Fresh beetroots (Beta vulgaris subsp vulgaris var vulgaris), al

Fresh beetroots (Beta vulgaris subsp. vulgaris var. vulgaris), also known as red beet, were obtained from a local market in Santo André, SP, Brazil (sample A), commercial lyophilised beetroot (food-grade, sample B), and commercial betanin in dextrin (sample C) were purchased in Jena, Germany. Sample A: beetroots (0.5 kg) were peeled, sliced and homogenised in a centrifugal juice extractor (Phillips–Walita, ABT 263 RI1858) at maximum speed. The homogenate was centrifuged (3500 rpm, 30 min, 25 °C) and filtered (Whatman qualitative filter paper, grade 4). The supernatant

was stored at −20 °C and used within 5 days. Samples B and C: lyophilised beetroot and betanin in dextrin were resuspended in water (40–200 mg/mL) and filtered through a PTFE filter membrane (25 mm, pore size 0.45 μm) before purification. Samples A, B and C were submitted to purification by the following methods: gel permeation chromatography (GPC), normal phase column chromatography (NPC), reversed-phase column chromatography (RPC), reversed-phase high-performance liquid chromatography (RP-HPLC), ion-exchange chromatography learn more (IEX) and aqueous

two-phase extraction (ATPE). All experiments were performed in independent triplicates and purification yields are reported as mean ± standard deviation (mg/100 g of fresh (A) or dry (B and C) weight, namely raw weight) across all replicates. After purification, magenta fractions containing betanin were collected, pooled and the solution was concentrated (final volume of 1 mL) under reduced pressure (18 mbar, 25 °C). Afterwards, samples were submitted to UV–Vis spectroscopy and analytical HPLC analysis. Sephadex G-25 (6 g) and Sephadex LH-20 (5 g) were used as the stationary phases in a glass column and packed under deionised water. The elution was performed with deionised water as the mobile phase, flow rates of 2.2 mL/min (GPC-G25) and 0.25 mL/min (GPC-LH20). After Hydroxychloroquine mouse complete elution, the column was regenerated by washing with 5 column volumes of deionised water. Cleaning

and re-equilibration steps were performed between each elution. Silica gel 60 (15 g) was used as the stationary phase in a glass column and packed with the binary solvent mixture of methanol/water 8:2 v/v with 1% v/v glacial acetic acid. The elution was performed with the same binary solvent mixture at a flow rate of 0.7 mL/min. The silica gel 60 column was not regenerated. Silica gel 90 C18 (20 g) was used as stationary phase in a glass column and conditioned with methanol followed by deionised water. The elution was performed with deionised water at a flow rate of 0.3 mL/min. After complete elution, the column was regenerated by washing with 6 column volumes of methanol and re-equilibrated with water. Cleaning (MeOH) and re-equilibration (water) steps were performed between each elution.

The present findings

suggest that the consumption of WP a

The present findings

suggest that the consumption of WP and WPH promoted the accumulation of cardiac glycogen in the sedentary groups, similar to the results reported by Faria, Nery-Diez, Lollo, Amaya-Farfan, and Ferreira (2012), whereas no effect was found in the exercised groups. In conclusion, the data obtained in this study showed that the consumption of whey protein hydrolysate resulted in a greater increase in the concentration of HSP70, than that produced by the non-hydrolysed whey protein or by casein. This finding was observed in the gastrocnemius and soleus muscles and lung, but not in the spleen, kidney or heart. The data also suggested that the enzyme glutamine synthetase could be modulated by the different sources of protein in the diet. These results suggest that the increase in HSP70 selleck compound caused by the consumption of whey protein hydrolysate may affect different tissues in response mTOR inhibitor to physical exertion. The

authors are grateful to the Foundation for Research of the State of São Paulo, Brazil (FAPESP no. 2010/02419-0 and 2011/13035-1) for financial support and to Hilmar Ingredients (Hilmar, California, USA) for providing the whey protein products. “
“The açaí (Euterpe oleracea Mart.) and palmitero-juçara (Euterpe edulis Mart) palms are species native to Amazonia and the Atlantic Forest, respectively. The fruits are of economic importance in the Brazilian state of Pará. The fruits are considered a rich source of energy, and have been recognised for certain functional properties. In addition, the fruits are reported to be a substantial anthocyanin source, with high antioxidant activity ( Lichtenthäler et al., 2005, Rosso and Mercadante, 2007 and Rufino et al., 2010). Several analytical methods have been reported to detect anthocyanins in fruits, including UV–Vis spectroscopy (Lee & Francis, 1972), nuclear magnetic resonance (NMR) (Missang, Guyot, & Renard, 2003), mass spectrometry (MS) (Williams et al., 2002),

and capillary electrophoresis (CE) (Bednár et al., 2005). However, despite the reliability of these methods for anthocyanin detection, the approaches are destructive to the fruits, expensive, and generate chemical Calpain waste. In addition, some of the techniques, such as NMR, require specialised reagents and personnel, which limit their application beyond the laboratory. Due to the undesirable aspects of these analytical approaches, near infrared (NIR) spectroscopy has increased in acceptance in various analytical fields during the last decade (Geladi et al., 1999, Inácio et al., 2011, Neves et al., 2012 and Sakudo et al., 2009). NIR spectroscopy has the primary potential advantage of using intact samples presented directly to the instrument without sample preparation.

25 μm (diamond paste) and ultrasonically cleaned between each gri

25 μm (diamond paste) and ultrasonically cleaned between each grinding/polishing step for 3 min in acetone. The coupons were then ultrasonically cleaned in acetone and isopropyl alcohol for 7 min, dried with cold nitrogen gas, and positioned in a desiccator (room temperature) for 24 ± 1 h prior to exposure. The cleaning and aging procedure was selected to enable comparison with literature AZD2014 clinical trial data [4], and to allow the growth of a defined surface oxide. Contact angle measurements were made on 2–4 coupons, and X-ray

photoelectron spectroscopy performed on 2 coupons directly after polishing and after aging. The other coupons were put in acid cleaned polypropylene centrifuge tubes to which 4 mL of the respective solution was added (surface area to solution volume ratio of 0.5 cm−1). Four individual coupons were exposed

for each test condition, with one blank solution sample (no coupon added) exposed in parallel. Immersion was conducted at 37 ± 0.5 °C (Stuart platform-rocker incubator, 25 cycles/min of bilinear shaking) in: • 10 mM NaCl (0.584 g/L, Merck, initial pH 5.8), for 10 min (pH decreased to 5.1 ± 0.1) and 24 h (pH increased to 6.0 ± 0.1) In addition, four coupons were exposed at 60 ± 2 °C to 6 M HNO3 (initial pH <0) for 1 h (pH <0), and to 2 M NaOH (initial pH of 13.0) for 2 h (pH unchanged: 13.0). Another four coupons were exposed to 6 M HNO3 (as above), followed by measurement of contact angle. They were then cleaned according to the above procedure (acetone and isopropyl alcohol) and exposed to citric acid for 24 h (final pH 2.3 ± 0.03). After exposure, all coupons were rinsed with ultrapure water (18.2 MΩ cm) for 5 s (if not denoted differently). Subsequently AZD2281 molecular weight (<10 min), they were dried with cold nitrogen gas followed by immediate (<2 h) measurement of contact angle. To ensure accurate trace metal analysis of released iron from the stainless steel in solution all vessels and equipment were acid-cleaned in

10% HNO3 for at least 24 h, rinsed four times in ultrapure water (18.2 MΩ cm), and dried in ambient laboratory air. All chemicals were of analytical grade (p.a.) or puriss p.a. grade (in the case of nitric acid used for solution sample acidification prior to atomic absorption spectroscopy analyses). Static contact angles were determined using a PG-X pocket goniometer (Fibro Systems AB, Sweden). isothipendyl To avoid cross-contamination between the investigated fluids, each fluid had a unique set of tubes and syringes. The contact angle was measured after a 3–20 s delay, and after another 5–15 s delay between each drop. Individual static contact angle measurements were performed twice for each coupon and fluid. Between two and five coupons were measured for each exposure condition. Contact angle data is presented as average values and standard deviation between all coupons for each exposure condition (between 4 and 10 single measurements), or for single coupons (2 single measurements), as indicated in figures and tables.

4:1), Zn (1 3:1), and Cu (1 3:1) Among the examined elements, on

4:1), Zn (1.3:1), and Cu (1.3:1). Among the examined elements, only the level of MeHg in cord tissue was significantly (P < 0.001) higher (1.6 times) than that in placenta. However, Anti-diabetic Compound Library manufacturer the level of I-Hg level in placenta was significantly (P < 0.001) higher (2.4 times) than that in cord tissue. Consequently, the percentage of I-Hg vs. T-Hg in placenta (14.3%) was significantly (P < 0.001) and 3.3 times higher than

that in cord tissue (4.3%). The correlations between the placenta and cord tissue concentrations of MeHg, I-Hg, Pb, and Cd are depicted in Fig. 1. In all cases, the MeHg concentrations in cord tissue were higher than those in placenta, while the I-Hg and Cd concentrations in placenta were higher than those in cord tissues. In many cases, the Pb concentrations in placenta were higher than those of cord tissues. The correlations between the placenta and cord tissue concentrations of Se, Zn, and Cu are depicted in Fig. 2. MK 2206 In all cases, the Se concentrations in placenta were higher than those in cord tissue. In many cases, the

Zn and Cu concentrations in placenta were higher than those in cord tissue. The medians and interquartile ranges of the T-Hg, Pb, Cd, Se, Zn, and Cu concentrations in maternal and cord RBCs are shown in Table 2. Among the toxic elements, only the T-Hg level in cord RBCs was significantly (P < 0.001) higher (1.5 times) than that in maternal RBCs. The Pb and Cd levels in cord RBCs were significantly (P < 0.001) lower than those in maternal RBCs. The Se, Zn, and Cu levels in cord RBCs were significantly (P < 0.001 for Se and Zn; P < 0.01 for Cu) higher than those in maternal RBCs. Table 3 shows the Spearman rank correlation coefficients of MeHg in placenta and cord tissue vs. T-Hg in maternal and cord RBCs. The MeHg in placenta showed significant (P < 0.001) correlations with T-Hg in maternal and cord RBCs (rs = 0.80 and 0.91, PJ34 HCl respectively). The MeHg in cord tissue also

showed significant (P < 0.001) correlations with T-Hg in maternal and cord RBCs (rs = 0.75 and 0.85, respectively). Table 4 shows the Spearman rank correlation coefficients of T-Hg, Pb, Cd, Se, Zn, and Cu among placenta, cord tissue, maternal RBCs, and cord RBCs. The T-Hg in placenta showed significant (P < 0.001) and strong correlations with T-Hg in maternal and cord RBCs (rs = 0.81 and 0.90, respectively). The T-Hg in cord tissue showed significant (P < 0.001) and strong correlations with T-Hg in maternal and cord RBCs (rs = 0.74 and 0.85, respectively). In addition, the T-Hg showed significant (P < 0.001) and strong correlations among all the tissues examined. The Se in placenta showed significant but moderate correlations with the Se in maternal RBCs (rs = 0.38; P < 0.01) and cord RBCs (rs = 0.57; P < 0.001). The Se in cord tissue showed significant (P < 0.01) but moderate correlation with the Se in maternal RBCs (rs = 0.36).

Forbs and graminoids increased more frequently in abundance than

Forbs and graminoids increased more frequently in abundance than did shrubs across cutting, prescribed fire, and combined cutting + fire treatments (Fig. 4a–c). Shrub abundance usually decreased after treatments, a trend particularly evident after combined cutting + fire, where seven of eight (13%) studies reported that shrubs declined. Fewer studies measured species richness than measured cover, and no conclusive trends in richness emerged, except that forb richness may increase more frequently after treatment than other plant groups.

Results were mixed after wildfires: half of studies reported decreases in shrub cover while half reported increases (Fig. 4d). Frequency and magnitude of increase in non-native plant abundance (which was exclusively FK228 in vivo reported as cover) was least after cutting, intermediate BLU9931 order after prescribed fire, and greatest after cutting + prescribed fire (Fig. 5). Non-native species richness increased after all treatments, and most vigorously when cutting and prescribed fire were both applied, in all studies measuring

non-native richness. Despite these increases, non-natives comprised only small portions of total plant cover and richness. For example, non-native cover six years after prescribed fire was 1% (compared to 49% native) in mixed conifer forest in Grand Canyon National Park of Arizona (Huisinga et al., 2005), also 1% (compared to 12% native) one year after cutting + prescribed fire in the Sierra Nevada Mountains of California (Collins et al., 2007), and 10% (compared to 58% native and 4% non-native cover in the control) three years after cutting + fire in the University of Montana Lubrecht Experimental Forest (Dodson and Fiedler, 2006). Thus, native species largely constituted the total plant abundance and richness measures and corresponding responses to treatments (Fig. 2). It is noteworthy that few non-native plant data are available for wildfire Selleck Rucaparib to compare

with cutting and prescribed fire. No studies compared response to treatment between moist and dry mixed conifer forest. Effect sizes for total plant abundance after cutting (r2 = 0.04, n = 18) and prescribed fire (r2 = 0.01, n = 13) were not closely related to average long-term precipitation in study areas, indicating little relationship between response to treatment and average precipitation in this data set. Similarly, there was little relationship between effect sizes for species richness and average long-term precipitation of study areas for cutting (r2 = 0.11, n = 10) or prescribed fire (r2 = 0.00, n = 12). Results were mixed for the few studies comparing cutting intensity (Fig. 6). For prescribed fire and wildfire, high-severity burning generally (4 of 5 studies) displayed greater increase in total plant abundance and richness than did low-severity burning.

1 Extrusion parameters were feed moisture content of 25% (dry ba

1. Extrusion parameters were feed moisture content of 25% (dry basis), screw speed of 200 rpm, feed rate of 100 g/min and die diameter of 3.0 mm. The temperature profile from feed section to die exit was set to 50°C/110°C/110°C. The extrudate was dried directly in an air oven at 60°C

for 8 hours, and ground in a laboratory grinder to pass through a 400-μm sieve, then stored in plastic bags for further analysis. Moisture content, crude fat, protein, and ash were analyzed by the standard methods described in the Official Methods of Analysis of the Association of Official Analytical this website Chemists (AOAC) [12]. Total sugar and reducing sugar contents were determined according to the phenol–H2SO4 and dinitrosalicylic www.selleckchem.com/products/Bosutinib.html acid (DNS) methods, respectively [13] and [14]. The expansion ratio was determined by dividing the diameter of the extrudate by the diameter of the die (3 mm). The specific length was

evaluated as the straight length divided by the weight of extrudates. A total of 10 readings were recorded for each sample. Bulk density was determined after the extrudates were cut into pieces of approximately 2 cm in length by using a seed displacement method [15]. The color of the extrudate was measured with a colorimeter (CR-300; Minolta, Osaka, Japan). Color parameters L, a, and b were recorded separately. Water solubility index (WSI) and water absorption index (WAI) were measured by the modified method of Anderson et al [16]. A 1.5 g sample was dissolved in 30 mL of distilled water and shaken in the thermostatic water bath at 30°C for 30 minutes, and then centrifuged at 1000 × g for 10 minutes. The supernatant was decanted into a preweighted evaporating dish. The weight of the sediment

selleck chemicals was taken as WAI and was expressed as the unit g/g. The WSI is the weight of dry solids in the supernatant, which is expressed as a percentage of the original weight of the sample. Measurements were performed in triplicate for each sample. The dispersibility of the ginseng sample powder was determined according to the method of Shin et al [17] with minor modification. One gram of the ginseng powder was mixed with 30 mL distilled water. It was then shaken 10 times by hand and was left standing. The dispersion state after 10 minutes was observed and evaluated. Mechanical properties were determined with a Sun Rheometer (Compac-100; Sun Scientific Co., Ltd., Tokyo, Japan) equipped with a 2-kg load cell. The cross-head speed was set at 60 mm/minute. Ten replicates of extrudate were randomly selected and a mean value was recorded. The microstructure of extruded sample was examined with a field emission scanning electron microscope (MIRA II LMH; Tescan USA Inc., Cranberry Township, PA, USA). The accelerating voltage of scanning electron microscope was 10.0 kV. Crude saponin contents were determined according to the water-saturated n-butanol extraction method of Park et al [18] with some modification.

, 2003 and Tanaka et al , 2004) Furthermore, VEGF may also cause

, 2003 and Tanaka et al., 2004). Furthermore, VEGF may also cause a marked increase in inflammation, followed by an increase in mononuclear cells, eosinophils, and neutrophils (Homer and Elias, 2005). To the best of our knowledge, no other study has analyzed an experimental mouse model of obesity and chronic allergic asthma evaluating not only http://www.selleckchem.com/products/abt-199.html airway inflammatory and remodeling processes, but also the interaction between them. Nevertheless, our study presents limitations. The impact of obesity in asthma is more pronounced in females than in males. In the present

study, male mice were used, limiting the elucidation of a gender effect. Secondly, we were unable to gather data on leptin and adiponectin levels due to technical problems in the A/J mice. The levels of both hormones are increased in obesity and may influence asthma development (Shore et al., 2005 and Medoff et al., 2009). Third, inflammatory and fibrogenic mediators were not measured, due to the difficulty in obtaining a consistent pattern in this strain of mouse, preventing a more detailed understanding of remodeling mechanisms.

Finally, the Buxco Pulmonary Mechanics Processing System is unable to analyse proximal and distal airways MAPK inhibitor separately. However, even though lung histology was analyzed mainly in distal airways, it was able to reveal an impact of obesity on airway hyperresponsiveness and dynamic compliance. In conclusion, in the present experimental model of chronic allergic asthma, obesity induced greater lung inflammation and remodeling, which were associated with increased airway responsiveness to methacholine. Our experimental study indicates that obesity influences asthma severity by contributing to both the inflammatory and remodeling

processes. The authors would like to express their gratitude to Mr. Andre Benedito da Silva for animal care, Mrs. Thaiana Borges and for her skilful technical assistance during the experiments, Mrs. Ana Lucia Neves SPTBN5 da Silva for her help with microscopy, and Mrs. Moira Elizabeth Schöttler and Claudia Buchweitz for their assistance in editing the manuscript. This study was supported by Centers of Excellence Program (PRONEXFAPERJ), Brazilian Council for Scientific and Technological Development (CNPq), Rio de Janeiro State Research Supporting Foundation (FAPERJ), Coordination for the Improvement of Higher Education Personnel (CAPES), and São Paulo State Research Supporting Foundation (FAPESP). “
“The first licensed human therapeutic protein using the recombinant DNA technology was insulin, produced in 1982 on a large scale in Escherichia coli. However, due to the impossibility to express complex proteins with post-translational modifications in bacteria, animal cells have become a more attractive alternative for industrial purposes ( Butler, 2005). Animal cell cultures were developed in the last decade of the 19th century with the first attempts to hold pieces of fabric in plasma or biological fluids for several days or weeks.

3, Table 1) Ventilation at both very high and low volumes can le

3, Table 1). Ventilation at both very high and low volumes can lead to VILI (Frank et al., 2002). When connective tissue and parenchymal cells are exposed to high mechanical load, an adaptation process to tensile stress can start. Once extracellular matrix provides pulmonary structural mechanical support, it can be altered in response to mechanical

stress (Parker et al., 1997). Collagen represents one of these structural proteins and the stimulus to its synthesis can be pinpointed by the expression of PCIII mRNA expression (Raghu et al., Idelalisib solubility dmso 1985). Thus, we used PCIII mRNA as a marker of tissue damage since type-III procollagen is one of the first molecules to be synthesized during the lung fibrotic process (Raghu et al., 1985). Indeed, PCIII mRNA was significantly higher in V10P2 group at the end of OLV (Fig. 4). The early response of PCIII mRNA is in line with previous two-lung ventilation studies (Garcia et al., 2004, Farias et al., 2005 and De Carvalho et al., 2007). According to De Carvalho et al. (2007), overdistension due to mechanical ventilation with high VT leads to an early response of the extracellular matrix, resulting

in a significantly increase of PCIII mRNA expression. Interestingly, the extra pressure added to the respiratory system by the 3 cm H2O difference in PEEP (from V5P2 to V5P5) increased lung volume by 0.62 ml at the beginning of OLV and by 0.35 ml Tyrosine Kinase Inhibitor Library at the end of OLV (calculated considering Csp at each instance, as depicted in Fig. 2, and EELV to calculate compliance, and, then delta volume), whereas the change in lung volume due

to the extra gas volume added to the system from V5P2 to V10P2 was about 1 ml (= 5 ml/kg BW × 200 g BW). To our knowledge, no study has examined procollagen type-III expression during OLV. Under HSP90 the translational point of view, it should be stressed that in the present study both hemithoraces were open to the atmosphere, since the animals were in the supine position, as sometimes used in median sternotomy (Asaph et al., 2000). In this context, our results suggest that the use of high or low tidal volume without PEEP should be avoided during OLV applied in the face of median sternotomy, and perhaps under other sorts of thoracotomy as well. The authors acknowledge limitations in the current study. First, we used only one ventilation mode (VCV). It would be interesting to compare the present results with those in PCV ventilation mode. Second, hemodynamic parameters were not controlled. PEEP may interfere with vascular pressure and cardiac output. Third, OLV lasted just 1 h and, thus, we cannot exclude the possibility that longer ventilation time with low tidal volume (5 ml/kg), independently of PEEP level, could increase PCIII mRNA expression. Fourth, PCIII mRNA represents an indicator of PCIII synthesis, which may not happen after all.

Expansion of export timbering, mining, petroleum exploitation, in

Expansion of export timbering, mining, petroleum exploitation, industrial farming and ranching has impacted large areas of the greater Amazon forests and/or watercourses since the mid 20th century (Hecht and Cockburn, 2011, Clement, 1999, Fearnside, 2005 and Schmink and Wood, 1992; author’s observations in Para State, Brazil 1983–2009). Logging has intensified in the whitewater floodplains, destroying wide stretches of forest (Padoch et al., 1999). Areas along transport routes have been extensively deforested and Indians have been pushed out. Forests and wetlands have been cut and bulldozed to graze cattle or grow cash crops, and overgrazing and mechanized

cultivation have compacted soils, exacerbated erosion, and filled waters with sediment. Water sources and soil have been extensively polluted in petroleum extraction areas of Ecuador, and government-sponsored

GDC-0199 order agricultural colonization has disrupted and displaced indigenous people and diminished the forests (Southgate et al., 2009). In the interior south and north of the lower Amazon, aggressive promotion of corporate cattle ranching and industrial soybean agriculture for export has destroyed much of the Brazil nut resource and ruined soil quality; the groves have been extensively bulldozed in the last 20 years, removing ancient trees that had yielded sustainably for centuries (Smith selleck inhibitor et al., 1992:384–402; author’s observations, 1981–2009). When the forest is removed for pasture or urbanization, rainfall drops and temperatures increase. Savanna-pasture vegetation (Fig. 16) is much less able to survive drought, due to its shallow roots. The soil exposed to the elements loses its fertile layer, requiring heavy chemical fertilization, whose runoff pollutes ground water. Without the forests to shade the ground and hold and release moisture for rain, droughts have intensified, threatening even the cattle ranching and large farms (unpublished mid to late 20th century rainfall records from Monte Alegre municipality, and

Taperinha Plantation, collected by Erica Hagman). High international demand for minerals has led to widespread mining the and extraction in the interior of Amazonia (Cleary, 1990). Entire river drainages in the Xingu have been ravaged and polluted by mechanized sediment processing with mercury for gold (Roosevelt et al., 2009). For iron, entire landscapes in Carajas have been scraped off in open pit mines, leaving vast, devastated, lunar-like landscapes, devastated groves, and displaced indigenous people. Archeological sites and ancient human landscapes are also being rapidly destroyed (Roosevelt, 2010b). The early shell-mounds were ravaged by Ludwig’s bulldozers to get lime for fertilizer and road construction.

Much of the mechanism of X chromosome inactivation has been

Much of the mechanism of X chromosome inactivation has been BMN 673 manufacturer extensively studied and well characterized, including understanding the role of the antisense inhibitor, Tsix, to the proteins recruited to maintain the chromosome-wide inactivation, and the DNA–RNA–protein interactions that maintain X inactivation [ 4, 5, 6, 7 and 8]. However, a recent breakthrough was made in understanding how Xist is able to spread along the length of the entire chromosome without silencing other chromosomes or active areas of the X chromosome. Engreitz et al. using

1054 tiled probes to the 17-kb Xist transcript, pulled down unique sequences of genomic DNA bound to Xist at five time points during differentiation as Xist becomes induced. After ruling out the role of sequence motifs with Xist-recruiting ability, they found that the initial DNA sites bound by Xist were spatially proximal (based on Hi-C data) to the Xist locus [ 9••]. These results support a model that Xist spreads along the length of the chromosome by binding to distal sites that are spatially organized close to the newly transcribed Xist RNA. selleck chemicals llc By being able to modify chromatin structure at these regions, Xist is able to spread to newly silenced regions of the genome. Furthermore, regions that escape XCI are able to loop out and remain active while still permitting spatial spread of Xist. Since much more of the genome escapes XCI in humans

compared to mouse, it will be interesting to determine if this mechanism is conserved in humans. Other work has identified a new long non-coding RNA, XACT, specifically in human pluripotent stem cells [ 10••]. While not expressed in mice, XACT coats the active X chromosome and, in the absence of XIST, coats both chromosomes. Perhaps this reflects a human-specific mechanism by which cells prevent silencing of both X

chromosome, instead of, as in mouse, using TSIX as an antisense repressor. It is known that the human TSIX RNA has significantly less complementarity to human XIST than mouse Tsix and Xist, and its ability to act as an effective suppressor in this way has been questioned [ 11 and 12]. RNA Synthesis inhibitor This paper begins to shed light on human specific aspects of XCI that may underlie the mechanistic differences between mouse and human. Finally, two other studies provide additional pieces of the mechanistic puzzle. First is evidence for the role of Jarid2 in recruiting PRC2 to Xist RNA in helping to mediate inactivation [ 13•]. The second is the surprising finding that the first intron of Xist seems dispensable for Xist expression and normal function during XCI in stem cells and during development, despite the fact that the region exhibits strong pluripotency factor binding [ 14•]. Taken together these mechanistic results illustrate that there is still much to learn about XCI in both humans and mice. The role of the X chromosome in cancer has been well documented but much data is only correlational [15, 16, 17 and 18].