Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional role of beta2-adrenoceptors in the transplanted human heart.

In the transplanted human heart, beta-adrenoceptor subtypes change with time after transplantation: beta1-adrenoceptors tend to decline, whereas beta2-adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of beta2-adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time: 932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the beta1-adrenoceptor antagonist bisoprolol (10 mg p.o.; beta1-adrenoceptor occupancy approximately 80%; beta2-adrenoceptor occupancy <5%) on heart rate in the recipient's native (innervated) and transplanted (denervated) sinus nodes. Isoprenaline, acting under these conditions predominantly at beta2-adrenoceptors, increased heart rate both in the recipient's transplanted and native sinus nodes in a dose-dependent manner; at each dose, increases were significantly higher in the transplanted than in the native sinus node. ED20 values (dose to increase heart rate by 20 beats/min) in the transplanted sinus node were 22.2 +/- 1.8 ng/kg/min, and in the native, >35 ng/kg/min (p < 0.01). We conclude that in the transplanted human heart, beta2-adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated beta2-adrenoceptors or by the fact that during isoprenaline infusion, vagal activity increases, thus blunting the response in the native (innervated) but not in the transplanted (denervated) sinus node.
Neural activity of the cardiac baroreflex decreases with age in normotensive and hypertensive subjects

Objectives Baroreflex control of the heart rate is impaired in hypertensive subjects and decreases with age. The decrease in cardiac baroreflex sensitivity (BRS) is often ascribed to decreased distension of the pressure-sensing arterial wall segments. However, alterations in the sensing and processing of neural signals may be involved as well. Design Conventionally, both vessel wall stiffness and the sensing and neural processing of the baroreflex are incorporated in the measure of pressure-derived BRS. We introduce stretch-derived BRS, which only considers the sensing and neural components of the baroreflex. Methods To determine stretch-derived BRS in a non-invasive manner, we measured the spontaneously occurring low-frequency variations (range, 0.06–0.12 Hz) in the carotid artery diameter and the corresponding R–R interval fluctuations, and determined the associated transfer function. The stretch-derived BRS in a group of age-matched (age range, 25–72 years) normotensive (n = 20) and hypertensive (n = 21) subjects was compared. Results In both subject groups the stretch-derived BRS decreased significantly with age. Moreover, the stretch-derived BRS of both groups was only different below 50 years of age. Conclusions The analysis of low-frequency fluctuations in the carotid artery diameter demonstrates that aging as well as hypertension are associated with impaired neural control of the baroreflex. Beyond 50 years of age the effect of hypertension cannot be distinguished from the effect of aging.
A Transactivator Function of Cottontail Rabbit Papillomavirus E2 Is Essential for Tumor Induction in Rabbits

ABSTRACT Infection of domestic rabbits with cottontail rabbit papillomavirus (CRPV) causes local papillomas which progress to carcinomas in more than 80% of cases. This animal model system therefore allows the identification of molecular mechanisms required for the induction and progression of epithelial tumors. The viral E2 protein stimulates both viral DNA replication and transcription, and these functions can be genetically separated. We introduced the respective mutations into CRPV E2 and found, in line with published data for other papillomavirus E2 proteins, that mutation of the highly conserved amino acid 37 or 73 resulted in replication-competent but transactivation-deficient E2 proteins, whereas E2 proteins with mutations at residue 39 were replication deficient and transactivation competent. The R37A, I73L, and I73A E2 mutants, showing a loss of transactivation function, and the R37K E2 mutant, which is still transactivation competent, were introduced into the whole genome of CRPV, which was then injected into the skin of rabbits. Strikingly, the ability to induce tumors within 6 weeks was abolished by each of the E2 mutations, in contrast to the tumor induction rate (93%) obtained with wild-type CRPV DNA. Two small papillomas induced by mutant E2 I73A CRPV DNA appeared as late as 12 or 24 weeks postinjection, were significantly smaller, and showed no further extension of growth. These data suggest that functionally conserved amino acids in the transactivation domain of E2 are also required for the induction and growth of epithelial tumors in rabbits infected with CRPV.
Melatonin Controls Seasonal Breeding by a Network of Hypothalamic Targets

In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible for the seasonal timing of reproduction, but the anatomical substrates and the cellular mechanisms through which melatonin modulates seasonal functions remain imprecise. Recently, several genes have been identified as being regulated by the photoperiod in the brain of seasonal mammals. These genes are thought to play active roles in the regulation of seasonal biology, notably for the adjustment of reproduction and body weight. Here, we briefly review findings associated with the control of seasonal breeding and describe recent data ascribing photoperiodic roles to type 2 and type 3 deiodinases, to the Kiss1/GPR54 system and to the RFamide-related peptides.Interestingly, these systems involve different hypothalamic nuclei, suggesting that several brain loci may be crucial for melatonin to regulate reproduction, and thus represent key starting points to identify the long-sought-after mode and site(s) of action of melatonin. Such findings raise great hopes for the future and could herald a new era of research in the field of seasonal biology.
FlhB Regulates Ordered Export of Flagellar Components via Autocleavage Mechanism*

The bacterial flagellum is a predominantly cell-external super-macromolecular construction whose structural components are exported by a flagellum-specific export apparatus. One of the export apparatus proteins, FlhB, regulates the substrate specificity of the entire apparatus; i.e. it has a role in the ordered export of the two main groups of flagellar structural proteins such that the cell-proximal components (rod-/hook-type proteins) are exported before the cell-distal components (filament-type proteins). The controlled switch between these two export states is believed to be mediated by conformational changes in the structure of the C-terminal cytoplasmic domain of FlhB (FlhBC), which is consistently and specifically cleaved into two subdomains (FlhBCN and FlhBCC) that remain tightly associated with each other. The cleavage event has been shown to be physiologically significant for the switch. In this study, the mechanism of FlhB cleavage has been more directly analyzed. We demonstrate that cleavage occurs in a heterologous host, Saccharomyces cerevisiae, deficient in vacuolar proteinases A and B. In addition, we find that cleavage of a slow-cleaving variant, FlhBC(P270A), is stimulated in vitro at alkaline pH. We also show by analytical gel-filtration chromatography and analytical ultracentrifugation experiments that both FlhBC and FlhBC(P270A) are monomeric in solution, and therefore self-proteolysis is unlikely. Finally, we provide evidence via peptide analysis and FlhB cleavage variants that the tertiary structure of FlhB plays a significant role in cleavage. Based on these results, we propose that FlhB cleavage is an autocatalytic process.
Postnatal development and adult organisation of the olivocerebellar projection map in the hypogranular cerebellum of the rat

The olivocerebellar system is characterised by a precise topographical organisation, in which distinct subsets of inferior olivary axons project to neurochemically heterogeneous Purkinje cell subpopulations, arranged into parasagittally oriented compartments in the cerebellar cortex. Adult climbing fibres and Purkinje cells are linked by a one‐to‐one relationship, which is established during postnatal development after a transitory phase of multiple climbing fibre innervation. The elimination of redundant climbing fibre synapses is thought to be regulated by granule cell‐mediated activity‐dependent processes. In order to assess whether this developmental remodelling is also important for the construction of the mature olivocerebellar projection map, we examined the hypogranular cerebella of rats treated by means of methylazoxymethanol acetate (MAM) during early postnatal life, in which multiple climbing fibre innervation persists in the adult. In these animals we investigated the distribution of calcitonin gene‐related peptide (CGRP)‐immunoreactive olivocerebellar axons and arbours during early postnatal development, and the correspondence between climbing fibre strips and zebrin II‐defined Purkinje cell bands in the adult. Our results show that: (1) the pattern of CGRP‐immunoreactive climbing fibres observed during the first three postnatal weeks is not disrupted after granule cell degeneration; and (2) the alignment between olivocerebellar axon subsets and zebrin II+/− Purkinje cell compartments is normally achieved in adult rats. In contrast, the climbing fibre‐Purkinje cell relationship is abnormal, and single arbours innervate restricted dendritic regions of several neighbouring target neurons. These results indicate that the normal distribution of olivocerebellar axon subsets to distinct cerebellar cortical compartments can be established independently from granule cell‐mediated remodelling processes. Thus, the postnatal climbing fibre plasticity, which is needed to achieve the normal climbing fibre‐Purkinje cell relationship, appears to be confined within the framework of a projection map established during earlier developmental phases. J. Comp. Neurol. 407:527–542, 1999. © 1999 Wiley‐Liss, Inc.
Canines as Sentinels for Lyme Disease in San Diego County, California

Prevalence of Lyme borreliosis in canine sentinels has been shown to correlate with infection in humans. One thousand canine sera (917 dogs, 83 coyotes) obtained from animal control authorities and area veterinarians were screened by ELISA for antibodies to Borrelia burgdorferi. Results were validated by Western blot and indirect fluorescent antibody (IFA) tests at referee laboratories. Criterion for a positive Western blot was presence of 5 of 10 of the most common antigen IgG bands; for IF A, >1:128 or the equivalent when correcting for interlaboratory variability. Twenty-two of 1,000 canines were confirmed serologically positive (21 dogs and 1 coyote; seroprevalence 2.3% and 1.2%, respectively). Lifestyle, breed size, gender, and age were not statistically predictive of seropositive status. No regional clustering of seropositive animals was detected. The low prevalence of seropositivity in sentinel canines suggests the Lyme borreliosis hazard in San Diego County is minimal.
Coronary artery bypass grafting in Canada: national and provincial mortality trends, 1992-1995.

BACKGROUND Despite a body of research on outcomes of coronary artery bypass grafting (CABG) in Canada, little is known about Canada-wide outcome trends and interregional differences in outcome. The objectives of this study were to examine Canadian trends in rates of in-hospital death after CABG and to compare provincial risk-adjusted death rates. METHODS Hospital discharge data were obtained from the Canadian Institute for Health Information and were used to identify complete cohorts of patients who underwent CABG in 8 provinces in fiscal years 1992/93 through 1995/96. Data from Quebec hospitals were not available. A logistic regression model was used to calculate risk-adjusted death rates by year, province, and province and year. RESULTS A total of 50,357 CABG cases were studied, with an overall death rate of 3.6%. A national trend of decreasing mortality was found, with a risk-adjusted death rate of 3.8% in 1992/93 versus 3.2% in 1995/96 (relative decrease of 17%) (p < 0.001 for difference across years). Some provinces (e.g., Alberta, Manitoba and Ontario) achieved overall declines in death rates over the study period, whereas others (e.g., British Columbia and Saskatchewan) did not. The average severity of illness of patients who underwent CABG differed considerably across provinces. Despite risk adjustment for these differences, provincial death rates varied significantly (p < 0.001). INTERPRETATION Rates of death after CABG in Canada decreased significantly in a relatively short period. Despite this encouraging finding, there were interprovincial differences in severity of illness and risk-adjusted death rates. This finding raises the possibility of unequal access to CABG and variable quality of care for patients undergoing the surgery across Canadian provinces.
Proteomic Analysis of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue Using Liquid Chromatography Tandem Mass Spectrometry

Objectives FFPE tissue is a standard method of specimen preservation for hospital pathology departments. Formalin-fixed paraffin-embedded tissue banks are a resource of histologically characterized specimens for retrospective biomarker investigation. We aim to establish liquid chromatography coupled with tandem mass spectrometry analysis of FFPE pancreatic tissue as a suitable strategy for the study of the pancreas proteome. Methods We investigated the proteomic profile of FFPE pancreatic tissue specimens, using liquid chromatography coupled with tandem mass spectrometry, from 9 archived specimens that were histologically classified as normal (n = 3), chronic pancreatitis (n = 3), and pancreatic cancer (n = 3). Results We identified 525 nonredundant proteins from 9 specimens. Implementing our filtering criteria, 78, 15, and 21 proteins were identified exclusively in normal, chronic pancreatitis, and pancreatic cancer specimens, respectively. Several proteins were identified exclusively in specimens with no pancreatic disease: spink 1, retinol dehydrogenase, and common pancreatic enzymes. Similarly, proteins were identified exclusively in chronic pancreatitis specimens: collagen &agr;1 (XIV), filamin A, collagen &agr;3 (VI), and SNC73. Proteins identified exclusively in pancreatic cancer included annexin 4A and fibronectin. Conclusions We report that differentially expressed proteins can be identified among FFPE tissue specimens originating from individuals with different pancreatic histologic findings. The mass spectrometry–based method used herein has the potential to enhance biomarker discovery and chronic pancreatitis research. Abbreviations CP - chronic pancreatitis, FFPE - formalin-fixed paraffin-embedded, GO - gene ontology, ID - inner diameter, KEGG - Kyoto Encyclopedia of Gene and Genomes, LC-MS/MS - liquid chromatography coupled with tandem mass spectrometry, LCM - laser capture microdissection, NP - normal pancreas, PC - pancreatic cancer
Snacking Patterns of Preschool-Aged Children: Opportunity for Improvement.

PURPOSE Dietary patterns established in childhood track into adulthood. Despite this, little research has explored preschoolers' snacking. This study examined snacking patterns (frequency, quality, quantity) of preschool-aged boys and girls. METHODS Cross-sectional data were collected on 52 children (23 males; 3.4 ± 1.1 years of age; BMI 16.1 ± 1.4 kg/m2) enrolled in the Guelph Family Health Study pilot. Parent-reported 3-day food records were analyzed for children's snacking patterns including frequency (number of snacking occasions per day), quantity (percent energy from snacks) and quality (inclusion of food groups from Eating Well with Canada's Food Guide, macronutrient distribution, sugary and salty snacks). Mann-Whitney U tests examined sex differences in snacking patterns. RESULTS Ninety-six percent of children snacked daily, consuming a mean of 2.3 ± 0.7 snacks per day. Snacks accounted for one-third of daily energy. 78% of boys' versus 63% of girls' snacks contained a food group (P = 0.016). Boys consumed significantly fewer sugary snacks (0.5 ± 0.4 vs 0.9 ± 0.6 snacks per day, P = 0.016), although the percent of snack calories from sugar for both boys and girls was high (group mean 37.2 ± 6.7%). CONCLUSIONS Nearly all preschoolers in this study snacked daily, and consumed a variety of snack foods. Boys' and girls' snacking preferences begin to diverge early in life. Preschool children should be encouraged to consume healthful snacks.
Thyroid Hormones Mediate Steroid-Independent Seasonal Changes in Luteinizing Hormone Pulsatility in the Ewe1

Abstract Thyroid hormones permit the increase in response to estradiol negative feedback in ewes at the transition to anestrus. In this study, we tested whether the thyroid hormones are also required for steroid-independent seasonal changes in pulsatile LH secretion. In experiment 1, Suffolk ewes were ovariectomized and thyroidectomized (THX) or ovariectomized only (controls) in late November. LH pulse frequency and amplitude were measured for 4 h in December, April, May, June, and August. Pulse frequency was also measured in the presence of estradiol-containing implants during the breeding (December) and early anestrus (March) seasons. As expected, in the presence of estradiol, pulse frequency declined between December and March in control but not THX ewes. In the absence of estradiol, a seasonal decline in frequency and an increase in amplitude occurred in control ewes, concurrent with lengthening photoperiod. A similar trend was seen in THX ewes, but the seasonal changes were lower in magnitude and not significant. In experiment 2, the same protocol was used (pulse measurements in December, May, and June) with a larger THX group size (n = 7). Results were similar to those of experiment 1 for controls. In THX ewes, pulse frequency did not change over time and was significantly elevated relative to that of controls during the summer. Pulse amplitude in THX ewes tended to increase during summer and did not differ from pulse amplitudes in control ewes. These results demonstrate that thyroid hormones are required for steroid-independent cycles in LH pulse frequency; however, some seasonal changes in amplitude still occur in the absence of thyroid hormones. This finding contrasts with the changes in estradiol negative feedback at the transition to anestrus, which are entirely thyroid hormone dependent.
Inter-comparison of Artificial Neural Network Algorithms for Time Series Forecasting: Predicting Indian Financial Markets

The financial market prediction is a specialized case of a time series analysis. Although many different methods have been employed by researchers for time series/financial data studies which include statistical techniques like ANOVA (analysis of variances), ARIMA (integrated moving averages), smoothing methods, correlation analysis etc., use of Artificial Neural Network (ANN) methods for financial prediction have become quite popular in the recent times. Though ANN methods like the conventionally used backpropagation method or the recurrent methods have been employed in the past, a complete and detailed investigation of more robust and popular ANN methods incorporated into ANN like the Resilient backprop, Marquardt Lavenberg, Conjugate gradient methods, One Step Secant, Quasi Newton methods, Bayesian learning etc., is missing from the literature. In the present study, a detailed study was undertaken to investigate the potential of these robust methods in the ANN domain for the Indian financial market prediction, more specifically the prediction of the share price of two popular scripts that are traded in the Indian secondary market. In this study, the 1 month ahead opening share price of two scripts namely ICICI bank and L&T have been forecasted. The results of our study
Brain‐derived neurotrophic factor prevents changes in Bcl‐2 family members and caspase‐3 activation induced by excitotoxicity in the striatum

Brain‐derived neurotrophic factor (BDNF) prevents the loss of striatal neurons caused by excitotoxicity. We examined whether these neuroprotective effects are mediated by changes in the regulation of Bcl‐2 family members. We first analyzed the involvement of the phosphatidylinositol 3‐kinase/Akt pathway in this regulation, showing a reduction in phosphorylated Akt (p‐Akt) levels after both quinolinate (QUIN, an NMDA receptor agonist) and kainate (KA, a non‐NMDA receptor agonist) intrastriatal injection. Our results also show that Bcl‐2, Bcl‐xL and Bax protein levels and heterodimerization are selectively regulated by NMDA and non‐NMDA receptor stimulation. Striatal cell death induced by QUIN is mediated by an increase in Bax and a decrease in Bcl‐2 protein levels, leading to reduced levels of Bax:Bcl‐2 heterodimers. In contrast, changes in Bax protein levels are not required for KA‐induced apoptotic cell death, but decreased levels of both Bax:Bcl‐2 and Bax:Bcl‐xL heterodimer levels are necessary. Furthermore, QUIN and KA injection activated caspase‐3. Intrastriatal grafting of a BDNF‐secreting cell line counter‐regulated p‐AKT, Bcl‐2, Bcl‐xL and Bax protein levels, prevented changes in the heterodimerization between Bax and pro‐survival proteins, and blocked caspase‐3 activation induced by excitotoxicity. These results provide a possible mechanism to explain the anti‐apoptotic effect of BDNF against to excitotoxicity in the striatum through the regulation of Bcl‐2 family members, which is probably mediated by Akt activation.
Antithrombin III concentrate to treat heparin resistance in patients undergoing cardiac surgery.

OBJECTIVE The purpose of this report is to describe the clinical use of antithrombin III concentrate in 53 patients who were found, in the operating room before cardiopulmonary bypass, to be heparin resistant. METHOD Resistance to heparin was determined to be present when greater than 600 U/kg body weight of heparin failed to prolong the kaolin-activated clotting time to more than 600 seconds in 53 aprotinin-treated patients. Blood samples were obtained for subsequent antithrombin III activity determination. Patients were then administered 500 U of antithrombin III concentrate, and the activated clotting time was remeasured. If the activated clotting time remained less than 600 seconds, a second 500-U dose was given. RESULTS Of the 53 patients, 45 (85%) had subnormal measured antithrombin III activity, and the mean plasma antithrombin III activity level for the entire group was 67% (normal 80%-120%). Administration of antithrombin III concentrate (500 U in 45 patients and 1000 U in 8 patients) resulted in prolongation of the mean activated clotting time from 492 to 789 seconds without additional heparin. The mean heparin dose response increased from 36.5 to 69.3 s x U(-1) x mL(-1) with antithrombin III treatment. Only one patient did not achieve the target activated clotting time, despite administration of greater than 600 U/kg heparin and 1000 U of antithrombin III concentrate, and was treated with fresh-frozen plasma. CONCLUSIONS On the basis of the criterion used in this report, most of the patients defined as being heparin resistant had subnormal plasma antithrombin III activity. Treatment with antithrombin III concentrate resulted in potentiation of the heparin effect to meet predetermined activated clotting time thresholds and allow for cardiopulmonary bypass.