tbuckley/cabot-search huggingface dataset:
An Ancient Transpecific Polymorphism Shows Extreme Divergence in a Multitrait Cline in an Intertidal Snail (Nucella lapillus (L.))
Authors: Richard R. Kirby
Journal: Molecular Biology and Evolution (2000)

Clines in intraspecific genetic variation are frequently associated with an environmental transition. Here, divergence among nucleotide sequences of two nuclear loci, cytosolic and mitochondrial malate dehydrogenase (cMDH and mMDH, respectively), is described, in a multitrait cline over a distance of ca. 3 km where shell phenotype, allozyme, mitochondrial DNA haplotype, and centric fusion (Robertsonian translocations) frequencies covary with temperature and humidity and change abruptly in a continuous population of the dog-whelk (Nucella lapillus), a common intertidal snail of the north temperate Atlantic. Protein electrophoresis has already shown two alleles of mMDH varying from fixation of one allele to near fixation of the other, whereas cMDH appears to be monomorphic. The results of this study show a striking disparity in nucleotide sequence divergence among alleles at the two loci, with extreme molecular differentiation in one of them. Four alleles of cMDH were found to have nucleotide and amino acid sequence divergences of 0.4% and 0.3%, respectively. In contrast, the two mMDH cDNA alleles differed by 23% and 20% at the nucleotide and amino acid levels, respectively. Analysis of a 91-bp partial nucleotide sequence of mMDH from Nucella freycineti, the closest relative of N. lapillus, revealed two similar alleles and indicated that the divergence in mMDH in N. lapillus represents an ancient transpecific polymorphism in these Nucella. Together with earlier studies on variation in N. lapillus, it is argued that the polymorphism in mMDH and the clines in N. lapillus represent the presence of two persistent coadapted gene complexes, multitrait coevolving genetic solutions to environmental variation, which may presently enable this snail to exploit a diverse environment successfully.
The Cartesian Broadway
Authors: Christopher W. Tyler
Journal: Behavioral and Brain Sciences (1998)

Although Pessoa, Teller &amp; Noë make excellent points concerning the need for a mechanism of filling-in, they throw out the baby of neural specificity with the bathwater of isomorphism and the homuncular observer. The core act of perception is sensory processing by a stationary observer and does not require overt behavioral interaction with the environment. The complexity of intracortical interconnectivity does not preclude local specificity in the representation of higher-order stimulus properties.
Transforming Growth Factor β Receptor Type II Inactivation Promotes the Establishment and Progression of Colon Cancer
Authors: Swati Biswas, Anna Chytil, Kay Washington, Judith Romero-Gallo, Agnieszka E. Gorska, Pamela S. Wirth, Shiva Gautam, Harold L. Moses, William M. Grady
Journal: Cancer Research (2004)

Abstract Deregulation of members of the transforming growth factor (TGF)-β signaling pathway occurs often in colon cancers and is believed to affect the formation of primary colon cancer. Mutational inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway and occurs in ∼20–30% of all colon cancers. By mating Fabpl4xat-132 Cre mice with Tgfbr2flx/flx mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-β signaling in vivo on colon cancer formation induced by azoxymethane (AOM). We have observed a significant increase in the number of AOM-induced adenomas and adenocarcinomas in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice compared with Tgfbr2flx/flx mice, which have intact TGF-β receptor type II (TGFBR2) in the colon epithelium, and we have found increased proliferation in the neoplasms occurring in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice. These results implicate the loss of TGF-β-mediated growth inhibition as one of the in vivo mechanisms through which TGFBR2 inactivation contributes to colon cancer formation. Thus, we have demonstrated that loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms, providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor gene in the colon.
Metabolism of Ischemic Cardiac Muscle
Authors: JOHN P. KALTENBACH, ROBERT B. JENNINGS
Journal: Circulation Research (1960)

The aerobic metabolism of homogenates of normal and ischemic left ventricle was compared in dogs at various time intervals (15 min. to 24 hours) after high ligation of the circumflex branch of the left coronary artery. Glucose and fructose-1,6-diphosphate were used as substrates. The injured tissue was taken from the posterior papillary muscle (PP) and the non-ischemic tissue from the anterior superior septum (LV). Both oxygen consumption and organic phosphorus (Δ organic phosphorus) were slightly decreased in PP at 15 and 30 min. after ligation. Between 30 and 60 min., there was a sharp decrease in oxygen consumption and Δ organic phosphorus falling to 40 to 50 per cent of control values at 60 min. A further decrease was observed at 180 min., and at 24 hours there was a complete loss of oxidative metabolism in the PP. A striking increase in organic phosphorus metabolism and oxygen consumption was observed in the non-ischemic portion of the myocardium 60 and 180 min. after ligation.
Comment on: Hardikar et al. Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia. Diabetes Care 2012;35:797–802
Authors: Roger K. Schindhelm, Margreet Schoorl, Johannes van Pelt
Journal: Diabetes Care (2013)

We read with great interest the article by Hardikar et al. (1). In their epidemiological study in nondiabetic subjects, the authors observed an inverse association between HbA1c and hemoglobin levels, mean cell volume, and mean cell hemoglobin. In the multivariate models, laboratory parameters indicating iron deficiency anemia were negatively associated with HbA1c. On the basis …
Natural killer cell activity of peripheral blood mononuclear cells from patients with various forms of lupus erythematosus
Authors: MARIA BŁASZCZYK, S. MAJEWSKI, MARIA WASIK, T. CHORZELSKI, STEFANIA JABŁONSKA
Journal: British Journal of Dermatology (1987)

Journal Article Natural killer cell activity of peripheral blood mononuclear cells from patients with various forms of lupus erythematosus Get access MARIA BŁASZCZYK, MARIA BŁASZCZYK Department of Dermatology, Warsaw Medical Academy, Warsaw, Poland M. Blaszczyk, M. D., Department of Dermatology, Warsaw Medical Academy, Koszykowa 82A, 02‐008 Warsaw, Poland. Search for other works by this author on: Oxford Academic Google Scholar S. MAJEWSKI, S. MAJEWSKI Department of Dermatology, Warsaw Medical Academy, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar MARIA WASIK, MARIA WASIK Transplantation Institute, Warsaw Medical Academy, Warsaw, PolandDepartment of Dermatology, Warsaw Medical Academy, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar T. CHORZELSKI, T. CHORZELSKI Department of Dermatology, Warsaw Medical Academy, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar STEFANIA JABŁONSKA STEFANIA JABŁONSKA Department of Dermatology, Warsaw Medical Academy, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 6, 1 December 1987, Pages 709–714, https://doi.org/10.1111/j.1365-2133.1987.tb07350.x Published: 01 December 1987
Respiratory symptoms, lung function tests, and sensitization to work-related allergens in female cleaners
Authors: Dragan Mijakoski, Jovanka Karadzinska-Bislimovska, Sasho Stoleski, Jordan Minov, Mimoza Marsenic
Journal: European Respiratory Journal (2013)

Objective. To assess occurrence of respiratory symptoms, lung function impairment, and sensitization to work-related allergens among female cleaners. Methods. We performed a cross-sectional study including 50 female cleaners (mean age 40.3±7.9 years, mean job duration 14.3±8.3 years). In addition, 50 female office workers (mean age 41.9±9.6 years, mean job duration 15.9±7.3 years) were examined as a control. Evaluation of examined subjects included completion of a questionnaire on respiratory symptoms in the last 12 months, lung function testing, histamine challenge test (PC20 ≤ 8 mg/mL), and patch testing to work-related allergens. Results. Compared with office workers, cleaners had more frequently respiratory symptoms (cough, phlegm, wheezing, and shortness of breath) in the last 12 months (36.0% vs. 16.0%, P
Hsp70–Bag3 Interactions Regulate Cancer-Related Signaling Networks
Authors: Teresa A. Colvin, Vladimir L. Gabai, Jianlin Gong, Stuart K. Calderwood, Hu Li, Suryaram Gummuluru, Olga N. Matchuk, Svetlana G. Smirnova, Nina V. Orlova, Irina A. Zamulaeva, Mikel Garcia-Marcos, Xiaokai Li, Z.T. Young, Jennifer N. Rauch, Jason E. Gestwicki, Shinichi Takayama, Michael Y. Sherman
Journal: Cancer Research (2014)

Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here, we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling by modulating the activity of the transcription factors NF-κB, FoxM1, Hif1α, the translation regulator HuR, and the cell-cycle regulators p21 and survivin. We also identified a small-molecule inhibitor, YM-1, that disrupts the Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anticancer target.
THE EFFECT OF DIET ON THE SUSCEPTIBILITY OF THE MOUSE TO PNEUMONIA VIRUS OF MICE (PVM)
Authors: George S. Mirick, William B. Leftwich
Journal: The Journal of Experimental Medicine (1949)

Young mice fed diets deficient in pyridoxine for 8 days or longer before the inoculation of PVM, as well as after inoculation, were more susceptible to infection than control mice fed complete diets. Young mice fed a pyridoxine-deficient diet gained weight as well as controls fed a complete diet for 5 weeks, but they lost weight in the 6th week. The ratio of thymus or spleen weight to body weight was less in mice fed a pyridoxine-deficient diet for 6 weeks than in controls fed a complete diet. Histologically the thymuses and spleens showed hypoplasia. No measurable difference in antibodies against PVM was found in the sera of uninoculated mice fed complete or pyridoxine-deficient diets for 6 weeks.
Thoracoabdominal Calcifications Predict Cardiovascular Disease Mortality in Type 2 Diabetic and Nondiabetic Subjects
Authors: Auni Juutilainen, Seppo Lehto, Matti Suhonen, Tapani Rönnemaa, Markku Laakso
Journal: Diabetes Care (2009)

OBJECTIVE To evaluate cardiovascular disease (CVD) and total mortality associated with thoracoabdominal calcifications. RESEARCH DESIGN AND METHODS Thoracoabdominal calcifications of native radiograms were evaluated in 833 subjects with type 2 diabetes and 1,292 subjects without diabetes, aged 45-64 years, without prior evidence of CVD. The type 2 diabetic and nondiabetic study cohorts were followed up for 18 years. RESULTS After adjustment for conventional risk factors, marked thoracoabdominal calcifications predicted CVD/total mortality with hazard ratio (HR) (95% CI) of 1.5 (0.8-3.0)/1.8 (1.1-2.9) in type 2 diabetic men, 3.0 (1.6-5.7)/3.1 (1.9-5.0) in type 2 diabetic women, 5.0 (2.2-12)/4.0 (2.2-7.4) in nondiabetic men, and 7.8 (1.8-34)/3.0 (1.3-7.0) in nondiabetic women and in the presence of C-reactive protein below/over 3 mg/l with HR of 2.4 (1.3-4.4)/3.0 (1.4-6.1) in type 2 diabetic subjects and 4.0 (1.5-10.8)/6.6 (2.7-16.0) in nondiabetic subjects. CONCLUSIONS Thoracoabdominal calcifications in native radiograms are significant predictors of CVD and total mortality, especially in type 2 diabetic and nondiabetic women with elevated high-sensitivity C-reactive protein level.
Prevalence of War-Related Mental Health Conditions and Association With Displacement Status in Postwar Jaffna District, Sri Lanka
Authors: Farah Husain, Mark Anderson, Barbara Lopes Cardozo, Kristin Becknell, Curtis Blanton, Diane Araki, Eeshara Kottegoda Vithana
Journal: JAMA (2011)

Nearly 2.7 million individuals worldwide are internally displaced (seeking refuge in secure areas of their own country) annually by armed conflict. Although the psychological impact of war has been well documented, less is known about the mental health symptoms of forced displacement among internally displaced persons.To estimate the prevalence of the most common war-related mental health conditions, symptoms of posttraumatic stress disorder (PTSD), anxiety, and depression, and to assess the association between displacement status and these conditions in postwar Jaffna District, Sri Lanka.Between July and September 2009, a cross-sectional multistage cluster sample survey was conducted among 1517 Jaffna District households including 2 internally displaced persons camps. The response rate was 92% (1448 respondents, 1409 eligible respondents). Two percent of participants (n = 80) were currently displaced, 29.5% (n = 539) were recently resettled, and 68.5% (n = 790) were long-term residents. Bivariable analyses followed by multivariable logistic regression models were performed to determine the association between displacement status and mental health.Symptom criteria of PTSD, anxiety, and depression as measured by the Harvard Trauma Questionnaire and the Hopkins Symptom Checklist-25.The overall prevalences of symptoms of PTSD, anxiety, and depression were 7.0% (95% confidence interval [CI], 5.1%-9.7%), 32.6% (95% CI, 28.5%-36.9%), and 22.2% (95% CI, 18.2%-26.5%), respectively. Currently displaced participants were more likely to report symptoms of PTSD (odds ratio [OR], 2.71; 95% CI, 1.28-5.73), anxiety (OR, 2.91; 95% CI, 1.89-4.48), and depression (OR, 4.55; 95% CI, 2.47-8.39) compared with long-term residents. Recently resettled residents were more likely to report symptoms of PTSD (OR, 1.96; 95% CI, 1.11-3.47) compared with long-term residents. However, displacement was no longer associated with mental health symptoms after controlling for trauma exposure.Among residents of Jaffna District in Sri Lanka, prevalence of symptoms of war-related mental health conditions was substantial and significantly associated with displacement status and underlying trauma exposure.
Prognostic Significance of Molecular Remission in Follicular Lymphoma
Authors: Ulrich Dührsen, Andreas Hüttmann, Jan Dürig
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: In their report on patients with relapsed or refractory follicular lymphoma, van Oers et al come to the conclusion that the presence of tumor cells in blood or bone marrow detected at the end of induction therapy by BCL2/IgH major break point region (MBR) polymerase chain reaction (PCR) is not predictive of progression-free survival. This conclusion is at variance with previous publications cited by the authors. The results may be a result of an inappropriate selection of patients rather than a genuine inability of BCL2/IgH PCR to predict outcome. Follicular lymphoma is a heterogeneous disorder. In Western countries, only approximately 70% to 90% of patients harbor the t(14;18) translocation juxtaposing BCL2 and IgH. In patients carrying the translocation, up to 50% have a break point outside the MBR of the BCL2 gene. Van Oers et al included all patients with follicular lymphoma regardless of t(14;18) status in their investigation, and they limited the PCR analysis to the MBR. Applying the distribution of genetic abnormalities to the trial cohort, the lymphoma cells of half the patients may not have been detectable by the approach chosen. This may explain why the proportion of patients with proven blood or bone marrow involvement was lower than expected and molecular evidence of marrow involvement did not correlate with histologic evidence. Although the presence or absence of lymphoma cells lacking the BCL2/IgH MBR fusion could not be evaluated, these patients were included in the group of patients without evidence of blood and marrow involvement. Thus, although the BCL2/IgH MBR–positive group was homogeneous with regard to the presence of tumor cells, the BCL2/IgH MBR–negative group was heterogeneous because, in addition to patients with an MBR fusion and no evidence of blood and marrow involvement, it also included an unknown number of patients whose status escaped detectability. It seems reasonable to assume that a substantial proportion of these latter patients also had residual tumor cells in blood and bone marrow. The conclusions drawn by van Oers et al would have been appropriate had they limited their analysis to lymphomas with proven BCL2/IgH MBR fusion. Instead, they analyzed all lymphomas irrespective of their molecular makeup and regarded failure to obtain a PCR product as evidence of absence of tumor cells. This conclusion, however, is illegitimate unless the tumor cells are known to harbor the genetic marker targeted by the PCR primers. Therefore, the investigations by van Oers et al are not suited to challenge the existing literature on the prognostic significance of molecular remission in follicular lymphoma. Whether maintenance therapy with rituximab is equally beneficial in patients with or without molecular remission remains unresolved.
Distribution of GPR30, a Seven Membrane–Spanning Estrogen Receptor, in Primary Breast Cancer and its Association with Clinicopathologic Determinants of Tumor Progression
Authors: Edward J. Filardo, Carl T. Graeber, Jeffrey A. Quinn, Murray B. Resnick, Dilip Giri, Ronald A. DeLellis, Margaret M. Steinhoff, Edmond Sabo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparan-bound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables. Experimental Design: Immunohistochemical analysis of a National Cancer Institute–sponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis. Results: GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER−GPR30−) in 19% (61 of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P &amp;lt; 0.05). The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P = 0.014; odds ratio, 1.9). Conclusions: GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.
Loss of p53 Accelerates Neointimal Lesions of Vein Bypass Grafts in Mice
Authors: Ursula Mayr, Manuel Mayr, Chaohong Li, Florian Wernig, Hermann Dietrich, Yanhua Hu, Qingbo Xu
Journal: Circulation Research (2002)

The transcription factor p53 is essentially involved in regulation of cell death and proliferation. Recently, we have established a mouse model for vein graft arteriosclerosis by grafting autologous jugular veins or vena cava to carotid arteries. Using this model, we studied the role of p53 in the development of vein graft arteriosclerosis in p53 −/− mice. Four weeks after grafting, neointimal hyperplasia of vein grafts in p53 −/− mice was increased 2-fold compared with that of wild-type controls. Cell component analysis revealed that neointimal lesions in p53 −/− mice consisted mainly of α-actin positive smooth muscle cells (SMCs), whereas the majority of cells in wild-type mice were MAC-1 (CD11b/18)-positive at 4 weeks. Importantly, SMC apoptosis as determined by TUNEL assay was significantly reduced in p53 −/− vein grafts. TUNEL positive cells in wild-type vein grafts markedly increased from 0.5% to 6.4% of total cells 4 weeks postoperatively, but remained virtually unchanged in p53 −/− grafts (0.8%). Immunofluorescence analysis revealed that increased p53 expression in neointimal SMCs of wild-type, but not p53 −/− , mice coincided with oxidative DNA damage in vein grafts. Interestingly, SMCs of p53 −/− mice showed increased apoptosis in response to TNFα and decreased apoptosis in response to sodium nitroprusside. Additionally, p53-deficient SMCs showed a higher rate of proliferation and migration and expressed higher levels of matrix metalloproteinases. Thus, p53 deficiency accelerates neointima formation by facilitating SMC proliferation as well as abrogating cell apoptosis.
Detection of Atherosclerotic Plaque With Gadofluorine-Enhanced Magnetic Resonance Imaging
Authors: Jörg Barkhausen, Wolfgang Ebert, Claudia Heyer, Jörg F. Debatin, Hanns-Joachim Weinmann
Journal: Circulation (2003)

The purpose of this study was to visualize atherosclerotic plaques independently of luminal narrowing using T1-weighted contrast-enhanced MRI.Eight Watanabe heritable hyperlipidemic (WHHL) rabbits, aged 9 to 18 months, and 8 age-matched controls (New Zealand White rabbits) underwent MRI of the aortic arch before and up to 48 hours after injection of 100 micromol/kg Gadofluorine (Schering AG). Additionally, 8 WHHL rabbits were examined with Magnevist (Schering AG). A half-Fourier acquisition single-shot turbo-spin-echo (HASTE) sequence and a T1-weighted inversion-recovery turbo fast, low-angle shot sequence were used for data acquisition. Immediately after the MR examination, the animals were killed, the aorta was stained with Sudan red, and ex vivo imaging of the stained aortic specimens was performed. Additionally, gadolinium concentrations in plaque (Sudan-positive) and normal (Sudan-negative) aortic wall segments were measured. Plain MR imaging revealed no plaques in the aortic arch in either animal group. Enhancement occurred in the aortic wall of all WHHL rabbits examined with Gadofluorine but not in the vessel wall of animals examined with Magnevist and the control group. Sudan red staining demonstrated multiple plaques in the aortic arch of all WHHL rabbits. Ex vivo imaging demonstrated that the area of hyperenhancement matched the area of plaques stained with Sudan red. The gadolinium concentration was 7+/-5 nmol/g for normal aortic wall of the control group and 368+/-30 nmol/g for aortic wall with plaque in WHHL.Gadofluorine enhances the imaging of atherosclerotic plaques and enables improved plaque detection of even nonstenotic lesions that are not visible on unenhanced MRI.