33, range: 12-18) were compared to children with OCD and TS (OCD/

33, range: 12-18) were compared to children with OCD and TS (OCD/TS) (n = 12, mean age = 13.92, range:

9-17) and children with OCD-alone (OCD) (n = 12, mean age = 12.92, range: 9-17) on measures of obsessive-compulsive (OC) symptom frequency, severity, interference and other clinical variables.\n\nResults: Patients from the OCD/ASD group rated their OC symptoms as equally distressing, time consuming and contributing to a similar level of interference in functioning as patients in the OCD/TS and OCD groups. The types of symptoms were similar across groups but patients with OCD/TS check details reported greater frequency of ordering and arranging compulsions, and a trend towards more sexual obsessions. Patients with OCD/ASD reported more peer relationship problems compared with the other two groups.\n\nConclusions: Children with ASD may experience a similar level of impairment from OC symptoms as children with

TS plus OCD and children with OCD only. It is suggested that it is useful KPT-8602 to establish both diagnoses given that obsessions and compulsions may respond to treatment, and their alleviation may improve functioning in children on the autism spectrum.”
“Dictyonema huaorani, a new species represented by a well-developed specimen found in the Ecuadorian Amazon region, is described in this paper. The material was collected during a Harvard ethnobotanical expedition in 1981 and originally determined by Mason E. Hale Jr. as belonging in the genus Dictyonema (D. sericeum s. lat.) and possibly representing an undescribed species. The species is morphologically distinctive in forming densely woven, semicircular thalli, closely resembling those of the paleotropical D. ligulatum but lacking clamps and with hyphal sheath around the photobiont filaments that resembles those of Cyphellostereum species. The species was reported to have hallucinogenic properties and chemical analyses suggest certain substances present that are shared with the hallucinogenic mushroom Angiogenesis inhibitor Psilocybe cubensis. Due to our inability to use pure reference compounds and scarce

amount of sample for compound identification, however, our analyses were not able to determine conclusively the presence of hallucinogenic substances.”
“ArgBP2 is a multi-adapter protein involved in signal transduction associated to the cytoskeleton and was shown to regulate the migration and adhesion of pancreatic cancer cells thereby modulating their tumorigenicity. Here we describe the interaction of ArgBP2 with CIP4, a new associated protein identified by yeast two-hybrid. We found that both proteins modulated their reciprocal tyrosine phosphorylation catalyzed by the non-receptor tyrosine kinase c-Abl. We observed that, like ArgBP2, CIP4 directly interacted with WAVE1 and could enhance its phosphorylation by c-Abl. ArgBP2 and CIP4 acted synergistically to increase WAVE1 tyrosine phosphorylation.


“The reductive biotransformation of alpha-, beta-, gamma,


“The reductive biotransformation of alpha-, beta-, gamma, and delta-hexachlorocyclohexane isomers was investigated using five alternative electron donors (i.e., glucose plus rnethanol, glucose only, methanol only, acetate, and ethanol) in

a batch assay of an HCH-dechlorinating anaerobic culture. In addition, Selleckchem RSL-3 a life cycle assessment was conducted using the IMPACT2002+ method to evaluate the environmental effects of HCH bioremediation with the aforementioned electron donors. Results showed that the electron donors methanol plus glucose, ethanol, glucose, and methanol can significantly enhance the biotransformation of each HCH isomer. However, the amended electron donors and the byproduct of the MEK162 anoxic/anaerobic systems may negatively affect the environment (e.g., respiratory inorganic, land occupation, global warming, and non-renewable energy categories). These effects are attributed to the electron donor production processes. To avoid secondary pollutants, a linear relationship between the upper bound electron donor applications and HCH concentration was observed from an environmental perspective. Results indicated

that the methanol scenario was the most suitable option for the current research. (C) 2012, The Society for Biotechnology, Japan. All rights reserved.”
“Background/Aims: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare renal tubular disorder complicated by progressive renal failure during childhood or adolescence. Recently, causative mutations in the CLDN19 gene have been identified in FHHNC patients presenting with severe ocular involvement. The aim of the study was to investigate the molecular genetic defect VEGFR inhibitor underlying FHHNC in a consanguineous Pakistani family. Methods: Clinical and biochemical parameters of the proband were studied during the follow-up period over 5 years. Genotyping of 7 members of the family was performed by amplifying microsatellite markers, tightly linked to the CLDN16 and CLDN19 genes. The two genes were sequenced directly in an automated sequencer. PCR-RFLP assay and bioinformatic

analysis were performed to verify the identified mutation. Results: Genotyping revealed that the proband was homozygous for the marker loci tightly linked to the CLDN19 gene. Sequence analysis in the proband revealed homozygosity for a novel missense mutation in exon 3 of the CLDN19 gene (389G > A) resulting in G130D amino acid substitution. Bioinformatic analysis supported the pathogenicity of the identified mutation. Family screening revealed nephrolithiasis in 3 of 6 (50%) heterozygous carriers of the pathogenic mutation. Conclusion: This study supports the fundamental role of claudin 19 for magnesium homeostasis, normal tubular structures in the kidney, and undisturbed organization and development of the retina. Copyright (C) 2011 S.

9 +/- 7 2 years, mean diabetes duration 6 4 +/- 5 8 years Mean t

9 +/- 7.2 years, mean diabetes duration 6.4 +/- 5.8 years. Mean time of CSII use was 4.1 +/- 2.1 years. DAPT datasheet Good glycaemic control was defined by glycated haemoglobin (HbA(1c)) stratified by age (American Diabetes Association target levels). Improvement in glycaemic control was defined as a reduction of >= 0.5% in HbA(1c) from baseline. The change in the rate of severe hypoglycaemic or diabetic ketoacidosis events was also determined.\n\nResults\n\nThere was a significant sustained decrease in HbA(1c) with CSII for an average of 6 years, without increased rates of hypoglycaemia. Achievement of target HbA(1c) was significantly associated with the following parameters at pump initiation: lower HbA(1c)

(P < 0.001), younger age (< 12 years), shorter diabetes duration (P < 0.001) and more frequent daily self blood glucose monitoring (SBGM) (P < 0.01). Improved glycaemic control was associated with longer CSII use (P = 0.032) and higher HbA(1c) at CSII initiation (P < 0.001).\n\nConclusions\n\nSwitching patients to CSII resulted in sustained decrease in HbA(1c) and improved glycaemic control in patients with high HbA(1c). Young age, frequent SBGM and lower HbA(1c) at pump initiation were identified as predictors of achieving glycaemic targets with CSII.”
“During the last two decades, the outcome of various gene therapy selleck chemicals protocols lead to medical community disbelief.

Nevertheless, successful results obtained in recent years, repositioned gene therapy as a promising option for treatment of several diseases. Facing this renaissance of the international scientific community interest on gene therapy, it seems to be necessary for the generalist physician to understand its strength and limitations. The objective of this article is to comment the way gene therapy addresses nowadays the treatment of such different pathologies as neoplasias, infections and monogenic diseases.”
“The PE/PPE family of proteins, which constitute 10% of the coding capacity

of the mycobacterial genome, comprises a unique set of genes which have no known homologs and have expanded throughout their evolution. Their association with virulence has been implicated by several researchers in tuberculosis, but the molecular basis of their virulence is yet to be completely explored. PE/PPEgenes are mostly associated with the pathogenic IWR-1-endo in vivo strains of mycobacteria as many of them are known to be deleted in non-pathogenic ones. The non-essentiality of these genes for their in vitro growth but essentiality during infection highlights their active role in the host-pathogen interaction and consequently virulence. Even within the different strains of pathogenic mycobacteria and clinical isolates, many of the PE/PPE genes show sequence variation, pointing to their importance in providing antigenic variations, and have also been speculated to perform varied roles by differential expression during host-pathogen interaction.

It was found that the uniformed iPP nanofibers with averaged diam

It was found that the uniformed iPP nanofibers with averaged diameters less than 500 nm were fabricated by the suitable processing parameters. Otherwise, the processing immiscibility and rheological behavior of iPP/PLA blends were studied by means of dynamic mechanical analysis and capillary rheometer. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 2859-2866, 2012″
“Burning mouth syndrome (BMS) is a multifactorial condition which is still poorly understood. The aim of this study was to evaluate a group PXD101 ic50 of patients with BMS, as compared to a control group, and to describe related local and systemic factors. Records of patients referred to the Oral Pathology Service at the

School of Dentistry over a period of 7 years selleck compound were considered for the study, within which 32 patients with a diagnosis of BMS were found. A randomized group matched for age and gender was also evaluated for the study. Data were analyzed statistically using the SPSS 12.0 for Windows. Prevalence of BMS was 0.99% (32 BMS patients/3,243 records), considering that females were more commonly affected than were males and that the majority of the individuals were in their sixties. The univariate analysis performed comparing the two groups revealed statistical differences concerning the presence of gastrointestinal diseases

(p = 0.003) and urogenital diseases (p = 0.012). The intake of hypoxia-inducible factor pathway H-2 receptor antagonist and proton pump inhibitor drugs (p = 0.015) also proved to be significant. Logistic regression analysis confirmed that gastrointestinal and urogenital problems were indeed risk

factors that were solely associated with BMS. Although a diversity of related factors could be identified, gastrointestinal problems were the most prevalent, suggesting that the management of BMS patients requires attention and an appropriate approach to such disorders.”
“BACKGROUND Fag t 3 is a major allergenic protein in tartary buckwheat. The Maillard reaction commonly occurs in food processing, but few studies have been conducted on the influence of thermal processing on the allergenic potential of buckwheat allergen. The aim of the present study was to investigate the effects of autologous plant polysaccharides on the immunoreactivity of buckwheat Fag t 3 (11S globulin) following the Maillard reaction. RESULTS Fag t 3 and crude polysaccharides were prepared from tartary buckwheat (Fagopyrum tataricum) flour. After heating, the polysaccharides were covalently linked to Fag t 3 via a Maillard reaction, and the IgE/IgG-binding properties of Fag t 3 decreased dramatically, with significant changes also being observed in the electrophoretic mobility, secondary structure and solubility of the glycated Fag t 3. The great influence of glycation on IgE/IgG binding to Fag t 3 was correlated with a significant change in the structure and epitopes of the allergenic protein.

In the present study we demonstrate that IL-12R beta 2(-/-) mice

In the present study we demonstrate that IL-12R beta 2(-/-) mice develop earlier onset and more severe disease in the streptozotocin-induced model of diabetes, indicating predisposition of IL-12R beta 2-deficient mice to autoimmune diseases. T cells from IL-12R beta 2(-/-) mice

exhibited significantly higher proliferative responses upon TCR stimulation. www.selleckchem.com/products/beta-nicotinamide-mononucleotide.html The numbers of naturally occurring CD25(+)CD4(+) regulatory T cells (Tregs) in the thymus and spleen of IL-12R beta 2(-/-) mice were comparable to those of WT mice. However, IL-12R beta 2(-/-) mice exhibited a significantly reduced capacity to develop Tregs upon stimulation with TGF-beta, as shown by significantly lower numbers of CD25(+)CD4(+) T cells that expressed Foxp3. Functionally, CD25(+)CD4(+) Tregs derived from IL-12R beta 2(-/-) mice were less efficient than those from WT mice in suppressing effector T cells. The role of IL-12R beta 2 in the induction of Tregs was confirmed using small interfering RNA. These findings suggest that signaling via IL-12R beta 2 regulates both the number and functional maturity of Treg cells, which indicates a novel mechanism underlying the regulation of autoimmune diseases by the IL-12 pathway.”
“Background: Delivery room resuscitation (DRR) is a common emergency in newborns, particularly in resource-poor settings where intrapartum monitoring is not readily available. It may give

rise to oxidative stress in neonates due to reoxygenation and reperfusion of previously hypoxic and ischemic tissues. Urinary malondialdehyde (MDA), GDC-0994 being non-invasive, may serve as a marker of oxidative stress in these infants. Objective: We assessed oxidative stress in term newborns requiring DRR by measuring MDA levels in urine and serum samples collected at 12-24 h of age. Methods: The study population consisted of 41 cases and 63 healthy age-matched control infants. The inclusion criterion was a need for positive pressure ventilation at birth for >1 min. MDA levels were measured colorimetrically by thiobarbituric acid reaction. Results: Urinary and serum MDA levels Staurosporine in vivo were found to

be significantly higher in cases than in controls. Of the neonates given DRR, urinary and serum MDA values were elevated in those infants who passed meconium in utero, developed hypoxic ischemic encephalopathy or expired than in those who did not have these complications, but the difference was not significant. We found a significant correlation between urinary and serum MDA levels in infants given DRR. Conclusion: Newborns requiring DRR are subjected to significant oxidative stress which can be easily assessed by measuring urinary MDA levels. Copyright (C) 2008 S. Karger AG, Basel.”
“Cancer cells generate reactive oxygen species (ROS) resulting from mitochondrial dysfunction, stimulation of oncogenes, abnormal metabolism, and aggravated inflammatory activities.

Pluripotent ES cells are distinguished from differentiated cells

Pluripotent ES cells are distinguished from differentiated cells by a specialized chromatin state that is required to epigenetically regulate the ES cell phenotype. Recent studies show that in addition to pluripotency specific factors, chromatin remodeling enzymes play an important role in regulating ES cell chromatin and the capacity to self-renew Ulixertinib cost and to differentiate. Here we review recent studies that delineate the role of ATP dependent chromatin remodeling enzymes in regulating ES cell chromatin structure.”
“SNARE proteins and fusogenic viral membrane proteins represent the major classes of integral membrane

proteins that mediate fusion of eukaryotic lipid bilayers. Although both classes have different primary structures, they share a number of basic architectural features. There is ample evidence that the fusogenic function of representative fusion proteins is influenced by the primary structure of the single transmembrane domain (TMD) and the region linking it to the soluble assembly domains. Here, we used comprehensive non-redundant

datasets to examine potential over-and underrepresentation of amino acid types in the TMDs and flanking regions relative to control proteins that share similar Cyclopamine manufacturer biosynthetic origins. Our results reveal conserved overall and/or site-specific enrichment of beta-branched residues and Gly within the TMDs, ZD1839 underrepresentation of Gly and Pro in regions flanking the TMD N-terminus, and overrepresentation of the same residue types in C-terminal flanks of SNAREs and viral fusion proteins. Furthermore, the basic Lys and Arg are enriched within SNARE N-terminal flanking regions. These results suggest evolutionary conservation of key structural features of fusion proteins and are discussed in light of experimental findings that link these features to the fusogenic function of these proteins.”
“Reading disability (RD) and language impairment (LI) are common learning disabilities that

make acquisition and utilization of reading and verbal language skills, respectively, difficult for affected individuals. Both disorders have a substantial genetic component with complex inheritance. Despite decades of study, reading and language, like many other complex traits, consistently evade identification of causative and functional variants. We previously identified a putative functional risk variant, named BV677278 for its GenBank accession number, for RD in DCDC2. This variant consists of an intronic microdeletion and a highly polymorphic short tandem repeat (STR) within its breakpoints. We have also shown this STR to bind to an unknown nuclear protein with high specificity.

In this synthetic Overview, we present newly gathered data that s

In this synthetic Overview, we present newly gathered data that summarize how global patterns in coffee distribution and shade vegetation have changed and discuss implications for biodiversity, ecosystem services, and livelihoods. PR-171 cost Although overall cultivated coffee area has decreased by 8% since 1990, coffee production and agricultural intensification have increased in many places and shifted globally, with production expanding in Asia while contracting in Africa. Ecosystem services such as pollination, pest control, climate regulation, and nutrient sequestration are generally greater in shaded coffee

farms, but many coffee-growing regions are removing shade trees from their management. Although it is clear that there are ecological and socioeconomic benefits associated with shaded coffee, we expose the many challenges and future research priorities GNS-1480 cell line needed to link sustainable coffee management with sustainable livelihoods.”
“We describe here the synthesis of the allyl Le(3) trisaccharide antigen as well as that of an analogue of the Le(x) trisaccharide antigen, in which the galactose residue has been replaced by a glucose unit. Although successful fucosylations at O-4 of N-acetylglucosamine acceptors have been reported using perbenzylated thioethyl fucosyl donors under MeOTf activation, such conditions led in our case to the conversion of our acceptor to the corresponding alkyl imidates.

Indeed, in this synthesis of the Le(3) analogue, we demonstrate that the temporary protection of the N-acetyl group as a methyl imidate is advantageous to fucosylate at O-4. In contrast, we report here that glucosylation at O-4 of an N-acetylglucosamine monosaccharide Cl-amidine in vitro acceptor using the alpha-trichloroacetimidate of peracetylated glucopyranose as a donor proceeded in better yields under activation with excess BF(3)center dot

OEt(2) than that of the corresponding methyl imidate. Therefore, we conclude that activation of thioglycoside donors by MeOTf to glycosylate at O-4 of a glucosamine acceptor is best accomplished following the temporary protection of the N-acetyl group as a methyl imidate, especially when the donors are highly reactive and prone to degradation. In contrast, if donor and acceptor can withstand multiple equivalents of BF(3)center dot OEt(2), glycosylations at O-4 of a glucosamine acceptor with a trichloroacetimidate donor does not benefit from the temporary protection of the N-acetyl group as a methyl imidate. (C) 2008 Elsevier Ltd. All rights reserved.”
“Background: Phosphate binders’ constituents have alkalotic or acidotic properties and may contribute to acid base balance in haemodialysis patients. This study aimed to investigate the differential effects of phosphate binders on pre-dialysis serum bicarbonate in End Stage Kidney Disease patients on maintenance haemodialysis.

Devices currently available for local PWV measurement are mainly

Devices currently available for local PWV measurement are mainly based on ultrasound systems and have not yet been generalized to clinical practice since they require high

technical expertise and most of them are limited in precision, due to the lack of reliable signal processing methods. The present work describes a new type of probe, based on a double-headed piezoelectric (PZ) sensor. The principle of PWV measurement involves determination of the pulse transit time between the signals acquired simultaneously by both PZs, placed LY3039478 order 23 mm apart. The double probe (DP) characterization is accomplished in three main studies, carried out in a dedicated test bench system, capable of reproducing a range of clinically relevant properties of the cardiovascular system. The first study refers to determination of the impulse response (IR) for each PZ sensor, whereas the second one explores the existence of crosstalk between both transducers. In the last one, DP time resolution is inferred from a set of three different algorithms based on (a) the maximum of cross-correlation function, (b) the maximum amplitude detection and (c) the zero-crossing point identification. These values were compared with those Fedratinib nmr obtained by the reference method, which consists of the SB203580 cell line simultaneous acquisition of pressure

waves by means of two

pressure sensors. The new probe demonstrates good performance on the test bench system and results show that the signals do not exhibit crosstalk. A good agreement was also verified between the PWV obtained from the DP signals (19.55 +/- 2.02 ms(-1)) and the PWV determined using the reference method (19.26 +/- 0.04 ms(-1)). Although additional studies are still required, this probe seems to be a valid alternative to local PWV stand-alone devices.”
“Inflammatory back pain (IBP) is a concept, which elements characterize the spinal involvement of patients with ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA). The identification of patients with IBP depends on the clinical setting and the diagnostic value of several IBP criteria. IBP differentiation from non-inflammatory, mechanical chronic back might be sometimes difficult, but the role of IBP diagnosis in the early stage of axSpA and AS leads to a better treatment.”
“The evolution of occipitocervical fixation and new rigid universal screw-rod construct technology has allowed secure anchorage at each level of the occipitocervical junction with the elimination of rigid external orthoses. Rigid occipitocervical instrumentation constructs have achieved higher fusion rates and less postoperative immobilization-associated complications.

Euthymic individuals with a parental history of depression demons

Euthymic individuals with a parental history of depression demonstrate increased activation of hippocampal-related neural networks during a memory task, particularly in brain regions involved in processing the salience of stimuli. Changes in the activity of the ACC replicate previous findings in FH+ participants using different psychological tasks; this suggests that task-related abnormalities in the ACC may be a marker of vulnerability SNS-032 to depression. Increased levels of Glx in the hippocampus might also represent a risk biomarker but follow-up studies will be

required to test these various possibilities.”
“Radiation has large influence on the cytotoxicity, apoptosis and cell cycle arrest. The bioactivity of ruthenium(II) complex [Ru(dmb)(2)(DBHIP)](ClO4)(2) (Ru1) (DBHIP = 2-(3,5-dibromo-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) was investigated in the absence and presence of radiation. The cytotoxicity of Ru1 against MG-63 cells was evaluated by CCK-8 method. Ru1 shows high cytotoxicity upon radiation. Radiation can enhance the cytotoxicity of Ru1 on MG-63 cells. The apoptosis was studied by Hoechst 33258 staining method and flow cytometry. The reactive oxygen species, mitochondrial membrane potential, cell cycle arrest and western blot analysis were investigated in detail. The complex induces the apoptosis

buy BMS-345541 in MG-63 cells through ROS-mediated mitochondrial dysfunction pathway. (C) 2014 Elsevier B.V. All rights reserved.”
“The patient’s own evaluation of treatment can simplify communication between the patient and the treating physician; it provides additional important information for therapy control and improves patient compliance. Patient-reported outcomes (PROs) have already been examined in clinical studies among patients suffering from advanced ovarian cancer for a long time now and have made an important contribution with respect to the definition of a recognized standard of treatment for first-line therapy. This article describes the significance of PROs from the point of view of a social scientist,

a gynaecologist, and an affected patient.”
“Primary objective: This study examined the effectiveness selleck compound of a group approach to the treatment of anger management difficulties for people with severe traumatic brain injury (TBI).\n\nResearch design: Repeated-measures design with convenience sampling.\n\nMethod and procedure: Participants were community living clients of a tertiary brain injury service. The group programme consisted of 12 weekly sessions based on a cognitive behavioural therapy (CBT) model, with modifications to incorporate compensations for TBI-related cognitive impairment. Treatment effectiveness was measured using the State-Trait Anger Expression Inventory (STAXI), at pre-treatment, post-treatment and follow-up.\n\nMain outcomes and results: The programme was completed by 52 people across nine groups over the years 1998-2006 and 31 of these attended a follow-up session.

(C) 2012 Elsevier Ltd All rights reserved “
“Many studies o

(C) 2012 Elsevier Ltd. All rights reserved.”
“Many studies on methane (CH4) and nitrous oxide (N2O) emissions from livestock industries have revealed that livestock production directly contributes to greenhouse gas (GHG) emissions through enteric fermentation and manure management, which causes negative impacts on animal environment sustainability. In the present study, three essential values for GHG emission were measured; i.e., i) maximum CH4 producing capacity at mesophilic temperature (37 degrees C) from anaerobically stored manure in livestock category (B-0,B-KM, Korean livestock manure for B-0), ii) EF3(s)

value representing an emission factor for direct N2O emissions from manure management system S in the country, kg N2O-N kg N-1, at mesophilic (37 C) and thermophilic (55 degrees C) temperatures, selleck and iii) N-ex(T) emissions showing annual N excretion for livestock category T, kg N animal(-1) yr 1, from different livestock manure. Static incubation with and without aeration was performed to obtain the N2O and CH4 emissions from each sample, respectively. Chemical compositions of pre- and post- incubated manure were analyzed. Contents of total solids (% TS) and volatile solid (% VS), and the ratio of carbon to nitrogen (C/N) decrease significantly in all Smoothened Agonist solubility dmso the samples by C-containing biogas generation,

whereas moisture content (%) and pH increased after incubation. A big difference of total nitrogen content was not observed in pre- and post-incubation during CH4 and N2O emissions. CH4 emissions (g CH4 kg VS-1) from all the three manures (sows, layers and Korean cattle) were different and BVD-523 MAPK inhibitor high C/N ratio resulted in high CH4 emission. Similarly, N2O emission was found to be affected by % VS, pH, and temperature. The Box values for sows, layers, and Korean cattle obtained at 37 degrees C are 0.0579, 0.0006, and 0.0828 m(3) CH4 kg VS-1, respectively, whicli are much less than the default values in IPCC guideline (GL) except the

value from Korean cattle. For sows and Korean cattle, N-ex(T) values of 7.67 and 28.19 kg N yr(-1), respectively, are 2.5 fold less than those values in IPCC GL as well. However, N-ex(T) value of layers 0.63 kg N yr(-1) is very similar to the default value of 0.6 kg N yr(-1) in IPCC GLs for National greenhouse gas inventories for countries such as South Korea/Asia. The EF3(S) value obtained at 37 degrees C and 55 degrees C were found to be far less than the default value.”
“2-Aminopurine (2AP) is a fluorescent isomer of adenine and has a fluorescence lifetime of similar to 11 ns in water. It is widely used in biochemical settings as a site-specific fluorescent probe of DNA and RNA structure and base-flipping and -folding.