2,758 research outputs found
Evaluation of plasma activity of matrix metalloproteinase-2 and -9 in dogs with myxomatous mitral valve disease
No full textTo investigate whether plasma activity of matrix metalloproteinase (MMP)-2 and -9 was associated with severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between MMP activity and dog characteristics, echocardiographic variables, systolic arterial blood pressure (SAP), heart rate, cardiac troponin I (cTnI) concentration, and C-reactive protein concentration.
ANIMALS:
75 client-owned dogs.
PROCEDURES:
Severity of MMVD was assessed by use of echocardiography. Plasma activity of latent (pro-MMP) and active MMP-2 and -9 was analyzed via zymography. Plasma concentration of cTnI was analyzed with a high-sensitivity cTnI assay, and C-reactive protein concentration was analyzed with a canine-specific ELISA.
RESULTS:
Pro-MMP-9, active MMP-9, and pro-MMP-2 were detected, but active MMP-2 was not. No significant differences were found in MMP concentrations among the 4 MMVD severity groups. Activity of pro-MMP-9 decreased with decreases in SAP and was higher in male dogs than in female dogs. Activity of MMP-9 decreased with increases in left ventricular end-systolic dimension and with decreases in SAP and cTnI concentration. Left ventricular end-systolic dimension was the variable most strongly associated with MMP-9 activity. No associations were found between the activity of pro-MMP-2 and investigated variables.
CONCLUSIONS AND CLINICAL RELEVANCE:
Plasma MMP-9 activity decreased with increases in the end-systolic left ventricular internal dimension and decreases in SAP. Hence, evaluation of MMP-9 activity has the potential to provide unique information about the myocardial remodeling process in dogs with MMVD
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
No full textG protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression
Writing a History of Women's Writing from 700 to 1500
No full textHow can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing
Writing a History of Women's Writing from 700 to 1500
No full textHow can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing
Blowout of non-premixed turbulent jet flames with coflow under microgravity condition
No full textThe blowout behavior of non-premixed turbulent coflow jet flames under microgravity environment was studied experimentally by utilizing a 3.6 s drop tower. Variations of flames leading to liftoff as well as blowout were examined by varying the coflow velocity and compared with those obtained under the normal gravity condition. A modeling work was conducted to incorporate the effects of the gravity (buoyancy) and coflow velocity on blowout behavior. Major findings include: (1) the flame length in microgravity was longer than that in normal gravity and decreased with increasing coflow velocity. The flame in microgravity showed more intense yellow luminosity with larger sooting zone; (2) the flame liftoff height increased with increasing coflow velocity in both gravity levels. The flame base was closer to the burner in microgravity as compared with that in normal gravity; (3) the blowout velocity in microgravity was appreciably larger than that obtained in normal gravity; and (4) a physical model based on Damkohler number was developed by using similarity solutions to characterize the differences in the blowout limits considering both the coflow and gravity (buoyancy) effects. The proposed model can successfully predict the experimental data. This work provided new data and basic scaling analysis for blowout limit of non-premixed turbulent jet flames considering both the coflow and gravity (buoyancy) effects. (C) 2019 The Combustion Institute. Published by Elsevier Inc. All rights reserved
Charles Berlitz, Author of "Doomsday," Takes Predictions
No full textCharles Berlitz, author of "Doomsday," makes predictions that life will cease after 2000 A.D
Suitability of Modified Dilute Double Acid ÐMehlich 1 (0.1NHCL + 0.025NH2SO4) and Olsen (0.5MNaHCO3PH 8.5) Methods for Testing of Available Phosphorous for Kenyan Soils
No full textA study was conducted to investigate the suitability of using modified Mehlich 1 and sodium bicarbonate Olsen methods for testing of available P for Kenyan soils. The soils were from 52 sites within the high and medium agricultural potential rainfall areas. Maize grain yields were used to calibrate the soil available P. The two P extraction methods were used at soil extracting ratio of 1:5. Regression analysis of maize grain yields (kg/ha) from plots with no fertilizer P application against extractable P by the two methods was done for the soil PH range: 4.0- 7.8, PH𕟭.5, 5.6≤PH £6.4 and 6.5 ≤PH£ 7.8. Similar regression analysis was done for HB-600S and HB500S maize varieties and agro ecological zones (UM, LH, UH, LM and CL). Further regression was done taking into account of different prevailing agro-ecological zones. The results revealed that maize grain yields (kg/ha) were significantly (P𕟨.015) correlated (r= 0.335) to soil available P extractable by Olsen method and not modified dilute double acid Mehlich 1 method at soil PH range of 4.0-7.8. These results showed that available P can be estimated by the sodium bicarbonate method although the correlation was very small (r =0.335) but significant. The very small significant correlation implied need for further regression with more soil data. When regression analysis was done at soil PH 𕟭.5 the correlations for both methods were not significant. This meant that both test methods were not suitable for estimating available P at this soil PH range and another suitable method should be found for soils within this PH range. At 5.6≤PH£ 6.4, both methods were significantly, (P𕟨.05) suitable with improved correlations (r = 0.488 and r= 0.490). This meant that at this soil PH range, both methods were suitable and can be used interchangeably although Olsen method gave lower values of available P than the double acid method. At 6.5≤PH £7.8, both methods were not significant and hence not suitable for estimating available P. When maize varieties HB 600 and HB 500 series were
taken into account. It was found that both methods were significantly (P𕟨.05) suitable for estimating soil available P for planting maize HB 600 series. Only Olsen P method was significantly suitable (P≤ 0.011) for estimating soil available P for planting maize HB 500 & 600 series. When agro ecological zones were taken into account, both methods were found significantly (P𕟨.05) suitable for estimating available P in LH zones only. It was concluded that Olsen method is significantly suitable for testing of available P at all soil PH range while modified Mehlich 1 method is not. The two methods are not suitable at PH≤ 5.5 and another method must be found. At 5.6≤ PH≤ 6.4, both methods can be used interchangeably. At 6.5≤PH𕟯.8 both methods are not suitable. This was attributed to over extraction by the modified dilute double acid and laboratory errors associated with Olsen method particularly on increase in pH of extracting solution when not kept in plastic containers. This leads to over extraction and hence poor correlation with crop yields. Olsen P method is suitable for estimating available P for planting maize HB 600 and HB 500 series. Both methods are not suitable for estimating available P in UM; LM and CL zones but are suitable in LH zones. In overall Olsen method appeared to be slightly suitable method for estimating available P in Kenyan soils and can be used interchangeably with modified Mehlich 1 at soil PH, 5.6≤ PH𕟮.4. However the small significant (p𕟨.015, r= 0.335) correlation meant more research was required to correlate other soil P testing methods for Kenyan soils. Keywords:Soil pH, P-testing, crop response and correlationsDiscovery and Innovation Vol. 19 (3) 2007: pp. 195-20
IMMUNOCYTOLOGICAL EVIDENCE OF LH-RF IN HYPOTHALAMUS AND MEDIAN EMINENCE : A REVIEW
No full textInternational audienceThe author reviews reports about the immunocytological demonstration of LH-RF in the hypothalamus and describes the materials and methods used by different groups of workers. The different authors are in agreement about the localization of LH-RF axons and axonal endings. The hypothalamo-infundibular pathway, which is the principal LH-RF neurosecretory pathway, and the accessory extra-hypophyseal pathways in guinea-pig, dog, cat and primates, and the distribution of LH-RF in the median eminence of ram, birds (cock, duck) and amphibians (toad, xenopus, triton) are described
Deletion of arcuate nucleus-specific Kiss1 disrupts estrous cyclicity and LH pulsatility in female mice
No full textKisspeptin (encoded by Kiss1), a neuropeptide critically involved in neuroendocrine regulation of reproduction, is primarily synthesized in two discrete hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Current data indicates that AVPV Kiss1 is important for the pre-ovulatory luteinizing hormone (LH) surge unique to females as well as estrogen-induced positive feedback control of GnRH and LH. In contrast, ARC Kiss1 neurons, which largely co-express the neuropeptides NKB and dynorphin (collectively known as KNDy neurons), are thought to be the major regulators of pulsatile release of GnRH and LH, and mediate estrogen- induced negative feedback control of both GnRH and LH. Previous studies have not definitively separated the specific roles of Kiss1 in the AVPV versus KNDy-ARC neurons in the downstream control of GnRH and LH release. Therefore, we generated a Pdyn-Cre/Kiss1fl/fl (KO) mouse model to target Kiss1 in KNDy neurons to differentiate KNDy neuron-specific function from AVPV Kiss1 function in the maturation and maintenance of the reproductive axis. qRT-PCR data documented the loss of Kiss1 expression in the mediobasal hypothalamus (containing ARC) compared to controls, whereas Kiss1 in the preoptic area (containing AVPV) was similar in both KO and controls. Immunofluorescent staining for kisspeptin confirmed the loss of Kiss1 specifically in the ARC of KO mice. Although no changes in pubertal body weight gain or pubertal onset were observed in KO animals, KO females exhibited disrupted estrous cyclicity in adulthood. Interestingly, KO female mice had disrupted estrous cycles presenting with persistent diestrus and a small vaginal opening. We tested the hypothesis that ARC KNDy neurons are necessary for generating and maintaining episodic LH pulsatile release by serial collection of whole blood and measuring LH. KO female mice exhibited significantly fewer LH pulses in a 3-hour timespan compared to controls, suggesting that KNDy neurons were functionally compromised. These observations indicate the central role of KNDy neurons in the regulation of GnRH/LH pulsatility and estrous cyclicity. The functional effects of disrupted estrous cyclicity and slowed LH pulsatility observed in KO females result in arrested folliculogenesis and infertility. Future experiments will determine whether ARC Kiss1 deletion disrupts the KNDy- driven negative feedback response of LH to gonadectomy, as well as address potential sex differences in ARC Kiss1-mediated negative feedback control of LH release.M.S.Includes bibliographical reference
Accuracy of the hypospadias diagnoses and surgical treatment registrations in the Danish National Patient Register
No full textLinn Håkonsen Arendt,1,2,* Andreas Ernst,1,3,* Morten Søndergaard Lindhard,2 Anne Aggerholm Jønsson,1 Tine Brink Henriksen,2 Jørn Olsen,4 Jorgen Thorup,5 L Henning Olsen,3 Cecilia Høst Ramlau-Hansen1 *These authors contributed equally to this work 1Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; 2Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Urology, Section for Paediatric Urology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 5Department of Paediatric Surgery, Rigshospitalet and Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Purpose: The Danish National Health registers provide a valuable data source that offers unique opportunities for observational research, including studies on the congenital anomaly hypospadias. The accuracy of the diagnosis and surgical treatment registration of hypospadias in the Danish National Patient Register (DNPR) remains unknown. Patients and methods: We randomly sampled 500 patients diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012. Among these, 384 patients were also registered with surgical treatment for hypospadias. Medical records were collected and reviewed independently by two investigators. Any classification disagreements were resolved by consensus. Using the medical records as the gold standard, we estimated positive predictive values (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and surgical treatment registrations overall, as well as for the clinical subtypes. Results: We were able to retrieve medical records for 463 (92.6%) patients with hypospadias diagnoses and for 329 (85.7%) patients registered with surgical treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding an overall PPV (95% CI) of 97.6% (95.8%–98.7%). For subtypes of hypospadias, the PPVs ranged between 37.5% and 72.7%. For surgical treatment of hypospadias, the overall PPV was 99.7% (97.9%–99.9%). Conclusion: The validity of the registration of hypospadias diagnoses as well as surgical treatment for hypospadias in the DNPR is overall very high. For the specific subtypes of hypospadias diagnoses codes and the specific surgical treatment codes, the PPVs are lower and cautious use is warranted. However, the DNPR remains a valuable tool for future observational research on hypospadias. Keywords: data quality, epidemiology, hospital register diagnoses, ICD-10, positive predictive valu
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