693 research outputs found
Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression
Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements
Kelt-17B: A Hot-Jupiter Transiting an A-Star in a misaligned orbit detected with Doppler Tomography
We present the discovery of a hot Jupiter transiting the V = 9.23 mag main-sequence A-star KELT-17 (BD+14 1881). KELT-17b is a , hot-Jupiter in a 3.08-day period orbit misaligned at −115fdg9 ± 4fdg1 to the rotation axis of the star. The planet is confirmed via both the detection of the radial velocity orbit, and the Doppler tomographic detection of the shadow of the planet during two transits. The nature of the spin–orbit misaligned transit geometry allows us to place a constraint on the level of differential rotation in the host star; we find that KELT-17 is consistent with both rigid-body rotation and solar differential rotation rates ( at significance). KELT-17 is only the fourth A-star with a confirmed transiting planet, and with a mass of , an effective temperature of 7454 ± 49 K, and a projected rotational velocity of it is among the most massive, hottest, and most rapidly rotating of known planet hosts
The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections
Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013
The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate
cocaine-induced changes in the concentrations of different
redox forms of cysteine (Cys) and homocysteine (Hcy),
and products of anaerobic Cys metabolism, i.e., labile,
reduced sulfur (LS) in the rat plasma. The above-mentioned
parameters were determined after i.p. acute and
subchronic cocaine treatment as well as following i.v.
cocaine self-administration using the yoked procedure.
Additionally, Cys, Hcy, and LS levels were measured
during the 10-day extinction training in rats that underwent
i.v. cocaine administration. Acute i.p. cocaine treatment
increased the total and protein-bound Hcy contents,
decreased LS, and did not change the concentrations of Cys
fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered
the total and protein-bound Cys concentrations while
LS level was unchanged. Cocaine self-administration
enhanced the total and protein-bound Hcy levels, decreased
LS content, and did not affect the Cys fractions. On the
other hand, yoked cocaine infusions did not alter the concentration
of Hcy fractions while decreased the total and
protein-bound Cys and LS content. This extinction training
resulted in the lack of changes in the examined parameters
in rats with a history of cocaine self-administration while in
the yoked cocaine group an increase in the plasma free Cys
fraction and LS was seen. Our results demonstrate for the
first time that cocaine does evoke significant changes in
homeostasis of thiol amino acids Cys and Hcy, and in some
products of anaerobic Cys metabolism, which are dependent
on the way of cocaine administration
A Cautionary Tale: MARVELS Brown Dwarf Candidate Reveals Itself To Be A Very Long Period, Highly Eccentric Spectroscopic Stellar Binary
We report the discovery of a highly eccentric, double-lined spectroscopic
binary star system (TYC 3010-1494-1), comprising two solar-type stars that we
had initially identified as a single star with a brown dwarf companion. At the
moderate resolving power of the MARVELS spectrograph and the spectrographs used
for subsequent radial-velocity (RV) measurements (R ~ <30,000), this particular
stellar binary mimics a single-lined binary with an RV signal that would be
induced by a brown dwarf companion (Msin(i)~50 M_Jup) to a solar-type primary.
At least three properties of this system allow it to masquerade as a single
star with a very low-mass companion: its large eccentricity (e~0.8), its
relatively long period (P~238 days), and the approximately perpendicular
orientation of the semi-major axis with respect to the line of sight (omega~189
degrees). As a result of these properties, for ~95% of the orbit the two sets
of stellar spectral lines are completely blended, and the RV measurements based
on centroiding on the apparently single-lined spectrum is very well fit by an
orbit solution indicative of a brown dwarf companion on a more circular orbit
(e~0.3). Only during the ~5% of the orbit near periastron passage does the
true, double-lined nature and large RV amplitude of ~15 km/s reveal itself. The
discovery of this binary system is an important lesson for RV surveys searching
for substellar companions; at a given resolution and observing cadence, a
survey will be susceptible to these kinds of astrophysical false positives for
a range of orbital parameters. Finally, for surveys like MARVELS that lack the
resolution for a useful line bisector analysis, it is imperative to monitor the
peak of the cross-correlation function for suspicious changes in width or
shape, so that such false positives can be flagged during the candidate vetting
process.Comment: 16 pages, 11 figures, 6 table
Exploiting inflammation for therapeutic gain in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC
The impact of attention to news about tax changes on the stock market
We approach to point out new direction of measurement the attention of the news related to changes in taxes by using the application Google Trends. The objective of the study is to extend literature that investigates the impact of the information's search intensity provided by Google Trends on capital market. We show that increasing attention on tax changes measured by Google search decrease stock prices of the US companies listed on NASDAQ. Moreover, we focus on abnormal Google searches related to particular shocks. The study investigates the positive relationship between attention to news about tax changes and stock prices in a specific year. The cross-sectional analysis employs data from 2004 and 2005. At that time, President George Bush enacted tax breaks for overseas corporate profits, which had a great impact on search intensity within the period. Additionally, we differentiate between market capitalisation by using the dummy variables to put on the role changes of probability on selected datasets. The results confirmed higher impact of attention on large cap companies and point out the importance of sentiment analysis at liquid markets.O
The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns
Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research
Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit
TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and
short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary
systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged
(~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of
0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the
SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements
from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of
~2 years. The best Keplerian orbital fit parameters were found to have a period
of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a
semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if
sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass
ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for
short period stellar companions to solar-like (Teff ~< 6000 K) stars. One
possible way to create such a system would be if a triple-component stellar
multiple broke up into a short period, low q binary during the cluster
dispersal phase of its lifetime. A candidate tertiary body has been identified
in the system via single-epoch, high contrast imagery. If this object is
confirmed to be co-moving, we estimate it would be a dM4 star. We present these
results in the context of our larger-scale effort to constrain the statistics
of low mass stellar and brown dwarf companions to FGK-type stars via the
MARVELS survey.Comment: 22 pages; accepted in A
The clinical features of the piriformis syndrome: a systematic review
Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis
Using endogenous saccades to characterize fatigue in multiple sclerosis
Purpose
Multiple Sclerosis (MS) is likely to cause dysfunction of neural circuits between brain regions increasing brain working load or a subjective overestimation of such working load leading to fatigue symptoms. The aim of this study was to investigate if saccades can reveal the effect of fatigue in patients with MS.
Methods
Patients diagnosed with MS (EDSS<=3) and age matched controls were recruited. Eye movements were monitored using an infrared eyetracker. Each participant performed 40 trials in an endogenous generated saccade paradigm (valid and invalid trials). The fatigue severity scale (FSS) was used to assess the severity of fatigue. FSS scores were used to define two subgroups, the MS fatigue group (score above normal range) and the MS non-fatigue. Differences between groups were tested using linear mixed models.
Results
Thirty-one MS patients and equal number of controls participated in this study. FSS scores were above the normal range in 11 patients. Differences in saccade latency were found according to group (p<0.001) and trial validity (p=0.023). Differences were 16.9 ms, between MS fatigue and MS non-fatigue, 15.5 ms between MS fatigue and control. The mean difference between valid and invalid trials was 7.5 ms. Differences in saccade peak velocity were found according to group (p<0.001), the difference between MS fatigue and control was 22.3°/s and between MS fatigue and non-fatigue was 12.3°/s. Group was a statistically significant predictor for amplitude (p<0.001). FSS scores were correlated with peak velocity (p=0.028) and amplitude (p=0.019).
Conclusion
Consistent with the initial hypothesis, our study revealed altered saccade latency, peak velocity and amplitude in patients with fatigue symptoms. Eye movement testing can complement the standard inventories when investigating fatigue because they do not share similar limitations. Our findings contribute to the understanding of functional changes induced by MS and might be useful for clinical trials and treatment decisions.We would like to acknowledge that part of this work has been presented at 3rd International Porto Congress of Multiple Sclerosis, February 27–28, 2015, Porto, Portugal and ECEM 2015 | XVIII. European Conference on Eye Movements, August 16–21, 2015, Viena, Austria. We thank the Multiple Sclerosis Association “Todos com a Esclerose Multiple (TEM)” and the Clinical and Academic Centre (CAA-Hospital de Braga) for their support financial support and for providing facilities for data collection, respectively. We also acknowledge: i) Carla Sofia for recruiting all the MS participants and most of the controls, ii) Two anonymous reviewers for their opinion about an early version of this manuscript and iii) Liz Pearce for proofreading the manuscript. Vision Rehabilitation Lab. receives founding from Shamir Portugal and from grant PTDC/DTP-EPI/0412/2012, Fundação para a Ciência e a Tecnologia, co-financiado pelo FEDER através do COMPETE.info:eu-repo/semantics/publishedVersio
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