tbuckley/cabot-search huggingface dataset:
Molecular Evolution of FLORICAULA/LEAFY Orthologs in the Andropogoneae (Poaceae)
Authors: Kirsten Bomblies, John F. Doebley
Journal: Molecular Biology and Evolution (2005)

Members of the grass family (Poaceae) exhibit a broad range of inflorescence structures and other morphologies, making the grasses an interesting model system for studying the evolution of development. Here we present an analysis of the molecular evolution of FLORICAULA/LEAFY-like genes, which are important developmental regulatory loci known to affect inflorescence development in a wide range of flowering plant species. We have focused on sequences from the Andropogoneae, a tribe within the grass family that includes maize (Zea mays ssp. mays) and Sorghum (Sorghum bicolor). The FLORICAULA/LEAFY gene phylogeny we generated largely agrees with previously published phylogenies for the Andropogoneae using other nuclear genes but is unique in that it includes both members of one of the many duplicate gene sets present in maize. The placement of these sequences in the phylogeny suggests that the duplication of the maize FLORICAULA/LEAFY orthologs, zfl1 and zfl2, is a consequence of a proposed tetraploidy event that occurred in the common ancestor of Zea and a closely related genus, Tripsacum. Our data are consistent with the hypothesis that the transcribed regions of the FLORICAULA/LEAFY-like genes in the Andropogoneae are functionally constrained at both nonsynonymous and synonymous sites and show no evidence of directional selection. We also examined conservation of short noncoding sequences in the first intron, which may play a role in gene regulation. Finally, we investigated the genetic diversity of one of the two maize FLORICAULA/LEAFY orthologs, zfl2, in maize and its wild ancestor, teosinte (Z. mays ssp. parviglumis), and found no evidence for selection pressure resulting from maize domestication within the zfl2-coding region.
The value of genotypic analysis in the assessment of cutaneous plasmacytomas
Authors: T. MIYAMOTO, T. KOBAYASHI, Y. HAGARI, M. MIHARA
Journal: British Journal of Dermatology (1997)

We report a 79-year-old woman with primary cutaneous plasmacytoma in whom polymerase chain reaction (PCR) was used to demonstrate the monoclonality of the tumour. Four years after presentation, further skin lesions occurred and PCR again showed evidence of monoclonality despite the histology being non-specific. The reported frequency of multiple primary cutaneous plasmacytoma is increasing, and the mortality rate of patients with multiple lesions is three times that of those with a solitary lesion. PCR may be a useful technique for assessing such patients at presentation.
Thorax update: October 2007–September 2008
Authors: Jadwiga A Wedzicha, Sebastian L Johnston
Journal: Thorax (2008)

We have now completed our sixth year as Thorax editors and are delighted that the Journal has continued to be so successful. As usual, the annual round of impact factor announcements was eagerly awaited by the editorial team and we were all delighted with the news that our impact factor for 2007, published in June 2008, had risen to the highest ever for Thorax at 6.226. The impact factor for 2007 reflects the number of citations in 2007 divided by the number of original papers and reviews published in Thorax in 2005 and 2006. We have thus maintained our position as the second highest ranked respiratory journal in terms of impact factor, behind the American Journal of Respiratory and Critical Care Medicine . This increase in the Thorax impact factor is a result of the high quality papers and reviews that you have all submitted to the journal for publication.

Perhaps the most visible change has been (we hope!) the change of front cover and our successful introduction of images to illustrate each issue (figs 1–3). These images were selected by the COPD research team at UCL Medical School, according to some democratic process! As they have to be of high quality, they come from the Science Photo Library. In addition, the inside page format has changed, and this is consistent with the new house style of BMJ Journals.



Figure 1  Thorax cover.



Figure 2  Thorax cover.



Figure 3  Thorax cover.

The number of submissions over the past year has remained steady compared with previous years at 1434, with 872 full original papers submitted to the journal. The time to the first decision on an original paper …
Infection of Endothelium With E1 <sup>−</sup> E4 <sup>+</sup> , but Not E1 <sup>−</sup> E4 <sup>−</sup> , Adenovirus Gene Transfer Vectors Enhances Leukocyte Adhesion and Migration by Modulation of ICAM-1, VCAM-1, CD34, and Chemokine Expression
Authors: Shahin Rafii, Sergio Dias, Sarah Meeus, Koichi Hattori, Ramalingam Ramachandran, Fred Feuerback, Stefan Worgall, Neil R. Hackett, Ronald G. Crystal
Journal: Circulation Research (2001)

Abstract —Intravascular introduction of replication-deficient adenoviral vectors (Advectors) provides an ideal model of delivery of transgenes for the treatment of various vascular abnormalities. On the basis of the knowledge that Advectors can induce inflammatory responses after intravascular administration, we speculated that cellular activation by Advector infection could directly modulate the endothelial cell (EC) adhesion molecule/chemokine expression repertoire. Infection of human umbilical vein ECs or bone marrow microvascular ECs with an E1 − E4 + Advector resulted in the upregulation of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD34, but not E-selectin, P-selectin, CD36, CD13, CD44, HLA-DR or PECAM. Upregulation of ICAM-1, VCAM-1, and CD34 was apparent 12 hours after infection and persisted for weeks after infection. Selective induction of adhesion molecules was mediated by the presence of the E4 gene in the Advector, because infection of ECs with an E1 − E4 − Advector had no effect on adhesion molecule expression. ECs infected with E1 − E4 + Advector, but not those infected with E1 − E4 − Advector, supported the adhesion of leukocytes. Monoclonal antibodies to ICAM-1 and VCAM-1 inhibited adhesion of leukocytes to E1 − E4 + -infected ECs. Infection of the ECs with E1 − E4 + Advector, but not E1 − E4 − Advector, resulted in downregulation of expression of chemocytokines, including interleukin-8, MCP-1, RANTES, and GM-CSF. Nonetheless, a large number of leukocytes migrated through ECs infected with E1 − E4 + , but not those infected with E1 − E4 l− , in response to exogenous chemokines. These results demonstrate that infection of ECs with E1 − E4 + Advectors, but not E1 − E4 − Advectors, may directly augment inflammatory responses by upregulating expression of adhesion molecules and enhancing migration through Advector-infected ECs and suggest that E1 − E4 − Advectors may be a better choice for gene-transfer strategies directed to the ECs.
Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions
Authors: Marc Damelin, Alexander Bankovich, Albert Park, Jorge Aguilar, Wade Anderson, Marianne Santaguida, Monette Aujay, Sarah Fong, Kiran Khandke, Virginia Pulito, Elana Ernstoff, Paul Escarpe, Jeffrey Bernstein, Marybeth Pysz, Wenyan Zhong, Erik Upeslacis, Judy Lucas, Justin Lucas, Timothy Nichols, Kathryn Loving, Orit Foord, Johannes Hampl, Robert Stull, Frank Barletta, Hadi Falahatpisheh, Puja Sapra, Hans-Peter Gerber, Scott J. Dylla
Journal: Clinical Cancer Research (2015)

Triple-negative breast cancer (TNBC) and ovarian cancer each comprise heterogeneous tumors, for which current therapies have little clinical benefit. Novel therapies that target and eradicate tumor-initiating cells (TIC) are needed to significantly improve survival.A panel of well-annotated patient-derived xenografts (PDX) was established, and surface markers that enriched for TIC in specific tumor subtypes were empirically determined. The TICs were queried for overexpressed antigens, one of which was selected to be the target of an antibody-drug conjugate (ADC). The efficacy of the ADC was evaluated in 15 PDX models to generate hypotheses for patient stratification.We herein identified E-cadherin (CD324) as a surface antigen able to reproducibly enrich for TIC in well-annotated, low-passage TNBC and ovarian cancer PDXs. Gene expression analysis of TIC led to the identification of Ephrin-A4 (EFNA4) as a prospective therapeutic target. An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin achieved sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo. Non-claudin low TNBC tumors exhibited higher expression and more robust responses than other breast cancer subtypes, suggesting a specific translational application for tumor subclassification.These findings demonstrate the potential of PF-06647263 (anti-EFNA4-ADC) as a first-in-class compound designed to eradicate TIC. The use of well-annotated PDX for drug discovery enabled the identification of a novel TIC target, pharmacologic evaluation of the compound, and translational studies to inform clinical development.
C3a Mediates Epithelial-to-Mesenchymal Transition in Proteinuric Nephropathy
Authors: Ziyong Tang, Bao Lu, Ellen Hatch, Steven H. Sacks, Neil S. Sheerin
Journal: Journal of the American Society of Nephrology (2009)

Tubulointerstitial inflammation and progressive fibrosis are common pathways that lead to kidney failure in proteinuric nephropathies. Activation of the complement system has been implicated in the development of tubulointerstitial injury in clinical and animal studies, but the mechanism by which complement induces kidney injury is not fully understood. Here, we studied the effect of complement on the phenotype of tubular epithelial cells. Tubular epithelial cells exposed to serum proteins adopted phenotypic and functional characteristics of mesenchymal cells. Expression of E-cadherin protein decreased and expression of both alpha-smooth muscle actin protein and collagen I mRNA increased. Exposure of the cells to the complement anaphylotoxin C3a induced similar features. Treating with a C3a receptor (C3aR) antagonist prevented both C3a- and serum-induced epithelial-to-mesenchymal transition. In the adriamycin-induced proteinuria model, C3aR-deficient mice demonstrated less injury, preserved renal function, and improved survival compared with wild-type mice. Furthermore, the kidneys of C3aR-deficient mice had significantly less interstitial collagen I and alpha-smooth muscle actin. In summary, the complement anaphylotoxin C3a is an important mediator of glomerular and tubulointerstitial injury and can induce tubular epithelial-to-mesenchymal transition.
Preventing Bone Loss in Renal Transplant Recipients with Vitamin D
Authors: Amgad E. El-Agroudy, Amr A. El-Husseini, Moharam El-Sayed, Mohamed A. Ghoneim
Journal: Journal of the American Society of Nephrology (2003)

Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated.
Akt/GSK3 Signaling in the Action of Psychotropic Drugs
Authors: Jean-Martin Beaulieu, Raul R. Gainetdinov, Marc G. Caron
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Psychotropic drugs acting on monoamine neurotransmission are major pharmacological treatments for neuropsychiatric conditions such as schizophrenia, depression, bipolar disorder, Tourette syndrome, ADHD, and Alzheimer disease. Independent lines of research involving biochemical and behavioral approaches in normal and/or genetically modified mice provide converging evidence for an involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by dopamine and serotonin (5-HT). These signaling molecules have also received attention for their role in the actions of psychoactive drugs such as antidepressants, antipsychotics, lithium, and other mood stabilizers. Furthermore, investigations of the mechanism by which D2 dopamine receptors regulate Akt/GSK3 signaling strongly support the physiological relevance of a new modality of G protein-coupled receptor (GPCR) signaling involving the multifunctional scaffolding protein beta-arrestin 2. Elucidation of the contribution of multiple signaling pathways to the action of psychotropic drugs may provide a better biological understanding of psychiatric disorders and lead to more efficient therapeutics.
Progressive reduction in norepinephrine overflow during cardiac sympathetic nerve stimulation in the anaesthetized dog
Authors: M. N. LEVY, B. BLATTBERG
Journal: Cardiovascular Research (1976)

The left ansa subclavia was stimulated at supramaximal intensity at a frequency of 8 Hz in open-chest, anaesthetized dogs for periods of about 10 min. Arterial blood pressure, myocardial contractile force, and coronary sinus blood flow reached peak values after 1 or 2 min of stimulation, and then declined gradually throughout the remainder of stimulation. In hearts that averaged 159± 10 (SEM) g, the norepinephrine (NE) overflow rose to a peak value of 470 ±128 ng/min at the end of 1 min of sympathetic stimulation in the control animals. By the 10th min of stimulation, the NE overflow had diminished to 97±24 ng/min. In animals pretreated with cocaine (5 mg/kg) or with phenoxybenzamine (5 mg/kg), the peak NE overflow rates were 288 ±62 and 980±148 mg/min, respectively, and the rate of NE overflow declined to levels of 104 ± 39 and 128±30 ng/min, respectively, by the 10th min of stimulation. Since there was a profound, progressive diminution in the rate of NE overflow during sustained cardiac sympathetic stimulation regardless of whether or not NE reuptake was suppressed, it is concluded that the reduction in NE overflow reflects a curtailment of neuronal release of NE rather than an acceleration of reuptake.
Folate and Risk of Breast Cancer: A Meta-analysis
Authors: Susanna C Larsson, Edward Giovannucci, Alicja Wolk
Journal: JNCI Journal of the National Cancer Institute (2007)

Epidemiologic findings are inconsistent concerning risk for breast cancer associated with low folate intake or blood folate levels. We performed a meta-analysis of prospective and case-control studies to examine folate intake and levels in relation to risk of breast cancer.We searched MEDLINE for studies of this association that were published in any language from January 1, 1966, through November 1, 2006. Study-specific risk estimates were pooled by use of a random-effects model. All statistical tests were two-sided.Folate intake in increments of 200 microg/day was not associated with the risk of breast cancer in prospective studies (estimated summary relative risk [RR] = 0.97, 95% confidence interval [CI] = 0.88 to 1.07, for dietary folate [eight studies; 302,959 participants and 8367 patients with breast cancer], and RR = 1.01, 95% CI = 0.97 to 1.05, for total folate [six studies; 306,209 participants and 8165 patients with breast cancer]) but was statistically significantly inversely associated with risk in case-control studies (estimated summary odds ratio [OR] = 0.80, 95% CI = 0.72 to 0.89, for dietary folate [13 studies; 8558 case patients and 10,812 control subjects], and OR = 0.93, 95% CI = 0.81 to 1.07, for total folate [three studies; 2184 case patients and 3233 control subjects]). High blood folate levels versus low levels were not statistically significantly associated with the risk of breast cancer in prospective studies (OR = 0.81, 95% CI = 0.59 to 1.10 [three studies]) or in case-control studies (OR = 0.41, 95% CI = 0.15 to 1.10 [two studies]). Among the two prospective studies and two case-control studies that stratified by alcohol consumption, high folate intake (comparing the highest with the lowest category) was associated with a statistically significant decreased risk of breast cancer among women with moderate or high alcohol consumption (summary estimate = 0.51, 95% CI = 0.41 to 0.63) but not among women with low or no alcohol consumption (summary estimate = 0.95, 95% CI = 0.78 to 1.15). Few studies examined whether the relation between folate intake and breast cancer was modified by intakes of methionine or vitamins B6 and B12, and the findings were inconsistent.No clear support for an overall relationship between folate intake or blood folate levels and breast cancer risk was found. Adequate folate intake may reduce the increased risk of breast cancer that has been associated with moderate or high alcohol consumption.
Multiple effects govern endogenous retrovirus survival patterns in human gene introns.
Authors: Louie N van de Lagemaat, Patrik Medstrand, Dixie L Mager
Journal: Genome biology (2006)

Endogenous retroviruses (ERVs) and solitary long terminal repeats (LTRs) have a significant antisense bias when located in gene introns, suggesting strong negative selective pressure on such elements oriented in the same transcriptional direction as the enclosing gene. It has been assumed that this bias reflects the presence of strong transcriptional regulatory signals within LTRs but little work has been done to investigate this phenomenon further. In the analysis reported here, we found significant differences between individual human ERV families in their prevalence within genes and degree of antisense bias and show that, regardless of orientation, ERVs of most families are less likely to be found in introns than in intergenic regions. Examination of density profiles of ERVs across transcriptional units and the transcription signals present in the consensus ERVs suggests the importance of splice acceptor sites, in conjunction with splice donor and polyadenylation signals, as the major targets for selection against most families of ERVs/LTRs. Furthermore, analysis of annotated human mRNA splicing events involving ERV sequence revealed that the relatively young human ERVs (HERVs), HERV9 and HERV-K (HML-2), are involved in no human mRNA splicing events at all when oriented antisense to gene transcription, while elements in the sense direction in transcribed regions show considerable bias for use of strong splice sites. Our observations suggest suppression of splicing among young intronic ERVs oriented antisense to gene transcription, which may account for their reduced mutagenicity and higher fixation rate in gene introns.
Psychological factors and asthma quality of life: a population based study
Authors: R J Adams
Journal: Thorax (2004)

<b>Background:</b> Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. <b>Methods:</b> The WANTS Health and Well-being Survey is a population household interview survey of adults (age ⩾18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: "Have you ever been told by a doctor that you have asthma?" and "Do you still have asthma?" determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. <b>Results:</b> From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% <i>v</i> 12.2%, p&lt;0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% <i>v</i> 31.2%, p&lt;0.01). Mental health conditions were also more common (16.2% <i>v</i> 10.8%, p&lt;0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% <i>v</i> 24.3%, p&lt;0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health—together with age, family's financial situation, education level, and number of days partially unable to work or perform usual duties—was significantly associated with scores on the PCS (<i>r</i> = 0.73, adjusted <i>r</i><sup>2</sup> = 0.54). <b>Conclusion:</b> These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.
Improvement of von Willebrand Factor Proteolysis After Prostacyclin Infusion in Severe Pulmonary Arterial Hypertension
Authors: Agnès Veyradier, Toshiya Nishikubo, Marc Humbert, Martine Wolf, Olivier Sitbon, Gérald Simonneau, Jean-Pierre Girma, Dominique Meyer
Journal: Circulation (2000)

Background —The presence of dysfunctional von Willebrand factor (vWF) in pulmonary arterial hypertension (PAH) was suggested to be related to increased proteolysis. Methods and Results —In 10 patients with severe PAH, we studied the proteolysis of plasma vWF (vWF levels, multimeric distribution, proteolytic pattern, and cleaving protease activity) and hemodynamic variables (mean pulmonary artery pressure, cardiac index, and total pulmonary vascular resistance) at baseline and 30 days after initiation of continuous prostacyclin infusion. At baseline, vWF levels were significantly increased, vWF proteolysis was excessive, and vWF-cleaving protease activity remained normal. These biological abnormalities were reversible and paralleled the improvement of hemodynamics under vasodilator treatment with prostacyclin. Conclusions —The excessive proteolysis of vWF in PAH is likely to be related to an increased susceptibility of vWF to proteases induced by high shear rates rather than to an enhanced release of enzymes.