Guanine-rich RNA sequences can fold into four-stranded structures, termed G-quadruplexes (G4-RNAs), whose biological roles are poorly understood, and in vivo existence is debated. To profile ...biologically relevant G4-RNA in the human transcriptome, we report here on G4RP-seq, which combines G4-RNA-specific precipitation (G4RP) with sequencing. This protocol comprises a chemical crosslinking step, followed by affinity capture with the G4-specific small-molecule ligand/probe BioTASQ, and target identification by sequencing, allowing for capturing global snapshots of transiently folded G4-RNAs. We detect widespread G4-RNA targets within the transcriptome, indicative of transient G4 formation in living human cells. Using G4RP-seq, we also demonstrate that G4-stabilizing ligands (BRACO-19 and RHPS4) can change the G4 transcriptomic landscape, most notably in long non-coding RNAs. G4RP-seq thus provides a method for studying the G4-RNA landscape, as well as ways of considering the mechanisms underlying G4-RNA formation, and the activity of G4-stabilizing ligands.
Malnutrition predicts poorer clinical outcomes for people with cancer. Older adults with cancer are a complex, growing population at high risk of weight-losing conditions. A number of malnutrition ...screening tools exist, however the best screening tool for this group is unknown. The aim was to systematically review the published evidence regarding markers and measures of nutritional status in older adults with cancer (age ≥ 70). A systematic search was performed in Ovid Medline, EMBASE, Web of Science, CINAHL, British Nursing Database and Cochrane CENTRAL; search terms related to malnutrition, cancer, older adults. Titles, abstracts and papers were screened and quality-appraised. Data evaluating ability of markers of nutritional status to predict patient outcomes were subjected to meta-analysis or narrative synthesis. Forty-two studies, describing 15 markers were included. Meta-analysis found decreased food intake was associated with mortality (OR 2.15 2.03-4.20 p = < 0.00001) in univariate analysis. Prognostic Nutritional Index (PNI) was associated with overall survival (HR 1.89 1.03-3.48 p = 0.04). PNI markers (albumin, total lymphocyte count) could be seen as markers of inflammation rather than nutrition. There a suggested relationship between very low body mass index (BMI) (<18 kg/m
) and clinical outcomes. No tool was identified as appropriate to screen for malnutrition, as distinct from inflammatory causes of weight-loss. Risk of cancer-cachexia and sarcopenia in older adults with cancer limits the tools analysed. Measures of food intake predicted mortality and should be included in clinical enquiry. A screening tool that distinguishes between malnutrition, cachexia and sarcopenia in older adults with cancer is needed.
Abstract
Current knowledge suggests that intimal smooth muscle cells (SMCs) in native atherosclerotic plaque derive mainly from the medial arterial layer. During this process, SMCs undergo complex ...structural and functional changes giving rise to a broad spectrum of phenotypes. Classically, intimal SMCs are described as dedifferentiated/synthetic SMCs, a phenotype characterized by reduced expression of contractile proteins. Intimal SMCs are considered to have a beneficial role by contributing to the fibrous cap and thereby stabilizing atherosclerotic plaque. However, intimal SMCs can lose their properties to such an extent that they become hard to identify, contribute significantly to the foam cell population, and acquire inflammatory-like cell features. This review highlights mechanisms of SMC plasticity in different stages of native atherosclerotic plaque formation, their potential for monoclonal or oligoclonal expansion, as well as recent findings demonstrating the underestimated deleterious role of SMCs in this disease.
Polysaccharides are natural macromolecular polymers that are widely distributed in various food resources and have attracted much attention due to their significant bioactivities. Sulfated ...polysaccharides refer to polysaccharides containing sulfate groups on sugar units. A large number of studies have characterized and evaluated the biological relevance of sulfated polysaccharides, which shows great potential in terms of immunological activity.
Through a critical analysis of current research literature regarding sulfated polysaccharides, this review will give an overview of the immunomodulatory properties and signaling mechanisms of natural or modified sulfated polysaccharides. The effects of the degree of substitution (DS), molecular weight, and structure on immunomodulatory effects will also be discussed.
The mechanisms by which sulfated polysaccharides exert their immunological activity is mainly due to the regulation of macrophage function, natural killer cells, and T/B lymphocytes, together with the stimulation of the immune responses of lymphocytes and the activation of the complement system. The immunological activity of sulfated polysaccharides depends not only on the source of the polysaccharide but also on structural characteristics, such as molecular weight and DS. Studies on the mechanisms of immune function have shown that the action of sulfated polysaccharides is a complex process that may be regulated by one or more pathways. Nevertheless, the link between the immunological mechanisms and structure of sulfated polysaccharides requires further exploration.
•Sulfated polysaccharides have shown great potential for immunological activity.•Sulfated polysaccharides can bind to multiple receptors to regulate immune function.•Sulfated polysaccharides regulate immune function through multiple pathways.•Structure of sulfated polysaccharides affects its regulation of immune function.
The On/Off Nature of Star-Planet Interactions Shkolnik, Evgenya; Bohlender, David A; Walker, Gordon A. H ...
Astrophysical journal/The Astrophysical journal,
03/2008, Volume:
676, Issue:
1
Journal Article
Peer reviewed
Open access
Evidence suggesting an observable magnetic interaction between a star and its hot Jupiter appears as a cyclic variation of stellar activity synchronized to the planet's orbit. In this study we ...monitored the chromospheric activity using several stellar activity indicators of seven stars with hot Jupiters using new high-resolution echelle spectra collected with ESPaDOnS over a few nights in 2005 and 2006 from the CFHT (Ca ii H lambda3968, K lambda3933, the Ca ii infrared triplet IRT lambda8662 line, H alpha lambda6563, and He i lambda5876). Synchronicity of the Ca ii H and K emission of HD 179949 with its planet's orbit is clearly seen in four out of six epochs, while rotational modulation with image is apparent in the other two seasons. We observe a similar phenomenon on upsilon And. This on/off nature of star-planet interaction (SPI) in the two systems is likely a function of the changing stellar magnetic field structure throughout its activity cycle. Variability in the transiting system HD 189733 is likely associated with an active region rotating with the star; however, the flaring in excess of the rotational modulation may be associated with its hot Jupiter. As for HD 179949, the peak variability as measured by the mean absolute deviation (MAD) for both HD 189733 and tau Boo leads the subplanetary longitude by image70 degree . The tentative correlation between this activity and the ratio of image to the planet's rotation period, a quantity proportional to the hot Jupiter's magnetic moment, first presented by Shkolnik and coworkers remains viable. This work furthers the characterization of SPI, improving its potential as a probe of extrasolar planetary magnetic fields.
Despite the increasing use of optogenetics in vivo, the effects of direct light exposure to brain tissue are understudied. Of particular concern is the potential for heat induced by prolonged optical ...stimulation. We demonstrate that high-intensity light, delivered through an optical fiber, is capable of elevating firing rate locally, even in the absence of opsin expression. Predicting the severity and spatial extent of any temperature increase during optogenetic stimulation is therefore of considerable importance. Here, we describe a realistic model that simulates light and heat propagation during optogenetic experiments. We validated the model by comparing predicted and measured temperature changes in vivo. We further demonstrate the utility of this model by comparing predictions for various wavelengths of light and fiber sizes, as well as testing methods for reducing heat effects on neural targets in vivo.
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•Fiber optic light delivery is sufficient to increase cortical firing rates in vivo•An optogenetics MATLAB package is provided for predicting light and heat spread•In vivo temperature recordings validate model predictions of heat induction
Stujenske et al. demonstrate that light emitted into the brain for optogenetics is sufficient to increase local temperature and the firing rates of single neurons. They provide a software package for modeling light and heat spread from optical fibers.
Theta oscillations synchronize the basolateral amygdala (BLA) with the hippocampus (HPC) and medial prefrontal cortex (mPFC) during fear expression. The role of gamma-frequency oscillations in the ...BLA is less well characterized. We examined gamma- and theta-frequency activity in recordings of neural activity from the BLA-HPC-mPFC circuit during fear conditioning, extinction, and exposure to an open field. In the BLA, slow (40–70 Hz) and fast (70–120 Hz) gamma oscillations were coupled to distinct phases of the theta cycle and reflected synchronous high-frequency unit activity. During periods of fear, BLA theta-fast gamma coupling was enhanced, while fast gamma power was suppressed. Periods of relative safety were associated with enhanced BLA fast gamma power, mPFC-to-BLA directionality, and strong coupling of BLA gamma to mPFC theta. These findings suggest that switches between states of fear and safety are mediated by changes in BLA gamma coupling to competitive theta frequency inputs.
•There are two bands of theta-nested gamma in the BLA during fear expression•BLA cells that phase-lock to fast gamma increase firing during safety•Fast gamma couples to BLA theta during fear and to mPFC theta during safety•mPFC-to-BLA fast gamma directionality indicates safety in three behavioral paradigms
The medial prefrontal cortex is thought to inhibit fear through interactions with the basolateral amygala (BLA). Stujenske et al. show that, during safety, gamma oscillations in the BLA are modulated by medial prefrontal cortex activity, perhaps mediating this inhibition.
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