Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Estrogens and Endocrine-Disrupting Chemicals on Cell Differentiation–Survival–Proliferation in Brain: Contributions of Neuronal Cell Lines

Estrogens and estrogen receptors (ER) are key actors in the control of differentiation and survival and act on extrareproductive tissues such as brain. Thus, estrogens may display neuritogenic effects during development and neuroprotective effects in the pathophysiological context of brain ischemia and neurodegenerative pathologies like Alzheimer's disease or Parkinson's disease. Some of these effects require classical transcriptional “genomic” mechanisms through ER, whereas other effects appear to rely clearly on “membrane-initiated mechanisms” through cytoplasmic signal transduction pathways. Disturbances of these mechanisms by endocrine-disrupting chemicals (EDC) may exert adverse effects on brain. Some EDC may act via ER-independent mechanisms but might cross-react with endogenous estrogen. Other EDC may act through ER-dependent mechanisms and display agonistic/antagonistic estrogenic properties. Because of these potential effects of EDC, it is necessary to establish sensitive cell-based assays to determine EDC effects on brain. In the present review, some effects of estrogens and EDC are described with focus on ER-mediated effects in neuronal cells. Particular attention is given to PC12 cells, an interesting model to study the mechanisms underlying ER-mediated differentiating and neuroprotective effects of estrogens.
Cotransformation and gene targeting in mouse embryonic stem cells

We have investigated cotransformation in mammalian cells and its potential for identifying cells that have been modified by gene targeting. Selectable genes on separate DNA fragments were simultaneously introduced into cells by coelectroporation. When the introduced fragments were scored for random integration, 75% of the transformed cells integrated both fragments within the genome of the same cell. When one of the cointroduced fragments was scored for integration at a specific locus by gene targeting, only 4% of the targeted cells cointegrated the second fragment. Apparently, cells that have been modified by gene targeting with one DNA fragment rarely incorporate a second DNA fragment. Despite this limitation, we were able to use the cotransformation protocol to identify targeted cells by screening populations of colonies that had been transformed with a cointroduced selectable gene. When hypoxanthine phosphoribosyltransferase (hprt) targeting DNA was coelectroporated with a selectable neomycin phosphotransferase (neo) gene into embryonic stem (ES) cells, hprt-targeted colonies were isolated from the population of neo transformants at a frequency of 1 per 70 G418-resistant colonies. In parallel experiments with the same targeting construct, hprt-targeted cells were found at a frequency of 1 per 5,500 nonselected colonies. Thus, an 80-fold enrichment for targeted cells was observed within the population of colonies transformed with the cointroduced DNA compared with the population of nonselected colonies. This enrichment for targeted cells after cotransformation should be useful in the isolation of colonies that contain targeted but nonselectable gene alterations.
Multiobjective Design of Linear Antenna Arrays Using Bayesian Inference Framework

The Bayesian inference framework for design introduced in Chan and Goggans [“Using Bayesian inference for linear antenna array design,” IEEE Trans. Antennas Propag. , vol. 59, no. 9, pp. 3211-3217, Sep. 2011] is applied to design linear antenna arrays capable of realizing multiple radiation patterns while satisfying various design requirements. Many design issues are involved when designing a linear antenna array. This paper focuses on four practical design issues: the need for minimum spacing between two adjacent array elements, limitations in the dynamic range and accuracy of the current amplitudes and phases, the ability to produce multiple desired radiation patterns using a single array, and the ability to maintain a desired radiation pattern over a certain frequency band. We present an implementation of these practical design requirements based on the Bayesian inference framework, together with representative examples. Our results demonstrate the capability and robustness of the Bayesian method in incorporating real-world design requirements into the design of linear antenna arrays.
Gonadotropin secretion in ovariectomized Chinese Meishan and hybrid large white gilts; responses to challenges with estradiol benzoate, gonadotropin-releasing hormone, or porcine follicular fluid.

Castrated Meishan (MS) and hybrid Large White (hLW) gilts were used in a series of challenge experiments to establish differences in the control of gonadotropin secretion. Acutely ovariectomized gilts (72 h) were injected i.m. with 10 micrograms/kg estradiol benzoate (EB) and serially bled for evaluation of estradiol clearance from the blood and patterns of LH and FSH release. Estradiol was more rapidly metabolized from the circulatory system of the acutely ovariectomized MS gilts than from the hLW gilts; as a consequence, hLW gilts had higher concentrations of estradiol than MS gilts at 24-32 h (p < 0.05) and 48-60 h (p < 0.01) post-EB treatment. The hLW but not the MS gilts exhibited a classic negative/positive LH response to EB; MS gilts responded with a random release of large episodes of LH. Plasma FSH concentrations were consistently greater (p < 0.05) in acutely ovariectomized MS gilts than in hLW gilts. Both breeds demonstrated a slight negative FSH response to EB and then exhibited increased variability in plasma FSH with time after treatment. Mean plasma LH was immediately elevated in chronically ovariectomized (> 14 days) hLW and MS gilts given 1 microgram/kg of GnRH i.m. , but the magnitude of the LH response was greater (p < 0.01) in the hLW gilts. Comparable differences (p < 0.01) in FSH secretion were also observed, indicating the presence of greater pools of releasable FSH and LH in the hLW gilts, or a greater sensitivity to GnRH. (ABSTRACT TRUNCATED AT 250 WORDS)
Utilization of Splicing Elements and Polyadenylation Signal Elements in the Coupling of Polyadenylation and Last-Intron Removal

ABSTRACT Polyadenylation (PA) is the process by which the 3′ ends of most mammalian mRNAs are formed. In nature, PA is highly coordinated, or coupled, with splicing. In mammalian systems, the most compelling mechanistic model for coupling arises from data supporting exon definition (2, 34, 37). We have examined the roles of individual functional components of splicing and PA signals in the coupling process by using an in vitro splicing and PA reaction with a synthetic pre-mRNA substrate containing an adenovirus splicing cassette and the simian virus 40 late PA signal. The effects of individually mutating splicing elements and PA elements in this substrate were determined. We found that mutation of the polypyrimidine tract and the 3′ splice site significantly reduced PA efficiency and that mutation of the AAUAAA and the downstream elements of the PA signal decreased splicing efficiency, suggesting that these elements are the most significant for the coupling of splicing and PA. Although mutation of the upstream elements (USEs) of the PA signal dramatically decreased PA, splicing was only modestly affected, suggesting that USEs modestly affect coupling. Mutation of the 5′ splice site in the presence of a viable polypyrimidine tract and the 3′ splice site had no effect on PA, suggesting no effect of this element on coupling. However, our data also suggest that a site for U1 snRNP binding (e.g., a 5′ splice site) within the last exon can negatively effect both PA and splicing; hence, a 5′ splice site-like sequence in this position appears to be a modulator of coupling. In addition, we show that the RNA-protein complex formed to define an exon may inhibit processing if the definition of an adjacent exon fails. This finding indicates a mechanism for monitoring the appropriate definition of exons and for allowing only pre-mRNAs with successfully defined exons to be processed.
In vitro efficacy of some indigenous plants on the inhibition of development of eggs of Ascaridia galli (Digenia: Nematoda)

In vitro efficacy of five indigenous plants namely Bishkatali ( Polygonum hydropiper ), Neem ( Azadirachta indica ), Papaya ( Carica papaya ), Korolla ( Momordica charantia ) and Mahogany ( Swietenia macrophylla ) were studied against the development of Ascaridia galli eggs from July 2007 to May 2008. Fresh juice, extracts and dust of leaves were tested. Fresh juice of leaves were trialed at 5%, 10% and 20% concentrations; aqueous, ethanol and methanol extracts were used at 1%, 2% and 4% concentrations and dusts of leaves were applied at 10% and 20% concentration. Among the trials, 4% of methanol extracts of papaya showed the highest efficacy (92.86%) followed by 4% ethanol extract of papaya (92%). Among the selected plants and in all three concentrations of fresh juice of leave, Bishkatali (88.46% at 20% conc.) was the highest effective plant against the development of A. galli eggs. Papaya showed the highest efficacy (71.42%) in 1% aqueous solution, but bishkatali was found as the best (73.33% and 83.33% respectively) in 2% and 4% concentration of ethanol extract of the five selected plants. In vitro screening of 5 plants with ethanol extract revealed that papaya was the highest efficacious plant (92% at 4% conc.) against development of A. galli eggs. Among the plants, in all concentrations of methanol extract of leaves, papaya was observed as best plant (92.86%, 88% and 78.95% at 4%, 2% and 1% of conc. respectively) followed by bishkatali (80% and 75% at 4% and 2% of conc. respectively) and neem (78.57% and 73.08% at 4% and 2% conc. respectively). In two concentrations of dust of leaves, bishkatali was observed as the effective plant (75% at 20% and 73.33% at 10% conc.) among the five plants. The present study suggests that dust of bishkatali leaves can be used with litter for inhibition of development of A. galli eggs and fresh juice and extract of bishkatali, neem and papaya may be impregnated in litter and used after sun dry. Key words: In vitro efficacy, indigenous plants, development, Ascaridia galli eggs doi: 10.3329/bjvm.v6i2. 2329 Bangl. J. Vet. Med. (2008). 6 (2): 159-167 Â Â
Peer review at the American Journal of Roentgenology: how reviewer and manuscript characteristics affected editorial decisions on 196 major papers.

OBJECTIVE The objective of this study was to examine the relative influence of manuscript characteristics and peer-reviewer attributes in the assessment of manuscripts. MATERIALS AND METHODS Over a 6-month period, all major papers submitted to the American Journal of Roentgenology (AJR) were entered into a database that recorded manuscript characteristics, demographic profiles of reviewers, and the disposition of the manuscript. Manuscript characteristics included reviewer ratings on five scales (rhetoric, structure, science, import, and overall recommendation); the subspecialty class of the paper; the primary imaging technique; and the country of origin. Demographic profiles of the reviewers included age, sex, subspecialty, years of reviewing, academic rank, and practice type. Statistical analysis included correlation analysis, ordinal logistic regression, and analysis of variance. RESULTS A total of 445 reviews of 196 manuscripts were the work of 335 reviewers. Of the 196 submitted manuscripts, 20 (10.2%) were accepted, 106 (54.1%) were rejected, and 70 (35.7%) were rejected with the opportunity to resubmit. Regarding manuscript characteristics, we found that the country of origin, score on the science scale, and score on the import scale were statistically significant variables for predicting the final disposition of a manuscript. Of the reviewer attributes, we found a statistically significant association between greater reviewer age and also higher academic rank with lower scores on the import scale. Reviewer concordance was higher for structure, science, and overall scores than on the rhetoric and import scores. Greater variability in the overall scoring of papers could be attributed to the reviewer than the manuscript, but both factors combined explain only 23% of the total variability. CONCLUSION At the AJR, manuscript acceptance was most strongly associated with reviewer scoring of the science and import of a major paper and also with the country of origin. Reviewers who were older and of higher academic rank tended to discount the importance of manuscripts.
Tolerability of isradipine in early Parkinson's disease: A pilot dose escalation study

Recent data suggests that isradipine, a dihydropyridine calcium channel blocker, is neuroprotective in preclinical models of parkinsonism. Isradipine has not been systematically studied in patients with Parkinson's disease (PD). The aim of this study was to evaluate safety and tolerability of isradipine controlled release (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty‐one percent of subjects completed the study. Tolerability of isradipine CR was dose dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg. Isradipine had no significant effect on blood pressure or PD motor disability. The two most common reasons for dose reduction were leg edema (7) and dizziness (3). There was no difference in isradipine tolerability between subjects with and without dopaminergic treatment, or with and without hypertension. © 2010 Movement Disorder Society
The Relationship between Body Mass Index and the Severity of Coronary Artery Disease in Patients Referred for Coronary Angiography

Background and Aim. Obesity is associated with an increased risk of cardiovascular disease and may be associated with more severe coronary artery disease (CAD); however, the relationship between body mass index [BMI (kg/m2)] and CAD severity is uncertain and debatable. The aim of this study was to examine the relationship between BMI and angiographic severity of CAD. Methods. Duke Jeopardy Score (DJS), a prognostic tool predictive of 1-year mortality in CAD, was assigned to angiographic data of patients ≥18 years of age (N = 8,079). Patients were grouped into 3 BMI categories: normal (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2); and multivariable adjusted hazard ratios for 1-year all-cause and cardiac-specific mortality were calculated. Results. Cardiac risk factor prevalence (e.g., diabetes, hypertension, and hyperlipidemia) significantly increased with increasing BMI. Unadjusted all-cause and cardiac-specific 1-year mortality tended to rise with incremental increases in DJS, with the exception of DJS 6 (p < 0.001). After adjusting for potential confounders, no significant association of BMI and all-cause (HR 0.70, 95% CI .48–1.02) or cardiac-specific (HR 1.11, 95% CI .64–1.92) mortality was found. Conclusions. This study failed to detect an association of BMI with 1-year all-cause or cardiac-specific mortality after adjustment for potential confounding variables.
Age and metallicity gradients in early-type galaxies: A dwarf to giant sequence

We studied the stellar populations of 40 early-type galaxies using medium-resolution long-slit spectroscopy along their major axes (and along the minor axis for two of them). The sample, including elliptical and lenticular galaxies as well as dwarf galaxies, is combined with other previously published data in order to discuss the systematics of the radial gradients of age and metallicity over a large mass range, from 10(7)M(circle dot) to 10(12)M(circle dot) (-9.2 > M-B > -22.4 mag). The well-known mass-metallicity relation is continuous throughout the whole mass range, in the sense that more massive galaxies are more metal-rich. The age-mass relation is consistent with the idea of downsizing: smaller galaxies have more extended star formation histories than more massive ones. The transition-type dwarfs (intermediate between dwarf irregular and dwarf elliptical galaxies) deviate from this relation having younger mean age, and the low-mass dwarf spheroidals have older ages, marking a discontinuity in the relation, possibly due to selection effects. In all mass regimes, the mean metallicity gradients are approximately -0.2 and the mean age gradients + 0.1 dex per decade of radius. The individual gradients are widely spread: -0.1 < del(Age) < 0.4 and -0.54 <del([Fe/H]) < + 0.2. We do not find evidence for a correlation between the metallicity gradient and luminosity, velocity dispersion, central age or age gradient. Likewise, we do not find a correlation between the age gradient and any other parameter in bright early-type galaxies. In faint early-types with M-B greater than or similar to -17 mag, on the other hand, we find a strong correlation between the age gradient and luminosity: the age gradient becomes more positive for fainter galaxies. Together with the observed downsizing phenomenon this indicates that, as time passes, star formation persists in dwarf galaxies and becomes more centrally concentrated. However, this prolonged central star formation is not reflected in the metallicity profiles of the dwarfs in our sample. We conclude that various physical mechanisms can lead to similar gradients and that these gradients are robust against the environmental effects. In particular, the gradients observed in dwarf galaxies certainly survived the transformation of the progenitors through tidal harassment or/and ram-pressure stripping. The diversity of metallicity gradients amongst dwarf elliptical galaxies may reflect a plurality of progenitors' morphologies. The dwarfs with steep metallicity gradients could have originated from blue compact dwarfs and those with flat profiles from dwarf irregulars and late-type spirals.
Diverse associations of 25‐hydroxyvitamin D and 1,25‐dihydroxy‐vitamin D with dyslipidaemias

Abstract. Karhapää P, Pihlajamäki J, Pörsti I, Kastarinen M, Mustonen J, Niemelä O, Kuusisto J (University of Eastern Finland, Kuopio; University of Tampere, Tampere; and Laboratory and Medical Research Unit, University of Tampere, Tampere; Finland). Diverse associations of 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D with dyslipidaemias. J Intern Med 2010; 268: 604–610.
Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA

Resisting Repeats A set of diseases, including myotonic dystrophy, are caused by the expansion of a simple repeat in genomic DNA, which, when transcribed into RNA, can be toxic to other cellular processes. Ameliorating the effects of this toxic, repeat-laden RNA may also relieve the symptoms of the disease. Wheeler et al. (p. 336; see the Perspective by Cooper) developed an antisense morpholino oligonucleotide complementary to the expanded repeats found in the myotonic dystrophy protein kinase messenger RNA (mRNA). The morpholino bound the repeats in vitro and displaced the inappropriately bound and sequestered RNA splicing factor, Muscleblind-like 1. In an in vivo mouse model for myotonic dystrophy, local injection of the morpholino corrected a number of cellular defects in muscle, including the alternative mRNA splicing of several genes, among them the muscle-specific chloride channel, CIC1, leading to a marked reduction in the myotonia. An antisense oligonucleotide ameliorates the symptoms of myotonic dystrophy in transgenic mice. Genomic expansions of simple tandem repeats can give rise to toxic RNAs that contain expanded repeats. In myotonic dystrophy, the expression of expanded CUG repeats (CUGexp) causes abnormal regulation of alternative splicing and neuromuscular dysfunction. We used a transgenic mouse model to show that derangements of myotonic dystrophy are reversed by a morpholino antisense oligonucleotide, CAG25, that binds to CUGexp RNA and blocks its interaction with muscleblind-like 1 (MBNL1), a CUGexp-binding protein. CAG25 disperses nuclear foci of CUGexp RNA and reduces the overall burden of this toxic RNA. As MBNL1 is released from sequestration, the defect of alternative splicing regulation is corrected, thereby restoring ion channel function. These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs.
Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey

ABSTRACT Objective: To determine diurnal variability of symptoms in chronic obstructive pulmonary disease (COPD) and to assess the impact of COPD upon patients’ morning activities and routines. Research design and methods: Quantitative internet interviews with 803 COPD patients from Europe and the USA, including 289 patients with severe COPD. Severe COPD was defined according to regular use of COPD medication, third level of breathlessness or above using the modified Medical Research Council (MRC) dyspnoea scale (MRC dyspnoea score ≥3) and one or more COPD exacerbations in the preceding 12 months. Results: Morning was the worst time of day for COPD symptoms, particularly in patients with severe COPD (reported by 46% of severe patients). In these patients, shortness of breath was the most frequently reported symptom, correlating strongly with problems experienced with morning activities. Morning activities most affected by COPD were walking up and down stairs, putting on shoes and socks, making the bed, dressing, showering or bathing and drying. The majority of patients were not taking their medication in time for it to exert its optimal effect. Conclusions: Many patients consider the impact of COPD on morning activities to be substantial. Physicians should question patients about morning activities to assess disease impact and to advise regarding the optimal time to use therapy. This was an internet-based questionnaire survey and possible bias in patient selection and self-reported diagnosis of COPD and its severity should be taken into account.