynamic subcellular localization of circRNA during development. These data demonstrate that circRNAs are highly abundant and dynamically expressed in a spatio-temporal manner in porcine fetal brain, suggesting important functions during mammalian brain development.
Comparative Genomics and Regulatory Evolution: Conservation and Function of the Chs and Apetala3 Promoters
Authors: Marcus A. Koch, Bernd Weisshaar, Juergen Kroymann, Bernhard Haubold, Thomas Mitchell-Olds
Journal: Molecular Biology and Evolution (2001)

DNA sequence variations of chalcone synthase (Chs) and Apetala3 gene promoters from 22 cruciferous plant species were analyzed to identify putative conserved regulatory elements. Our comparative approach confirmed the existence of numerous conserved sequences which may act as regulatory elements in both investigated promoters. To confirm the correct identification of a well-conserved UV-light-responsive promoter region, a subset of Chs promoter fragments were tested in Arabidopsis thaliana protoplasts. All promoters displayed similar light responsivenesses, indicating the general functional relevance of the conserved regulatory element. In addition to known regulatory elements, other highly conserved regions were detected which are likely to be of functional importance. Phylogenetic trees based on DNA sequences from both promoters (gene trees) were compared with the hypothesized phylogenetic relationships (species trees) of these taxa. The data derived from both promoter sequences were congruent with the phylogenies obtained from coding regions of other nuclear genes and from chloroplast DNA sequences. This indicates that promoter sequence evolution generally is reflective of species phylogeny. Our study also demonstrates the great value of comparative genomics and phylogenetics as a basis for functional analysis of promoter action and gene regulation.
Estrogen Therapy and Coronary-Artery Calcification
Authors: JoAnn E. Manson, Matthew A. Allison, Jacques E. Rossouw, J. Jeffrey Carr, Robert D. Langer, Judith Hsia, Lewis H. Kuller, Barbara B. Cochrane, Julie R. Hunt, Shari E. Ludlam, Mary B. Pettinger, Margery Gass, Karen L. Margolis, Lauren Nathan, Judith K. Ockene, Ross L. Prentice, John Robbins, Marcia L. Stefanick
Journal: New England Journal of Medicine (2007)

Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.
Thoracic Oncology HERMES syllabus: setting the basis for thoracic oncology training in Europe: Table 1–
Authors: Fernando Gamarra, Paolo Boffetta, Dirk De Ruysscher, Enriqueta Felip, Mina Gaga, Bogdan Grigoriu, Rudolf M Huber, Sam M Janes, Charles Hugo Marquette, Gilbert Massard, Julie-Lyn Carrillo Noel, Jean-Paul Sculier, Anne-Pascale Meert
Journal: European Respiratory Journal (2013)

Background: The mechanism of exaggerated airway narrowing in asthma is unclear and there is little to no biological data on whether increased airway smooth muscle (ASM) increases narrowing capacity.  Objective: Determine whether increased airway narrowing in asthma is related to increased ASM mass.  Methods: Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported doctor-diagnosed asthma (n=5) or had no history of asthma (n=8). In vitro airway narrowing in response to acetylcholine (3x10-6M to 3x10-3M) was assessed to determine maximal bronchoconstriction and sensitivity. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the ASM layer.  Results: Airways from the asthma group had increased ASM (P=0.014), greater maximal airway narrowing (P=0.003) but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer (r=0.58, P=0.039) but was not related to any other morphological parameter including inner and outer wall dimensions.  Conclusions: Results suggest that greater ASM mass in asthma contributes to increased maximal airway narrowing in vivo. In contrast, properties of the ASM may not determine increased airway sensitivity.
Variation in KLK genes, prostate-specific antigen and risk of prostate cancer
Authors: Jiyoung Ahn, Sonja I Berndt, Sholom Wacholder, Peter Kraft, Adam S Kibel, Meredith Yeager, Demetrius Albanes, Edward Giovannucci, Meir J Stampfer, Jarmo Virtamo, Michael J Thun, Heather Spencer Feigelson, Geraldine Cancel-Tassin, Olivier Cussenot, Gilles Thomas, David J Hunter, Joseph F Fraumeni, Robert N Hoover, Stephen J Chanock, Richard B Hayes
Journal: Nature Genetics (2008)
THE DIFFERENTIAL TOXICITY OF AMMONIUM SALTS
Authors: Kenneth S Warren
Journal: Journal of Clinical Investigation (1958)

Intravenous LD50's were determined in young Swiss albino mice, weighing 18 to 22 Gm. (average, 19.7 Gm.). One ml. of isotonic saline containing the ammonium compounds (reagent grade) in varying concentrations was injected into a tail vein during an average time of 1.9 seconds. The lethal effect was determined in 10 animals for each of three to five concentration levels. The mice were observed continually until all signs of acute toxicity disappeared and then were examined during the course of several days for the appearance of any latent toxicity. Blood pH was determined with a Beckman Model GS
Lovastatin inhibits mesangial cell proliferation via p27Kip1.
Authors: Y Terada, S Inoshita, O Nakashima, T Yamada, M Kuwahara, S Sasaki, F Marumo
Journal: Journal of the American Society of Nephrology (1998)

Mesangial cell proliferation is a key feature of glomerulonephritis. The hydroxymethylglutaryl-coenzyme A reductase inhibitor lovastatin is known to inhibit cell cycle progression. To determine the inhibitory mechanisms of mesangial cell proliferation by lovastatin, the cyclin-dependent kinase (CDK) activity, and expression of CDK inhibitor (p27Kip1, p21Cip1, and p16INK4) mRNA and protein were measured. Lovastatin inhibited phosphorylation of retinoblastoma protein and mesangial cell proliferation dose dependently. Lovastatin increased the p27Kip1 protein level but produced no changes in the abundance of the p27Kip1 mRNA level both in the presence and absence of mitogens. Treatment with lovastatin revealed the increment of both CDK2- and CDK4-bound-p27Kip1. The experiment using antisense oligonucleotide against p27Kip1 showed significant amelioration of lovastatin-induced cell cycle arrest. Lovastatin reduced both platelet-derived growth factor-stimulated CDK2 and CDK4 kinase activities. In conclusion, lovastatin inhibited mesangial proliferation via translational upregulation or impairment of p27Kip1 protein degradation. Lovastatin serves as a potential therapeutic approach to mesangial proliferative disease.
The Genetic Revolution and Human Rights; Human Genetics—Choice and Responsibility
Authors: Imre Szebik
Journal: BMJ (2000)

Ed Justine Burley 

Oxford University Press, £7.99, 220

ISBN 0 19 286201 4

British Medical Association 

Oxford University Press, £7.99, pp 236

ISBN 0 19 288055 1

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Genetics and cloning are “hot” topics in Western society, and they trigger interesting and thought provoking discussions. In The Genetic Revolution and Human Rights , Justine Burley has collected outstanding scholars to discuss Dolly the sheep, the advantages of cloning, and the importance of …

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RESPONSIBILITIES OF MEDICAL PROFESSION IN HEALTH PROGRAM OF PUBLIC SCHOOLS
Authors: FRED MOORE
Journal: JAMA (1930)

Children are legally required to attend school usually not less than ten years. The mere fact of assemblage immediately creates a health problem. A proper environment for building and grounds should be the first consideration. The character of the building with reference to light, ventilation, heating and capacity is equally important. These may be perfect but are greatly offset if there are in attendance either teachers or children whose physical condition is a menace. Recently a director of a consolidated rural school telephoned to me and described this situation: "The new term of school opened this morning. At midday a boy who had been in a room with forty children throughout the forenoon complained of illness. He was taken to a doctor and found to be in the eruptive stage of scarlet fever. Now what shall we do? Should the children be vaccinated? Should the building be fumigated? Should school
Pitfalls of Retrospective and Nonrandomized Comparison of Treatment Modalities
Authors: Ajay P. Sandhu
Journal: Journal of Clinical Oncology (2010)

The study by Zelefsky et al 1 is a large but retrospective study assessing the distant metastases rates in patients treated with radical prostatectomy (RP) or external-beam radiotherapy (EBRT) for localized prostate cancer.Although the title of the article suggests that clinical cohorts were adjusted for case mix, the clinical characteristics of two groups seem grossly different.The median age was higher in the EBRT arm versus the RP arm (69 v 60 years, respectively).The median total prostate-specific antigen was 7.6 ng/mL in the EBRT arm versus 6.2 ng/mL in the RP arm.Nine percent of patients in the EBRT arm versus 4% in the RP arm had clinical stage T3 disease.A similar trend was seen in Gleason score; 51% of patients had scores of 7 or higher in the EBRT group versus 34% of patients in the surgical group.Given these differences, the results should not be surprising.RT was delivered with intensity-modulated radiation therapy, but modern image-guided radiation therapy techniques were not available then.These techniques are expected to affect outcomes in localized prostate cancer not only by reduction in adverse effects but also by improving local tumor control by accurate localization of the target throughout radiotherapy treatment.The authors conclude that results may be confounded by differences in the use (76% v 43% in the RP and EBRT arms, respectively) and timing (median time, 13 v 69 months in the RP and EBRT arms, respectively) of salvage therapy after biochemical recurrence.However, there is little mention (other than Gleason score) about the worst clinical characteristics, as mentioned earlier, in the EBRT arm.It is also important to highlight that salvage therapy after RP (ie, EBRT) can be potentially curative, unlike salvage androgen-deprivation therapy after EBRT.The number of patients receiving adjuvant radiation therapy after RP is missing, which could have altered the outcome given the updated results of the Southwest Oncology Group trial, 2 showing advantage for metastasisfree survival.
The search for an HIV cure: tackling latent infection
Authors: Stephen J Kent, Jeanette C Reece, Janka Petravic, Alexey Martyushev, Marit Kramski, Robert De Rose, David A Cooper, Anthony D Kelleher, Sean Emery, Paul U Cameron, Sharon R Lewin, Miles P Davenport
Journal: The Lancet Infectious Diseases (2013)
MiR-15a and MiR-16 Control Bmi-1 Expression in Ovarian Cancer
Authors: Resham Bhattacharya, Milena Nicoloso, Rochelle Arvizo, Enfeng Wang, Angelica Cortez, Simona Rossi, George A. Calin, Priyabrata Mukherjee
Journal: Cancer Research (2009)

Oncogenic activation of Bmi-1 is found in a wide variety of epithelial malignancies including ovarian cancer, yet a specific mechanism for overexpression of Bmi-1 has not been determined. Thus, realizing the immense pathologic significance of Bmi-1 in cancer, we wanted to investigate if microRNA (miRNA) aberrations played a role in the regulation of Bmi-1 in ovarian cancer. In this report, we identify two miRNAs, miR-15a and miR-16, that are underexpressed in ovarian cell lines and in primary ovarian tissues. We show that these miRNAs directly target the Bmi-1 3' untranslated region and significantly correlate with Bmi-1 protein levels in ovarian cancer patients and cell lines. Furthermore, Bmi-1 protein levels are downregulated in response to miR-15a or miR-16 expression and lead to significant reduction in ovarian cancer cell proliferation and clonal growth. These findings suggest the development of therapeutic strategies by restoring miR-15a and miR-16 expression in ovarian cancer and in other cancers that involve upregulation of Bmi-1.
Detection of intracranial arteriovenous fistula by two-dimensional ultrasonography.
Authors: A R Snider, S J Soifer, N H Silverman
Journal: Circulation (1981)

Three newborn infants who had severe congestive heart failure caused by an arteriovenous malformation of the vein of Galen were evaluated by two-dimensional ultrasonography. Examination of the heart from standard echocardiographic planes showed right atrial and right ventricular dilatation. The superior vena cava, ascending aorta and the vessels to the head and neck were enlarged. Contrast two-dimensional echocardiography from a peripheral vein showed right-to-left atrial shunting and early superior vena cava recirculation. With the transducer positioned in the anterior fontanel or against the temporal bone, two-dimensional sector scans of the brain were obtained in the coronal, sagittal and transverse planes. A large echo-free space that represented an aneurysm of the vein of Galen was seen within the brain. During contrast injection into a peripheral vein, microcavitations that passed from right to left at the atrial level were seen filling the vein of Galen aneurysm. In two infants in whom beryllium wire was placed in the fistula to induce thrombosis, postoperative ultrasonography showed a dense mass of echoes arising from the wire and persistent left-to-right shunting through the fistula. In infants presenting in the first week of life with congestive heart failure and cyanosis of unknown etiology, two-dimensional ultrasonography provides a rapid, safe method for detecting intracranial arteriovenous malformation.
Human Papillomavirus (HPV)-Specific T-cells Recognizing Dominant E2/E6 Epitopes Elicit Reduced IFN-γ in Patients with Recurrent Respiratory Papillomatosis (RRP)
Authors: E. James, J.A. DeVoti, D.W. Rosenthal, L.J. Hatam, B.M. Steinberg, A. Abramson, W.W. Kwok, V.R. Bonagura
Journal: Journal of Allergy and Clinical Immunology (2010)
Human Rhinovirus 1B Exposure Induces Phosphatidylinositol 3-Kinase–dependent Airway Inflammation in Mice
Authors: Dawn C. Newcomb, Umadevi S. Sajjan, Deepti R. Nagarkar, Qiong Wang, Suparna Nanua, Ying Zhou, Christina L. McHenry, Kenneth T. Hennrick, Wan C. Tsai, J. Kelley Bentley, Nicholas W. Lukacs, Sebastian L. Johnston, Marc B. Hershenson
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Infection with rhinovirus (RV) triggers exacerbations of asthma and chronic obstructive lung disease.Objectives: We sought to develop a mouse model of RV employing RV1B, a minor group serotype that binds to the low-density lipoprotein receptor.Methods: C57BL/6 mice were inoculated intranasally with RV1B, replication-deficient ultraviolet (UV)-irradiated RV1B, or RV39, a major group virus.Measurements and Main Results: Viral RNA was present in the lungs of RV1B-treated mice, but not in those exposed to UV-irradiated RV1B or RV39. Lung homogenates of RV-treated mice contained infectious RV 4 days after inoculation. RV1B exposure induced neutrophilic and lymphocytic airway inflammation, as well as increased lung expression of KC, macrophage-inflammatory protein-2, and IFN-α and IFN-β. RV1B-exposed mice showed airway hyperresponsiveness 1 and 4 days after inoculation. UV-irradiated RV1B induced modest neutrophilic airway inflammation and hyperresponsiveness 1 day after exposure. Both RV1B and UV-irradiated RV1B, but not RV39, increased lung phosphorylation of Akt. Confocal immunofluorescence showed colocalization of RV1B and phospho-Akt in the airway epithelium. Finally, pretreatment with the phosphatidylinositol 3-kinase inhibitor LY294002 attenuated chemokine production and neutrophil infiltration.Conclusions: We conclude that RV1B induces airway inflammation in vivo. Evidence is presented that viral replication occurs in vivo and is required for maximal responses. On the other hand, viral replication was not required for a subset of RV-induced responses, including neutrophilic inflammation, airway hyperresponsiveness, and Akt phosphorylation. Finally, phosphatidylinositol 3-kinase/Akt signaling is required for maximal RV1B-induced airway neutrophilic inflammation, likely via its essential role in virus internalization.
Exacerbation of isoniazid induced peripheral neuropathy by pyridoxine.
Authors: M Nisar, S W Watkin, R C Bucknall, R A Agnew
Journal: Thorax (1990)

Mycobacterium kansasii was isolated from an area of cavitating pneumonia in a man with rheumatoid arthritis. Standard antituberculosis treatment, including isoniazid 300 mg daily, had to be stopped because of peripheral neuropathy. The patient, a slow acetylator, subjectively deteriorated despite withdrawal of isoniazid and treatment with pyridoxine 150 mg daily. Improvement occurred only after the pyridoxine had also been withdrawn. Pyridoxine may cause peripheral neuropathy and this case illustrates the need for caution in the use of this vitamin in the prevention and treatment of isoniazid induced peripheral neuropathy.
Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.
Authors: P Simpson
Journal: Journal of Clinical Investigation (1983)

We have shown recently that norepinephrine stimulates muscle cell hypertrophy in primary cultures from the neonatal rat ventricle and that this stimulation is not blocked by the beta adrenergic antagonist propranolol. The present study was done to define the adrenergic specificity of the myocyte hypertrophic response to norepinephrine. 90% pure, single-cell cultures of nongrowing myocytes were maintained in serum-free medium 199 with transferin and insulin. Myocyte size was quantitated 48 h after addition of adrenergic agents, by measuring cell volume, cell surface area, and cell protein. L-norepinephrine increased myocyte size to a maximum 150% of control; half-maximum effect was obtained at a concentration of 0.2 microM. This increase in cell size was inhibited by the nonselective alpha adrenergic antagonist phentolamine and by the alpha 1 adrenergic antagonists prazosin and terazosin; it was not inhibited by propranolol or by the alpha 2 adrenergic antagonist yohimbine. The beta adrenergic agonist isoproterenol did not increase cell size. Thus, norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response.
Impact of Epithelial Organization on Myc Expression and Activity—Response
Authors: David Simpson, Senthil Muthuswamy, William P. Tansey
Journal: Cancer Research (2012)

We agree with Partanen and colleagues that both their original published work ([1][1]) and ours ([2][2]) show that epithelial architecture suppresses c-Myc and that the fundamental point of disagreement between our studies relates to the mechanism through which this occurs. Klefstrom argues that
Individual variability in human tibia lead concentration.
Authors: A C Todd, P J Parsons, S Tang, E L Moshier
Journal: Environmental Health Perspectives (2001)

Our aims in this study were to determine proximal-distal variability in adult human tibia lead concentration via electrothermal atomization atomic absorption spectrometry (ETAAS) and to determine whether there were any differences between core and surface tibia lead concentrations. We analyzed duplicate core and surface tibia samples for lead at multiple proximal-distal sections on 10 adult human cadaver legs. Dried bone samples were digested in nitric acid using microwave-assisted heating, and lead content was determined by ETAAS with Zeeman background correction. Lead concentrations in nine tibiae (one tibia was excluded because some of the data were compromised) ranged from 3.1 to 27.9 microg lead/g of dry bone. Both core and surface tibia lead concentrations were lower at the proximal and distal ends of the tibia. Surface tibia lead was approximately 5 microg/g greater than core tibia lead in six tibiae with relatively low lead concentration, and 8 microg/g greater in three tibiae with relatively high lead concentration. The difference between core and surface tibia lead was independent of proximal-distal tibia location. We conclude that these nine human tibiae showed a greater surface tibia lead concentration than core tibia lead concentration. This observation has consequences for the noninvasive measurement of tibia lead via K-shell and L-shell X-ray fluorescence.