tbuckley/cabot-search huggingface dataset:
Recent Evolution in<i>Rattus norvegicus</i>Is Shaped by Declining Effective Population Size
Authors: Eva E Deinum, Daniel L Halligan, Rob W Ness, Yao-Hua Zhang, Lin Cong, Jian-Xu Zhang, Peter D Keightley
Journal: Molecular Biology and Evolution (2015)

The brown rat, Rattus norvegicus, is both a notorious pest and a frequently used model in biomedical research. By analyzing genome sequences of 12 wild-caught brown rats from their presumed ancestral range in NE China, along with the sequence of a black rat, Rattus rattus, we investigate the selective and demographic forces shaping variation in the genome. We estimate that the recent effective population size (Ne) of this species = [Formula: see text], based on silent site diversity. We compare patterns of diversity in these genomes with patterns in multiple genome sequences of the house mouse (Mus musculus castaneus), which has a much larger Ne. This reveals an important role for variation in the strength of genetic drift in mammalian genome evolution. By a Pairwise Sequentially Markovian Coalescent analysis of demographic history, we infer that there has been a recent population size bottleneck in wild rats, which we date to approximately 20,000 years ago. Consistent with this, wild rat populations have experienced an increased flux of mildly deleterious mutations, which segregate at higher frequencies in protein-coding genes and conserved noncoding elements. This leads to negative estimates of the rate of adaptive evolution (α) in proteins and conserved noncoding elements, a result which we discuss in relation to the strongly positive estimates observed in wild house mice. As a consequence of the population bottleneck, wild rats also show a markedly slower decay of linkage disequilibrium with physical distance than wild house mice.
A low-cost open-source SNP genotyping platform for association mapping applications.
Authors: Stuart J Macdonald, Tomi Pastinen, Anne Genissel, Theodore W Cornforth, Anthony D Long
Journal: Genome biology (2005)

Abstract Association mapping aimed at identifying DNA polymorphisms that contribute to variation in complex traits entails genotyping a large number of single-nucleotide polymorphisms (SNPs) in a very large panel of individuals. Few technologies, however, provide inexpensive high-throughput genotyping. Here, we present an efficient approach developed specifically for genotyping large fixed panels of diploid individuals. The cost-effective, open-source nature of our methodology may make it particularly attractive to those working in nonmodel systems.
Biological activities of components of essential oils to alveolar epithelial cells
Authors: Yasuo Takano, Masako Takeda, Yuuya Hinode
Journal: European Respiratory Journal (2013)

Background : It is well known that essential oils of plants have stress palliation, diet and immunostimulation effects. However, little is known about the biological effects of essential oils on respiratory epithelial cells.  Objectives : To evaluate the biological effects of essential oils on respiratory epithelial cells, we have examined cytotoxic, apoptotic and antioxidant activity in components of essential oils using a primary culture of alveolar type II cells  in vitro . Our final goal is to examine applications of these potent essential oil components to respiratory health.  Method : Alveolar type II cells were isolated from Fisher 344 male rats using elastase inserted into the trachea. The cells were exposed to components of essential oils with and without induced oxidative stress by the addition of H 2 O 2  in the presence of Fe 2+  ion for 6 hrs. At the end of the experiment, lactate dehydrogenase (LDH) activity released into the culture medium was determined to reflect the cytotoxic and antioxidant activities.  Results : Cytotoxic activity for geraniol, linalool, mentol, cedrol, nerolidol and borneol were increased dose-dependently up to a concentration of 300 ppm. Eugenol and isoeugenol exerted potent free radical scavenging activities.  Conclusions : The results indicate that components of essential oils produce various biological activities in alveolar type II cells. Eugenol and its compound can be useful protective agents for oxidative respiratory disorder in alveolar regions.
Hypomagnesemia and Inflammation: Clinical and Basic Aspects
Authors: William B. Weglicki
Journal: Annual Review of Nutrition (2012)

In recent years, increasing awareness of hypomagnesemia has resulted in clinical trials that associate this mineral deficiency with diabetes, metabolic syndrome, and drug therapies for cancer and cardiovascular diseases. However, diagnostic testing for tissue deficiency of magnesium still presents a challenge. Investigations of animal and cellular responses to magnesium deficiency have found evidence of complex proinflammatory pathways that may lead to greater understanding of mediators of the pathobiology in neuronal, cardiovascular, intestinal, renal, and hematological tissues. The roles of free radicals, cytokines, neuropeptides, endotoxin, endogenous antioxidants, and vascular permeability, and interventions to limit the inflammatory response associated with these parameters, are outlined in basic studies of magnesium deficiency. It is hoped that this limited review of inflammation associated with some diseases complicated by magnesium deficiency will prompt greater awareness by clinicians and other health providers and in turn increase efforts to prevent and treat this disorder.
Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning?
Authors: H Kusuoka, Y Koretsune, V P Chacko, M L Weisfeldt, E Marban
Journal: Circulation Research (1990)

To elucidate the mechanism of contractile dysfunction in postischemic ("stunned") myocardium, time-resolved measurements of intracellular free Ca2+ concentration ([Ca2+]i) were made using gated 19F nuclear magnetic resonance in seven perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5F-BAPTA. Left ventricular developed pressure decreased to 65 +/- 3% (mean +/- SEM) of control after 15 minutes of global ischemia at 37 degrees C. In stunned myocardium, diastolic [Ca2+]i (0.24 +/- 0.03 microM) was not changed from control (0.18 +/- 0.03 microM, p greater than 0.10), but peak [Ca2+]i (1.03 +/- 0.13 microM) was paradoxically higher than that in control (0.61 +/- 0.06 microM, p less than 0.02). The slope of the relation between developed pressure and Ca2+ transient amplitude in stunned myocardium was significantly lower than that in control (p less than 0.05), even after normalization by maximal Ca2(+)-activated pressure. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to the previously identified decrease in maximal Ca2(+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The increase in the amplitude of Ca2+ transients would require that more ATP be spent in Ca2+ sequestration; thus, decreased efficiency of energy utilization in stunned myocardium would result.
Anatomical correlates of blepharospasm
Authors: Silvina G Horovitz, Anastasia Ford, Muslimah Ali Najee-ullah, John L Ostuni, Mark Hallett
Journal: Translational Neurodegeneration (2012)

Focal dystonia is a neurological disorder characterized by unwanted muscle spasms. Blepharospasm is a focal dystonia producing an involuntary closure of the eyelid. Its etiology is unknown. To investigate if there are structural changes in the white and grey matter of blepharospasm patients, and if the changes are related to disease features. T1 and diffusion-weighted magnetic resonance imaging scans were collected from 14 female blepharospasm patients and 14 healthy matched controls. Grey matter volumes, fractional anisotropy (FA), and mean diffusivity maps were compared between the groups. Based on grey matter differences within the facial portion of the primary motor cortex, the corticobulbar tract was traced and compared between groups. Changes in grey matter in patients included the facial portion of the sensorimotor area and anterior cingulate gyrus. These changes did not correlate with disease duration. Corticobulbar tract volume and peak tract connectivity were decreased in patients compared with controls. There were no significant differences in FA or mean diffusivity between groups. Grey matter changes within the primary sensorimotor and the anterior cingulate cortices in blepharospasm patients may help explain involuntary eyelid closure and the abnormal sensations often reported in this condition.
Prognostic significance of bcl-xL gene expression and apoptotic cell counts in follicular lymphoma
Authors: Wei-Li Zhao, Marjan Ertault Daneshpouy, Nicolas Mounier, Josette Brière, Christophe Leboeuf, Louis-François Plassa, Elisabeth Turpin, Jean-Michel Cayuela, Jean-Claude Ameisen, Christian Gisselbrecht, Anne Janin
Journal: Blood (2003)
Peroxisome proliferator-activated receptor-γ protects against hepatic ischemia/reperfusion injury in mice
Authors: Satoshi Kuboki, Thomas Shin, Nadine Huber, Thorsten Eismann, Elizabeth Galloway, Rebecca Schuster, John Blanchard, Basilia Zingarelli, Alex B. Lentsch
Journal: Hepatology (2007)

The function of peroxisome proliferator-activated receptor-γ (PPARγ) in hepatic inflammation and injury is unclear. In this study, we sought to determine the role of PPARγ in hepatic ischemia/reperfusion injury in mice. Male mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. PPARγ was found to be constitutively activated in hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic PPARγ activation rapidly decreased and remained suppressed throughout the 8-hour reperfusion period. This reduced activation was not a result of decreased protein availability as hepatic nuclear PPARγ, retinoid X receptor-α (RXRα), and PPARγ/RXRα heterodimer expression was maintained. Accompanying the decrease in PPARγ activation was a decrease in the expression of the natural ligand 15-deoxy-Delta12,14-prostaglandin J2. This was associated with reduced interaction of PPARγ and the coactivator, p300. To determine whether PPARγ activation is hepatoprotective during hepatic ischemia/reperfusion injury, mice were treated with the PPARγ agonists, rosiglitazone and connecting peptide. These treatments increased PPARγ activation and reduced liver injury compared to untreated mice. Furthermore, PPARγ-deficient mice had more liver injury after ischemia/reperfusion than their wild-type counterparts. Conclusion: These data suggest that PPARγ is an important endogenous regulator of, and potential therapeutic target for, ischemic liver injury. (Hepatology 2007.)
Lactoferrin protects against acetaminophen-induced liver injury in mice
Authors: Hao Yin, Linling Cheng, Michael Holt, Numsen Hail, Robert MacLaren, Cynthia Ju
Journal: Hepatology (2009)

Acetaminophen-induced liver injury (AILI) is a significant health problem and represents the most frequent cause of drug-induced liver failure in the United States. The development and implementation of successful therapeutic intervention strategies have been demanding, due to significant limitations associated with the current treatment for AILI. Lactoferrin (Lac), a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Our study demonstrated a profound protective effect of Lac in a murine model of AILI, which was not dependent on its iron-binding ability, inhibition of acetaminophen (APAP) metabolism, or a direct cytoprotective effect on hepatocytes. Instead, Lac treatment significantly attenuated APAP-induced liver sinusoidal endothelial cell dysfunction and ameliorated hepatic microcirculation disorder. This protective effect of Lac appeared to be dependent on hepatic resident macrophages (Kupffer cells [KCs]). Conclusion: Collectively, our data indicate that Lac, through activation of KCs, inhibited APAP-induced liver sinusoidal endothelial cell damage and improved hepatic congestion, thereby protecting against AILI. These findings reveal the significant therapeutic potential of Lac during AILI and other types of liver diseases. (Hepatology 2010.)
Histologic and Cell Surface Antigen Studies of Hematopoietic Tumors Induced by Cas-Br-M Murine Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: T N Fredrickson, W Y Langdon, P M Hoffman, J W Hartley, H C Morse
Journal: JNCI Journal of the National Cancer Institute (1984)

Cas-Br-M, a cloned ecotropic murine leukemia virus (MuLV) of wild mouse origin that induces both neurogenic hindlimb paralysis and lymphomas, was injected into NFS/N inbred mice neonatally. Then the mice were observed for the development of neurologic disease and tumors. All mice manifested neurologic abnormalities by 6 months of age, and 58% of the animals died with hematopoietic neoplasms. The tumors included T- and B-cell lymphomas, lymphoblastic lymphoma, erythroleukemias, myelogenous leukemias, and a megakaryocytic leukemia. Cas-Br-M thus appeared to be unique among ecotropic MuLV in inducing a wide spectrum of hematopoietic tumors.
Plasma tissue factor antigen levels in capillary whole blood and venous blood: Effect of tissue factor on prothrombin time
Authors: Emmanuel T. Quien, Enid Morales, Laura A. Cisar, Hugh C. Kim, Catherine Cimini, Parvin Saidi, Claire S. Philipp
Journal: American Journal of Hematology (1997)

To measure the amount of tissue factor released during specimen collection and its potential effect of shortening the prothrombin time, we measured tissue factor and prothrombin time in twenty-three paired venous and capillary blood samples from anticoagulated patients and in ten paired samples from controls. We also compared venous prothrombin time determined by a plasma-based assay with venous and capillary prothrombin time determined with a whole blood assay. Venous specimens were obtained using a two-syringe technique; capillary specimens were obtained by fingerstick after wiping the first drop of blood. Plasma tissue factor was determined by an enzyme-linked immunoabsorbant assay. The patients' mean venous tissue factor (235 +/- 101 pg/ml) and capillary tissue factor (268 +/- 106 pg/ml) were higher than those of the controls (161 +/- 42 pg/ml and 187 +/- 63 pg/ml, respectively, P < 0.05). These differences disappeared after adjusting for age. Capillary tissue factor levels were higher than venous tissue factor (244 +/- 102 pg/ml vs. 213 +/- 93 pg/ml), with a mean difference of 31 pg/ml (P = 0.0001). In addition, whole blood prothrombin time was lower in the capillary than in the venous samples (17.7 +/- 5 sec vs. 18.3 +/- 5.4 sec, P = 0.004). However, there was no correlation between capillary-venous differences in tissue factor and capillary-venous differences in the whole blood prothrombin time. Whole blood capillary and venous prothrombin times highly correlated with the plasma-based venous prothrombin time (r = 0.98, P < 0.0001). These results demonstrate that obtaining blood by fingerstick does not result in a clinically significant release of tissue factor. In addition, we did not observe any interference of plasma tissue factor with the whole blood prothrombin time assay. A direct relationship between tissue factor and age was observed.
Longitudinal Monitoring of Stem Cell Grafts <i>In Vivo</i> Using Magnetic Resonance Imaging with Inducible Maga as a Genetic Reporter
Authors: In K. Cho, Sean P. Moran, Ramesh Paudyal, Karolina Piotrowska-Nitsche, Pei-Hsun Cheng, Xiaodong Zhang, Hui Mao, Anthony W.S. Chan
Journal: Theranostics (2014)

Purpose:The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine.Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts in vivo.Methods: MagA, a bacterial gene involved in the formation of iron oxide nanocrystals, was genetically modified for in vivo monitoring of cell grafts by MRI.Inducible expression of MagA was regulated by a Tet-On (Tet) switch.A mouse embryonic stem cell-line carrying Tet-MagA (mESC-MagA) was established by lentivirus transduction.The impact of expressing MagA in mESCs was evaluated via proliferation assay, cytotoxicity assay, teratoma formation, MRI, and inductively coupled plasma atomic emission spectroscopy (ICP-OES).Mice were grafted with mESCs with and without MagA (mESC-MagA and mESC-WT).The condition of cell grafts with induced "ON" and non-induced "OFF" expression of MagA was longitudinally monitored in vivo using a 7T MRI scanner.After imaging, whole brain samples were harvested for histological assessment.Results: Expression of MagA in mESCs resulted in significant changes in the transverse relaxation rate (R 2 or 1/T 2 ) and susceptibility weighted MRI contrast.The pluripotency of mESCs carrying MagA was not affected in vitro or in vivo.Intracranial mESC-MagA grafts generated sufficient T 2 and susceptibility weighted contrast at 7T.The mESC-MagA grafts can be monitored by MRI longitudinally upon induced expression of MagA by administering doxycycline (Dox) via diet.Conclusion: Our results demonstrate MagA could be used to monitor cell grafts noninvasively, longitudinally, and repetitively, enabling the assessment of cell graft conditions in vivo.
Prevalence of chronic obstructive pulmonary disease and associated risk factors in Uganda (FRESH AIR Uganda): a prospective cross-sectional observational study
Authors: Frederik van Gemert, Bruce Kirenga, Niels Chavannes, Moses Kamya, Simon Luzige, Patrick Musinguzi, John Turyagaruka, Rupert Jones, Ioanna Tsiligianni, Sian Williams, Corina de Jong, Thys van der Molen
Journal: The Lancet Global Health (2014)
Long term vascular complications of Coxiella burnetii infection in Switzerland: cohort study
Authors: P.-Y. Lovey, A. Morabia, D Bleed, O Peter, G Dupuis, J Petite
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the range of long term vascular manifestations of <i>Coxiella burnetii</i> infection. <b>Design:</b> Cohort study in Switzerland of people affected in 1983 by the largest reported outbreak of Q fever and who were followed up 12 years later. Follow up information about possible vascular disease and endocarditis was obtained through a mailed questionnaire and death certificates. <b>Setting:</b> Val de Bagnes, a rural Alpine valley in Switzerland. <b>Participants:</b> 2044 (87%) of 2355 people who had serum testing for <i>Coxiella burnetii</i> infection in 1983: 1247 were classed as not having been infected, 411 were classed as having been acutely infected, and 386 were classed as having been infected before 1983. <b>Main outcome measures:</b> Relative risk controlled for age and sex and 12 year risk of vascular diseases and endocarditis among infected participants as compared with those who had never been infected. <b>Results:</b> The 12 year risk of endocarditis or venous thromboembolic disease was not increased among those who had been acutely infected The 12 year risk of arterial disease was significantly higher among those who had been acutely infected (7%) as compared with those who had never been infected (4%) (relative risk 2.2, 95% confidence interval 1.4 to 3.6). Specifically, there was an increased risk of developing a cerebrovascular accident (relative risk 3.7, 1.6 to 8.4) and cardiac ischaemia (relative risk 1.9, 1.04 to 3.4). 12 year mortality was significantly higher among the 411 people who had been acutely infected in 1983 (9.7%; age adjusted relative risk 1.8, 1.2 to 2.6) when compared with the 1247 participants who had remained serologically negative in 1983 (7.0%). <b>Conclusions:</b><i>Coxiella burnetii</i> infection may cause long term complications including vascular disease. <h3>Key messages</h3> The risk of developing venous or arterial disease after infection with <i>Coxiella burnetii</i> was assessed in a Swiss cohort of 2044 people exposed to the largest reported outbreak of Q fever Twelve year mortality was significantly higher among people who had been acutely infected in 1983 The 12 year risk of arterial disease was significantly higher among those who had been acutely infected (7%) than among those who had not been infected (4%) Compared with those participants who tested negative, those who were acutely infected with <i>C burnetii</i> had an increased relative risk of having a cerebrovascular accident or cardiac ischaemia Infection with <i>C burnetii</i> may be responsible for the development of vascular diseases in addition to infection with <i>Chlamydia pneumoniae</i>, cytomegalovirus, and <i>Helicobacter pylori</i>
A Guide to Care of the Elderly
Authors: A J. Campbell
Journal: BMJ (1996)

Ed R B Shukla, D Brooks HMSO, £40, pp 361 ISBN 0 11 701830 9

Elderly people, says A Guide to Care of the Elderly, “having benefited from the rewards of a consumer society, demand a style of provision and a quality of service far in advance of that provided in former years.”

Any guide to the care of elderly people must cover not only the delivery of services but the social, political, and legal setting within which the services are provided. The difficulty for the clinician providing high quality care is the breadth …
Exercise in pregnancy
Authors: J. A. Jordan
Journal: British Journal of Sports Medicine (1986)

The tackler was aware of severe pain and a doctor was called onto the field.Examination of the injured player revealed a tender bony lump in the lower dorsal spine but no evidence of neurological damage.The injured man was treated as a potential fractured spine, and X-rays taken on arrival at hospital showed an unstable fracture/dislocation of D11 (Fig. 5) requiring internal fixation.I~~~~/ i
Computer simulations of three-dimensional propagation in ventricular myocardium. Effects of intramural fiber rotation and inhomogeneous conductivity on epicardial activation.
Authors: A E Pollard, M J Burgess, K W Spitzer
Journal: Circulation Research (1993)

Three-dimensional membrane-based simulations of action potential propagation in ventricular myocardium were performed. Specifically, the effects of the intramural rotation of the fiber axes and inhomogeneous conductivity on the timing and pattern of epicardial activation were examined. Models were built, with approximately 400,000 microscopic elements arranged in rectangular parallelepipeds in each model. Simulations used the nonlinear Ebihara and Johnson membrane equations for the fast sodium current. Constructed models had histological features of ventricular myocardium. All models were anisotropic. In a subset of the models, an abrupt intramural rotation of the fiber axes was included. This feature was also combined with randomly distributed inhomogeneous conductivity and regions of high transverse resistance to represent nonuniform anisotropy in a further subset of the models. Epicardial stimuli were applied for each simulation. Three-dimensional activation patterns and epicardial isochron maps were constructed from the simulations. We noted that the rotation of fiber axes accelerated epicardial activation distant from the stimulus site. The inhomogeneous conductivity caused regional acceleration and deceleration of activation spread. We also noted features of epicardial activation that resulted from the fiber rotation, and the inhomogeneous conductivity corresponded to that observed in maps from experimental animals.