Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of a repressor and its binding sites for regulation of the Bacillus subtilis iol divergon.

Transcription of the Bacillus subtilis iol divergon is negatively regulated by a repressor encoded by iolR, which belongs to the DeoR family of bacterial regulators. Gel retardation analysis involving the IolR protein synthesized in Escherichia coli revealed that IolR bound specifically and independently to each of the iol and iolRS promoter regions, with higher affinity to iol. DNase I footprinting revealed that IolR affected DNase I sensitivity either in the iol promoter region between nucleotides -46 and +51 or in iolRS between -79 and -2 (+1 is the transcription initiation nucleotide of both iol and iolRS), indicating its interaction with the extended regions of the iol and iolRS promoters. Deletion analysis indicated that the iol region between -23 and +21 is involved mainly in IolR binding and negative regulation, while the iolRS region between -70 and -44 comprises at least part of the cis-acting sequences for IolR binding and negative regulation. Sequence examination of the extended regions revealed that a tandem direct repeat consisting of two relatively conserved 11-mer sequences, WRAYCAADARD (where D is A, G or T; R is A or G; W is A or T; and Y is C or T), found in each of the iol and iolRS regions might be a determinant sequence for the IolR-DNA interaction. Actual involvement of the direct repeats in the IolR-DNA interaction was shown by the deficiency of IolR-binding and negative regulation that was caused by substitution of the conserved bases within the conserved sequences. These results imply a unique mode of interaction of IolR with the target DNA.
Can Internet-based education improve physician confidence in dealing with domestic violence?

BACKGROUND AND OBJECTIVES Domestic violence (DV) is a common, under-recognized source of visits to health care professionals. Even when recognized, physicians are reluctant to deal with DV, citing a lack of education and lack of confidence in addressing issues presented by DV patients. Only a small number of DV education programs have been shown to lead to improvements in professional knowledge and confidence, and these are intensive, multi-day courses. We sought to develop an on-line DV education program that could achieve improvements in physician confidence and attitudes in managing DV patients comparable to classroom-based courses. METHODS We created an interactive, case-based DV education program targeted to physicians caring for DV patients. We tested the effectiveness of this program in changing attitudes and beliefs in a randomized, controlled trial of Kansas physicians who volunteered to participate in a study of on-line continuing medical education. We measured program effectiveness with an externally developed and validated pretest/posttest instrument. RESULTS Sixty-five physicians completed the pretest/posttest, 28 of whom were assigned to receive the on-line DV program. We found a +17.8% mean change in confidence (self efficacy) for physicians who took the DV program versus a -. 6% change for physicians who did not take the program. We also found improvements in other important areas associated with poor management of DV patients. These changes were similar or greater in magnitude to those reported by others who have used the same survey tool to evaluate an intensive, multi-hour classroom approach to DV education. User satisfaction with the on-line program was high. CONCLUSIONS An interactive, case-based, on-line DV education program that teaches problem-solving skills improves physician confidence and beliefs in managing DV patients as effectively as an intensive classroom-based approach. Such programs may be of benefit to those seeking to improve their personal skills or their health care delivery system's response to DV.
Long chain W3 polyunsaturated fatty acids and lipid pattern in the mother and the newborn infant

We studied 162 mother-neonate pairs to determine the relationship between w3 long chain polyunsaturated fatty acid (w3LCP) intake during pregnancy and their levels in the mother and the neonate, and the general lipid pattern in the mother and the neonate. A dietetic interview was performed to assess the w3LCP intake during pregnancy. In both mothers and neonates we studied the w3LCPs in plasma and erythrocyte phospholipids and also the general lipid profile (total cholesterol, HDL-c, LDL-c, triglycerides, apo A1 and apo B). The w3LCP intake assessed by the dietetic interview (0.74 +/- 0.52 g/day) did not correlated with any of the parameters of the general lipid pattern in mothers or neonates. In mothers, the w3LCP levels in plasma expressed in percentages showed a positive correlation with apo A1 and HDL-c, and a negative correlation with triglycerides and apo B. The w3LCPs levels in mothers showed an inconsistent and weak correlation with triglycerides and apo B in neonates. When w3LCPs levels were assessed in the neonates themselves a consistent positive correlation was found with triglycerides. We concluded that in the dietetic range of our population, the intake of w3LCPs was not associated to any changes in the general lipid pattern of mothers or neonates. Whereas the w3LCP levels in mothers were correlated with the changes in the general lipid pattern reported outside pregnancy, such correlations were not present in regard to the neonate general profile, whereas the newborn's w3LCP levels were correlated with triglycerides. We believe that the hypertriglyceridemia of pregnancy, the placenta and the peculiarities of fetal metabolism are the causes of the aforementioned findings.
Site-directed mutagenesis, fluorescence, and two-dimensional NMR studies on microenvironments of effector region aromatic residues of human c-Ha-Ras protein.

The Tyr residues in positions 32 and 40 of human c-Ha-Ras protein were replaced by site-directed mutagenesis (Y32F, Y32W, Y40K, and Y40W) to examine their roles in the signal-transducing activity and the sensitivity to the GTPase activating protein (GAP). The signal-transducing activity of the oncogenic Ras protein in PC12 cells was lost upon mutations Y32F and Y40K, but retained upon mutations Y32W and Y40W. These results suggest that residues 32 and 40 are both required to have aromatic groups and residue 32 is further required to have a hydrogen donor. On the other hand, three mutations (Y32F, Y32W, and Y40W) caused no appreciable reduction in either GAP-binding affinity or GAP sensitivity. By the Y40K mutation, GAP-binding affinity was slightly lowered, while GAP sensitivity was drastically impaired. Therefore, for residues 32 and 40 of Ras, interactions with GAP appear to be different from those with the target of signal transduction in the PC12 cell. As for the Y32W-Ras protein bound with an unhydrolyzable GTP analogue (GMPPNP), the Trp32 fluorescence is appreciably red-shifted, weaker, and more susceptible to KI quenching as compared to that of the GDP-bound form. Two-dimensional NMR spectroscopy with selectively deuterated Ras proteins revealed fewer and weaker nuclear Overhauser effects on the aromatic protons of Trp32 in the GMPPNP-bound form than in the GDP-bound form. This indicates that the side chain of Trp32 is more exposed to the solvent in the GMPPNP-bound form than in the GDP-bound form. (ABSTRACT TRUNCATED AT 250 WORDS)
Relevance of Routine Use of the Anaerobic Blood Culture Bottle

ABSTRACT Using the BacT/Alert automated system, we conducted a 1-year retrospective study on blood cultures, focusing on the relevance of routine use of the anaerobic bottle. The rate of patients with positive blood cultures was 19.7%. Among these, 13.5% had a positive anaerobic bottle in the absence of any aerobic bottle, and 2/3 of these grew with nonobligate anaerobes. These patients were hospitalized in 20 out of 26 wards of the hospital group. For 65.4% of the monomicrobial-positive blood cultures growing Enterobacteriaceae, the anaerobic bottle detected growth earlier than the corresponding aerobic bottle. These data suggest that, in our institution, the use of an anaerobic bottle is still relevant.
Reduced Mortality Rate Associated with Annual Mammograms after Breast Cancer Therapy

Abstract: Guidelines have been developed for appropriate posttherapy surveillance for breast cancer recurrence. One purpose of posttherapy surveillance is to detect potentially curable local recurrences and new cancers in the opposite breast. The objective of this investigation was to assess the impact of annual mammography on all‐cause mortality in breast cancer survivors. We conducted a case–control analysis nested in a cohort of 865 stage I or II breast cancer patients diagnosed from 1996 to 1999. The exposure variable was the number of mammograms received after completing primary therapy. Cases were decedents and we used risk‐set sampling to match eight controls to each case on follow‐up time. The mortality rate declined with an increasing number of mammograms (p for trend = 0.007). The age‐ and therapy‐adjusted odds ratio associating receipt of an additional mammogram, compared with receipt of no mammogram, equaled 0.77 (95% confidence interval [CI] 0.53–1.1). These results are consistent with a protective effect of regular surveillance mammography after completing therapy for early stage breast cancer.
trp RNA-Binding Attenuation Protein-5′ Stem-Loop RNA Interaction Is Required for Proper Transcription Attenuation Control of the Bacillus subtilis trpEDCFBAOperon

ABSTRACT The trp RNA-binding attenuation protein (TRAP) regulates expression of the Bacillus subtilis trpEDCFBAoperon by a novel transcription attenuation mechanism. Tryptophan-activated TRAP binds to the nascent trp leader transcript by interacting with 11 (G/U)AG repeats, 6 of which are present in an antiterminator structure. TRAP binding to these repeats prevents formation of the antiterminator, thereby promoting formation of an overlapping intrinsic terminator. A third stem-loop structure that forms at the extreme 5′ end of the trp leader transcript also plays a role in the transcription attenuation mechanism. The 5′ stem-loop increases the affinity of TRAP fortrp leader RNA. Results from RNA structure mapping experiments demonstrate that the 5′ stem-loop consists of a 3-bp lower stem, a 5-by-2 asymmetric internal loop, a 6-bp upper stem, and a hexaloop at the apex of the structure. Footprinting results indicate that TRAP interacts with the 5′ stem-loop and that this interaction differs depending on the number of downstream (G/U)AG repeats present in the transcript. Expression studies with trpE′-′lacZtranslational fusions demonstrate that TRAP-5′ stem-loop interaction is required for proper regulation of the trp operon. 3′ RNA boundary experiments indicate that the 5′ structure reduces the number of (G/U)AG repeats required for stable TRAP-trp leader RNA association. Thus, TRAP-5′ stem-loop interaction may increase the likelihood that TRAP will bind to the (G/U)AG repeats in time to block antiterminator formation.
Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat

1 Perturbations of arterial blood pressure change medullary raphe neurone activity and the respiratory motor pattern. This study sought evidence for actions of baroresponsive raphe neurones on the medullary respiratory network. 2 Blood pressure was perturbed by intravenous injection of an α1‐adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in thirty‐six Dial‐urethane‐anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus‐nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla. Data were analysed with cycle‐triggered histograms, peristimulus time and cumulative sum histograms, cross‐correlograms and spike‐triggered averages of efferent phrenic nerve activity. 3 Prolongation of the expiratory phase and decreased peak integrated phrenic amplitude were most frequently observed. Of 707 neurones studied, 310 had altered firing rates during stimulation; changes in opposite directions were monitored simultaneously in fifty‐six of eighty‐seven data sets with at least two baroresponsive neurones. 4 Short time scale correlations were detected between neurones in 347 of 3388 pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant offset correlogram features indicative of paucisynaptic interactions. In correlated raphe‐ventrolateral medullary neurone pairs with at least one baroresponsive neurone, six of seven ventrolateral medullary decrementing expiratory (E‐Decr) neurones increased their firing rate during baroreceptor stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones correlated with raphe cells decreased their firing rate during baroreceptor stimulation. 5 The results support the hypothesis that raphe neuronal assemblies transform and transmit information from baroreceptors to neurones in the ventral respiratory group. The inferred actions both limit and promote responses to sensory perturbations and match predictions from simulations of the respiratory network.
Major histocompatibility complex similarity and sexual selection: different does not always mean attractive

Females that mate multiply have the possibility to exert postcopulatory choice and select more compatible sperm to fertilize eggs. Prior work suggests that dissimilarity in major histocompatibility complex (MHC) plays an important role in determining genetic compatibility between partners. Favouring a partner with dissimilar MHC alleles would result in offspring with high MHC diversity and therefore with enhanced survival thanks to increased resistance to pathogens and parasites. The high variability of MHC genes may further allow discrimination against the sperm from related males, reducing offspring homozygosity and inbreeding risk. Despite the large body of work conducted at precopulatory level, the role of MHC similarity between partners at postcopulatory level has been rarely investigated. We used an internal fertilizing fish with high level of multiple matings (Poecilia reticulata) to study whether MHC similarity plays a role in determining the outcome of fertilization when sperm from two males compete for the same set of eggs. We also controlled for genomewide similarity by determining similarity at 10 microsatellite loci. Contrary to prediction, we found that the more MHC‐similar male sired more offspring while similarity at the microsatellite loci did not predict the outcome of sperm competition. Our results suggest that MHC discrimination may be involved in avoidance of hybridization or outbreeding rather than inbreeding avoidance. This, coupled with similar findings in salmon, suggests that the preference for MHC‐dissimilar mates is far from being unanimous and that pre‐ and postcopulatory episodes of sexual selection can indeed act in opposite directions.
Sepsis-induced brain dysfunction

Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood–brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke’s encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood–brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.
The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape.

Chilling and freezing can reduce significantly vine survival and fruit set in Vitis vinifera wine grape. To overcome such production losses, a recently identified grapevine C-repeat binding factor (CBF) gene, VvCBF4, was overexpressed in grape vine cv. 'Freedom' and found to improve freezing survival and reduced freezing-induced electrolyte leakage by up to 2 °C in non-cold-acclimated vines. In addition, overexpression of this transgene caused a reduced growth phenotype similar to that observed for CBF overexpression in Arabidopsis and other species. Both freezing tolerance and reduced growth phenotypes were manifested in a transgene dose-dependent manner. To understand the mechanistic basis of VvCBF4 transgene action, one transgenic line (9-12) was genotyped using microarray-based mRNA expression profiling. Forty-seven and 12 genes were identified in unstressed transgenic shoots with either a >1.5-fold increase or decrease in mRNA abundance, respectively. Comparison of mRNA changes with characterized CBF regulons in woody and herbaceous species revealed partial overlaps, suggesting that CBF-mediated cold acclimation responses are widely conserved. Putative VvCBF4-regulon targets included genes with functions in cell wall structure, lipid metabolism, epicuticular wax formation and stress-responses suggesting that the observed cold tolerance and dwarf phenotypes are the result of a complex network of diverse functional determinants.
PPARα regulates mobilization and homing of endothelial progenitor cells through the HIF-1α/SDF-1 pathway.

PURPOSE The mechanism for the antiangiogenic activity of peroxisome proliferator-activated receptor alpha (PPARα) remains incompletely understood. Endothelial progenitor cells (EPC) are known to participate in neovascularization (NV). The purpose of this study was to investigate whether PPARα regulates EPC during retinal NV. METHODS Retinal NV was induced by oxygen-induced retinopathy (OIR). Mice with OIR were injected intraperitoneally with the PPARα agonist fenofibric acid (FA) or with adenovirus expressing PPARα (Ad-PPARα). Flow cytometry was used to quantify circulating and retinal EPC. Serum stromal cell-derived factor 1 (SDF-1) levels were measured by ELISA. Hypoxia was induced in primary human retinal capillary endothelial cells (HRCEC) and mouse brain endothelial cells (MBEC) by CoCl2. Levels of SDF-1 and hypoxia-inducible factor 1 alpha (HIF-1α) were measured by Western blotting. RESULTS Fenofibric acid and overexpression of PPARα attenuated the increase of circulating and retinal EPC, correlating with suppressed retinal NV in OIR mice at P17. The PPARα knockout enhanced the OIR-induced increase of circulating and retinal EPC. Fenofibric acid decreased retinal HIF-1α and SDF-1 levels as well as serum SDF-1 levels in the OIR model. In HRCEC, PPARα inhibited HIF-1α nuclear translocation and SDF-1 overexpression induced by hypoxia. Further, MBEC from PPARα(-/-) mice showed more prominent activation of HIF-1α and overexpression of SDF-1 induced by hypoxia, compared with the wild-type (WT) MBEC. PPARα failed to block SDF-1 overexpression induced by a constitutively active mutant of HIF-1α, suggesting that regulation of SDF-1 by PPARα was through blockade of HIF-1α activation. CONCLUSIONS Peroxisome proliferator-activated receptor alpha suppresses ischemia-induced EPC mobilization and homing through inhibition of the HIF-1α/SDF-1 pathway. This represents a novel molecular mechanism for PPARα's antiangiogenic effects.
Education Inequality: an Examination of the Political and Economic Factors Associated with Educational Disparities Around the World

Torpey-Saboe, Nichole (Ph.D., Political Science) Education Inequality: An examination of the political and economic factors associated with educational disparities around the world Thesis directed by Professor David S. Brown Education is broadly recognized as a human right and is critical to the achievement of other individual and social goods. Yet despite widespread recognition of the importance of education, access is still very uneven. In some countries, education is available to all on a fairly equal basis, while in others, only the elite are educated. What explains this variation? While much attention has been paid to income inequality, education inequality is less understood. Drawing from theories on human capital and income inequality, I hypothesize that education inequality is shaped by the forces of modernization, globalization, and democratization. I construct a new measure of education inequality and test my hypotheses using time-series cross-national data. I also analyze the case of Mexico, using original survey data. Finally, I look at disparities in quality of education. I nd that the relationship between modernization, democratization, globalization, and education inequality is complex. Globalization is only related to declining education inequality for labor abundant countries. For capital abundant countries, globalization is associated with increased education inequality. This extends the classic Heckscher-Ohlin model beyond the realm of income. These ndings
The association between socioeconomic status and survival among children with Hodgkin and non‐Hodgkin lymphomas in a universal health care system

The association between socioeconomic status (SES) and cancer survival has been studied extensively in adults. However, little is known about this relationship in the pediatric population, specifically in jurisdictions with universal health care insurance programs. Our aim was to determine whether lower SES is associated with poorer survival in pediatric Hodgkin (HL) and non‐Hodgkin lymphoma (NHL) patients in Ontario.
Increased Susceptibility of Low-Density Lipoprotein to Ex Vivo Oxidation in Mice Transgenic for Human Apolipoprotein B Treated with 1 Melatonin-Related Compound Is Not Associated with Atherosclerosis Progression

Considerable evidence supports the hypothesis that LDL oxidation has an important role in atherosclerosis. It has been demonstrated that the feeding of hypercholesterolemic mice on an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in aorta and the sensitivity of atherogenic lipoprotein to ex vivo oxidation even though high melatonin doses inhibit lipoprotein oxidation in vitro. A melatonin-related compound (DTBHB: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3,5-di-tert-butyl-4-hydroxybenzamide) has been reported to strongly inhibit lipid peroxidation in vitro. In the present study, DTBHB treatment considerably increased the sensitivity of atherogenic lipoproteins to ex vivo oxidation but did not modify atherosclerotic lesion development in mice. Moreover, DTBHB treatment did not induce detectable lipidic alteration. These data confirm that the capacity of molecules to inhibit atherogenic lipoprotein oxidation in vitro offers no prediction of their capacity to inhibit in vivo atherosclerosis development.