tbuckley/cabot-search huggingface dataset:
Low Nucleotide Diversity for the Expanded Organelle and Nuclear Genomes of Volvox carteri Supports the Mutational-Hazard Hypothesis
Authors: D. R. Smith, R. W. Lee
Journal: Molecular Biology and Evolution (2010)

The noncoding-DNA content of organelle and nuclear genomes can vary immensely. Both adaptive and nonadaptive explanations for this variation have been proposed. This study addresses a nonadaptive explanation called the mutational-hazard hypothesis and applies it to the mitochondrial, plastid, and nuclear genomes of the multicellular green alga Volvox carteri. Given the expanded architecture of the V. carteri organelle and nuclear genomes (60-85% noncoding DNA), the mutational-hazard hypothesis would predict them to have less silent-site nucleotide diversity (π(silent)) than their more compact counterparts from other eukaryotes-ultimately reflecting differences in 2N(g)μ (twice the effective number of genes per locus in the population times the mutation rate). The data presented here support this prediction: Analyses of mitochondrial, plastid, and nuclear DNAs from seven V. carteri forma nagariensis geographical isolates reveal low values of π(silent) (0.00038, 0.00065, and 0.00528, respectively), much lower values than those previously observed for the more compact organelle and nuclear DNAs of Chlamydomonas reinhardtii (a close relative of V. carteri). We conclude that the large noncoding-DNA content of the V. carteri genomes is best explained by the mutational-hazard hypothesis and speculate that the shift from unicellular to multicellular life in the ancestor that gave rise to V. carteri contributed to a low V. carteri population size and thus a reduced 2N(g)μ. Complete mitochondrial and plastid genome maps for V. carteri are also presented and compared with those of C. reinhardtii.
Respiratory Disorders Associated with Impairment of Gas Diffusion (Alveolo-Capillary Block Syndrome)
Authors: D V Bates
Journal: Annual Review of Medicine (1962)

membrane or pulmonary capil lary, but also by the surface area available for gas exchange. In addition, the diffusing capacity may be affecte d by the speed of passage of blood through the capillary bed. With the exception of simple situations (such as the study of patients with only one lung), com­ mon disorders associated with a loss of internal surface area of the lung are usually accompanied by extremely severe disturbances of the distribu­ tion of ventilation and perfusion within the lung. Pulmonary emphysema represents the most common example of this kind of situation; and for rea­ sons which need not be discusse d here, the interpretation of measurements of the pulmonary diffusing capacity in a grossly uneven system is uncertain. In the majority of instances in which the diffusion defect is caused by qualitative changes of the alveolar membrane, there is not such a gross dis­ turbance of gas and blood distribution, although the unevenness which may exist has been shown to be far from negligible in these disorders (10). Nevertheless, the different techniques available for the measurement of diffusing capacity have given fairly uniform results when employed in the study of these diseases. The process of diffusion at the alveolar capillary level is invariably one of a race between the potential spee d of oxygen transfer and the time during which the blood is exposed to alveolar gas. H the alveolar membrane is thickened, the oxygen tension of blood leaving the pulmonary capillary is bound to fall if the time during which it re­ mains in the alveolus is not prolonged. This situation is seen clinically in the desaturation which may be obser ved during exercise in patients with severe interstitial fibrosis of the lungs, since the reduction in transit time through the capillary may result in arterial unsaturation. This review attempts to summarize material which has been published on many different pulmonary conditions. The bibliography represents only 1 The survey of literature pertaining to this review was concluded September,
Critical Role of Monocyte Chemoattractant Protein-1 Receptor CCR2 on Monocytes in Hypertension-Induced Vascular Inflammation and Remodeling
Authors: Minako Ishibashi, Ken-ichi Hiasa, Qingwei Zhao, Shujiro Inoue, Kisho Ohtani, Shiro Kitamoto, Miyuki Tsuchihashi, Takeshi Sugaya, Israel F. Charo, Shinobu Kura, Teruhisa Tsuzuki, Tatsuro Ishibashi, Akira Takeshita, Kensuke Egashira
Journal: Circulation Research (2004)

Activated monocytes are present in the arterial walls of hypertensive patients and animals. Monocyte chemoattractant protein-1 (MCP-1), which controls monocyte function through its receptor (CCR2), is implicated in hypertensive inflammatory changes in the arterial wall. The role of CCR2 expression on monocytes in hypertension-induced vascular remodeling, however, has not been addressed. We hypothesized that CCR2 on monocytes is critical in hypertension-induced vascular inflammation and remodeling. Hypertension was induced by infusion of angiotensin II (Ang II) into wild-type mice, CCR2-deficient (CCR2-/-) mice, and bone marrow-transferred mice with a leukocyte-selective CCR2 deficiency (BMT-CCR2-/-). In wild-type mice, Ang II increased CCR2 intensity in circulating monocytes, which was prevented by an Ang II type-1 (AT1) receptor blocker or blunted in AT1 receptor-deficient mice. Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice. In CCR2-/- and BMT-CCR2-/- mice, Ang II-induced vascular inflammation and vascular remodeling (aortic wall thickening and fibrosis) were blunted as compared with control mice. In contrast, Ang II-induced left ventricular hypertrophy developed in CCR2-/- and BMT-CCR2-/- mice. The present study suggests that CCR2 expression in monocytes has a critical role in vascular inflammation and remodeling in Ang II-induced hypertension, and possibly in other forms of hypertension.
THE MOTOR CAR SHOW IN RETROSPECT
Authors: H. M. Buist
Journal: BMJ (1912)

THE Motor Exhibition which closed at Olympia, Ken- sington, on November 16tll contained such a multitude of novelties, all chiefly of a minor character, that it has been almost impossible to make acquaintance with all in the eiglht days during which the display has been open to the public.But the first and last impression is still that the miiain advance has been the tendency to fit self-starters and the further growth of the use of electric lighting systems, for plant are now being made on a smaller scale to suit middle and low-powered cars and slender.
Long-Term Depression of Kainate Receptor-Mediated Synaptic Transmission
Authors: Yunkyung Park, Jihoon Jo, John T.R. Isaac, Kwangwook Cho
Journal: Neuron (2006)

Kainate receptors (KARs) have been shown to be involved in hippocampal mossy fiber long-term potentiation (LTP); however, it is not known if KARs are involved in the induction or expression of long-term depression (LTD), the other major form of long-term synaptic plasticity. Here we describe LTD of KAR-mediated synaptic transmission (EPSCKA LTD) in perirhinal cortex layer II/III neurons that is distinct from LTD of AMPAR-mediated transmission, which also coexists at the same synapses. Induction of EPSCKA LTD requires a rise in postsynaptic Ca2+ but is independent of NMDARs or T-type voltage-gated Ca2+ channels; however, it requires synaptic activation of inwardly rectifying KARs and release of Ca2+ from stores. The synaptic KARs are regulated by tonically activated mGluR5, and expression of EPSCKA LTD occurs via a mechanism involving mGluR5, PKC, and PICK1 PDZ domain interactions. Thus, we describe the induction and expression mechanism of a form of synaptic plasticity, EPSCKA LTD.
DC-SCRIPT: Nuclear Receptor Modulation and Prognostic Significance in Primary Breast Cancer
Authors: M. Ansems, S. Hontelez, M. W. G. Looman, N. Karthaus, P. Bult, J. J. Bonenkamp, J. H. Jansen, F. C. G. J. Sweep, P. N. Span, Gosse J. Adema
Journal: JNCI Journal of the National Cancer Institute (2009)

Nuclear receptors, including estrogen receptor (ER), progesterone receptor (PR)-B, peroxisome proliferator-activated receptor gamma, and retinoic acid receptor alpha, have been implicated in breast cancer etiology and progression. We investigated the role of dendritic cell-specific transcript (DC-SCRIPT) as coregulator of these nuclear receptors and as a prognostic factor in breast cancer.The effect of DC-SCRIPT on the transcriptional activity of nuclear receptors was assessed by luciferase reporter assays. DC-SCRIPT expression in normal and tumor tissue from breast cancer patients was analyzed by polymerase chain reaction and immunohistochemistry. The prognostic value of tumor DC-SCRIPT mRNA expression was assessed in three independent cohorts of breast cancer patients: a discovery group (n = 47) and a validation group (n = 97) (neither of which had received systemic adjuvant therapy) and in a tamoxifen-treated validation group (n = 68) by using a DC-SCRIPT to porphobilinogen deaminase transcript ratio cutoff of 0.15 determined in the discovery group. Univariate and multivariable Cox proportional hazards model analyses were performed. All statistical tests were two-sided.DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the retinoic acid receptor alpha- and peroxisome proliferator-activated receptor gamma-mediated transcription. In breast tissue samples from nine patients, DC-SCRIPT mRNA was expressed at lower levels in the tumor than in the corresponding normal tissue (P = .010). Patients in the discovery group with high tumor DC-SCRIPT mRNA levels (66%) had a longer disease-free interval than those with a low DC-SCRIPT mRNA level (34%) (hazard ratio [HR] of recurrence for high vs low DC-SCRIPT level = 0.23, 95% confidence interval [CI] = 0.06 to 0.93, P = .039), which was confirmed in the validation group (HR of recurrence = 0.50, 95% CI = 0.26 to 0.95, P = .034). This prognostic value was confined to patients with ER- and/or PR-positive tumors (discovery group: HR of recurrence = 0.16, 95% CI = 0.03 to 0.89, P = .030; validation group: HR of recurrence = 0.42, 95% CI = 0.19 to 0.91, P = .028) and was also observed in the second validation group (HR = 0.46, 95% CI = 0.22 to 0.97, P = .040). DC-SCRIPT was an independent prognostic factor after correction for tumor size, lymph node status, and adjuvant therapy (n = 145; HR = 0.50, 95% CI = 0.29 to 0.85, P = .010).DC-SCRIPT is a key regulator of nuclear receptor activity that has prognostic value in breast cancer.
Identification of Markers of Taxane Sensitivity Using Proteomic and Genomic Analyses of Breast Tumors from Patients Receiving Neoadjuvant Paclitaxel and Radiation
Authors: Joshua A. Bauer, A. Bapsi Chakravarthy, Jennifer M. Rosenbluth, Deming Mi, Erin H. Seeley, Nara De Matos Granja-Ingram, Maria G. Olivares, Mark C. Kelley, Ingrid A. Mayer, Ingrid M. Meszoely, Julie A. Means-Powell, Kimberly N. Johnson, Chiaojung Jillian Tsai, Gregory D. Ayers, Melinda E. Sanders, Robert J. Schneider, Silvia C. Formenti, Richard M. Caprioli, Jennifer A. Pietenpol
Journal: Clinical Cancer Research (2010)

To identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies.Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR).Proteomic and validation immunohistochemical analyses revealed that alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery.We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane-based therapy.
Mediation of immune glomerular injury.
Authors: W G Couser
Journal: Journal of the American Society of Nephrology (1990)

This paper reviews current concepts of glomerular immune injury of both inflammatory and noninflammatory types. In noninflammatory lesions induced by antibody alone or C5b-9, the glomerular epithelial cell appears to be the principal target of injury. Similar mechanisms are probably operative in human diseases such as minimal change nephrotic syndrome and membranous nephropathy. In inflammatory lesions, circulating effector cells including neutrophils, macrophages, platelets, and probably lymphocytes as well as resident glomerular mesangial cells may mediate tissue injury. Human equivalents of these inflammatory lesions include most diseases associated with mesangial and/or subendothelial immune deposits and/or mesangial cell proliferation. Neutrophil-mediated injury appears to be consequent to both proteinases and oxidants, particularly the myeloperoxidase-H2O2-halide system. Platelets may be critically involved in neutrophil mediated injury as well. Platelets also mediate mesangial cell proliferation, probably by a release of platelet growth factors and stimulation of mesangial cell platelet-derived growth factor and platelet-derived growth factor receptor expression. Immunologically induced mesangial cell proliferation is associated with increased production of nephritogenic proteinase in vivo.
Bone mineral density in Australian children, adolescents and adults with cystic fibrosis: a controlled cross sectional study
Authors: H M Buntain
Journal: Thorax (2004)

<b>Background:</b> Low bone mineral density (BMD) is recognised in individuals with cystic fibrosis (CF) although the pathogenesis remains unclear. The aims of this study were to compare BMD over a broad continuum of Australian individuals with CF with healthy controls and to examine the relationship between BMD and clinical parameters including physical activity, nutrition, and vitamin D levels. <b>Methods:</b> BMD of the lumbar spine (LS), total body (TB), femoral neck (FN), cortical wrist (R33%), and distal wrist (RUD) was examined in 153 individuals with CF aged 5.3–55.8 years (84 males) and in 149 local controls aged 5.6–48.3 years (66 males) using dual energy <i>x</i> ray absorptiometry. Anthropometric variables, body cell mass, markers of disease severity, corticosteroid usage, measures of physical activity, dietary calcium and caloric intake and serum vitamin D were assessed and related to BMD. <b>Results:</b> Compared with controls, mean BMD was not significantly different in children aged 5–10 years with CF. Adolescents (females 11–18 years, males 11–20 years) had reduced TB and R33% BMD when adjusted for age, sex, and height (difference in BMD (g/cm<sup>2</sup>) adjusted means between control and CF: TB = 0.04 (95% CI 0.01 to 0.07); R33% = 0.03 (95% CI 0.01 to 0.06)). BMD was reduced at all sites except R33% in adults (difference in BMD (g/cm<sup>2</sup>) adjusted means between control and CF: TB = 0.05 (95% CI 0.02 to 0.09); LS = 0.08 (95% CI 0.03 to 0.14); FN = 0.09 (95% CI 0.03 to 0.15); RUD = 0.03 (95% CI 0.01 to 0.05)). In children/adolescents BMD was weakly associated with nutritional status and disease severity. <b>Conclusions:</b> BMD was normal in a well nourished group of prepubertal children with CF. A BMD deficit appears to evolve during adolescence and becomes more marked in adults. Individuals with CF should optimise nutrition, partake in physical activity, and maximise lung health in order to optimise BMD. Further longitudinal studies are required to understand the evolution of reduced BMD in young people and adults with CF.
HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance
Authors: Kideok Jin, Sunju Park, Wei Wen Teo, Preethi Korangath, Sean Soonweng Cho, Takahiro Yoshida, Balázs Győrffy, Chirayu Pankaj Goswami, Harikrishna Nakshatri, Leigh-Ann Cruz, Weiqiang Zhou, Hongkai Ji, Ying Su, Muhammad Ekram, Zhengsheng Wu, Tao Zhu, Kornelia Polyak, Saraswati Sukumar
Journal: Cancer Discovery (2015)

Abstract Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor-α (ERα) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 chromatin immunoprecipitation analysis followed by validation showed that HOXB7 physically interacts with ERα, and that the HOXB7–ERα complex enhances transcription of many ERα target genes, including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR–HER2 signaling, inhibits transcription of miR-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER target genes, and HER2. Repressing MYC using small-molecule inhibitors reverses these events and causes regression of breast cancer xenografts. The MYC–HOXB7–HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer. Significance: HOXB7 acts as an ERα cofactor regulating a myriad of ER target genes, including HER2, in tamoxifen-resistant breast cancer. HOXB7 expression is controlled by MYC via transcriptional regulation of the HOXB7 repressor miR-196a; consequently, antagonists of MYC cause reversal of selective ER modulator resistance both in vitro and in vivo. Cancer Discov; 5(9); 944–59. ©2015 AACR. See related commentary by Heideman et al., p. 909. This article is highlighted in the In This Issue feature, p. 893
T cell reactivity against the SmD183-119 C terminal peptide in patients with systemic lupus erythematosus
Authors: G Riemekasten
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> The SmD1<sub>83–119</sub> peptide is a major target of the B cell response in patients with systemic lupus erythematosus (SLE). <b>Objective:</b> To investigate the T cell response directed against this peptide, its disease specificity, and possible impact on SLE pathogenesis. <b>Methods:</b> Peripheral blood mononuclear cells derived from 28 patients with SLE and 29 healthy and disease controls were stimulated by the SmD1<sub>83–119</sub> and the recombinant (r)SmD1 protein, and [<sup>3</sup>H]thymidine incorporation was measured. Patients with SLE were simultaneously tested for autoantibodies, disease activity, clinical symptoms, and medical treatments. <b>Results:</b> T cell reactivity against the SmD1<sub>83–119</sub> peptide was detected in 11/28 (39%) patients with SLE and against the rSmD1 protein in 10/28 (36%) patients. In contrast, only 2/29 (7%) controls exhibited SmD1 reactivity. An analysis of proliferation kinetics showed that SmD1 reactive T cells are activated in vivo, as additionally confirmed by cytometric analysis. Addition of mammalian dsDNA to rSmD1 enhanced the rSmD1-specific T cell response. SmD1<sub>83–119</sub>-specific T cell reactivity was significantly more common in patients with cardiac and pulmonary symptoms. No correlation between T and B cell responses and disease activity was seen. <b>Conclusion:</b> SmD1<sub>83–119</sub> is a major T cell epitope of SmD1, commonly recognised by T cells from patients with SLE and much less commonly found by healthy or disease controls. This strong T cell reactivity as well as the high frequency and specificity of anti-SmD1<sub>83–119</sub> antibodies in SLE suggest a possible role in SLE pathogenesis, at least in a subset of patients.
Inpatient disposition classification for the creation of hospital surge capacity: a multiphase study
Authors: Gabor D Kelen, Chadd K Kraus, Melissa L McCarthy, Eric Bass, Edbert B Hsu, Guohua Li, James J Scheulen, Judy B Shahan, Justin D Brill, Gary B Green
Journal: The Lancet (2006)

BackgroundThe ability to provide medical care during sudden increases in patient volume during a disaster or other high-consequence event is a serious concern for health-care systems. Identification of inpatients for safe early discharge (ie, reverse triage) could create additional hospital surge capacity. We sought to develop a disposition classification system that categorises inpatients according to suitability for immediate discharge on the basis of risk tolerance for a subsequent consequential medical event.MethodsWe did a warfare analysis laboratory exercise using evidence-based techniques, combined with a consensus process of 39 expert panellists. These panellists were asked to define the categories of a disposition classification system, assign risk tolerance of a consequential medical event to each category, identify critical interventions, and rank each (using a scale of 1–10) according to the likelihood of a resultant consequential medical event if a critical intervention is withdrawn or withheld because of discharge.FindingsThe panellists unanimously agreed on a five-category disposition classification system. The upper limit of risk tolerance for a consequential medical event in the lowest risk group if discharged early was less than 4%. The next categories had upper limits of risk tolerance of about 12% (IQR 8–15%), 33% (25–50%), 60% (45–80%) and 100% (95–100%), respectively. The expert panellists identified 28 critical interventions with a likelihood of association with a consequential medical event if withdrawn, ranging from 3 to 10 on the 10-point scale.InterpretationThe disposition classification system allows conceptual classification of patients for suitable disposition, including those deemed safe for early discharge home during surges in demand. Clinical criteria allowing real-time categorisation of patients are awaited.
Effect of Hypophysectomy on Cardiovascular Actions of ACTH and STH
Authors: ERNESTO D. SALGADO
Journal: Circulation Research (1957)

These experiments indicate that the pituitary adrenocorticotropic hormone (ACTH) and somato trophic hormone (STH) share the ability to produce hypertension, nephroselerosis, myocarditis and periarteritis nodosa in the intact rat. In the absence of the hypophysis rise in arterial pressure was less and no vascular lesions were observed.