This should not be uncritically accepted as a failure of Galunisertib chemical structure voluntary drive,

firstly because patients with COPD have been shown to be able fully to activate their diaphragm (Topeli et al., 2001) and secondly because we also found a strong correlation between intracortical facilitation and a non-volitional test of diaphragm strength, the TwPdi. Interestingly, although volitional measures of inspiratory muscle strength have tended to improve, at least in patients with restrictive pulmonary disease, following the initiation of NIV, TwPdi does not (Nickol et al., 2005). It is certainly the case that cortical areas, to which vagal afferents including peripheral chemoreceptors and pulmonary stretch receptors project, are involved in the response to respiratory loading and the sensation of breathlessness (Banzett et al., 2000 and Isaev et al., 2002). The neural pathways involved in the control of breathing have the capacity for considerable functional plasticity both in adapting throughout life and in response to stress (Mitchell and Johnson, 2003). In experimental models, hypercapnia is associated in the long term with a depression in phrenic output (Baker et al., 2001). Our finding of a correlation between intracortical inhibition and PaCO2 is consistent with this and may represent a novel mechanism involving

cortical as well as brainstem responses to explain the phenomenon. It is not clear whether the increased intracortical inhibition observed in COPD patients with increasing hypercapnia is specific for the respiratory muscles or a non-specific response. In favor GDC-0199 research buy of a specific process is our previous finding that the corticospinal pathways to the diaphragm and abdominal muscles were more excitable in patients with COPD whereas those to the quadriceps were not, implying that these changes were specific to muscles involved in breathing PLEKHB2 (Hopkinson et al., 2004). Moreover in another study in healthy subjects, hypercapnia

increased diaphragm MEP amplitude and decreased central conduction time but had no effect on the response of a small hand muscle (Straus et al., 2004). In favor of a more generalized process is the fact that a prolonged cortical silent period, a measure of inhibitory tone, has been demonstrated in non-respiratory muscles of a population of patients with obesity hypoventilation and obstructive sleep apnea who were hypercapnic and hypoxic (Civardi et al., 2004). In another study, patients with COPD had reduced intracortical inhibition for the first dorsal interosseous muscle during acute exacerbations which returned to normal when they had been established on long term oxygen therapy and were studied several months later (Oliviero et al., 2002). To our knowledge the effect of hypoxemia and hypercapnia on the diaphragm response to paired TMS has not previously been assessed.

Additionally, this variable showed ICC values that indicate good reliability between the measures. In a study by Georgiadou et al. (2007), four of 20 subjects with chronic obstructive pulmonary disease (COPD) were evaluated on two different days at rest and during an incremental exercise on a cycle ergometer using the OEP system. Only a linear regression analysis was used to analyze the reproducibility of the measurements between the two days and only the values of the correlation coefficients were reported for comparison of Veicw, Veecw and inspiratory reserve volume between the two occasions. They observed correlations of high

magnitude for changes for these variables in all stages of incremental exercise on a cycle ergometer in relation to rest. However, details about the experimental protocol were not provided. The inter-rater reliability ensures that there is no significant difference in measurements Selleckchem AZD0530 when performed by different examiners (Portney and Watkins, 2008). In this study, the

ICC values observed were higher than 0.75 for most variables and the coefficient of variation was less than EX 527 solubility dmso or equal to 10% for all variables at rest and during exercise. The lowest ICC values were found for the variables Vrcp%, Vrca%, Vrc%, and Vab% during exercise and can be explained by the small between-individual variability observed during ICC calculation. There was also significant reduction in the variance of these variables between rest and exercise, which may have directly influenced the ICC values. This response was not observed for intra-rater reliability, probably because of the larger number of subjects evaluated. Additionally, the coefficient of variation of the Method Error, which is minimally influenced by between-subject variability, was less than 10% for those variables. Neratinib chemical structure Significant differences between examiners were found for the variables

Vrcp% and Vrca% at rest and for the variable Vrca% during exercise, as well as for the variables Veecw and Veicw, both at rest and during exercise. These results suggest the influence that different examiners can have on variables that reflect the response of each rib cage compartment separately. Therefore, this aspect should be considered when designing a study with the OEP system. In a study by Aliverti et al. (2009), three of the twenty patients with COPD evaluated underwent the study protocol on three different occasions, with OEP markers positioned by two different examiners. It was observed that the positioning of the markers by different evaluators did not affect the classification of the asynchrony motion. However, the experimental protocol was poorly described and the comparisons between the different variables obtained by OEP were not performed. The main limitation of the study is the sample size of the inter-rater reliability protocol.

Antibodies against cytochrome c, poly (adenosine diphosphate-ribose) polymerase (PARP), Bak, Bax, α-tubulin were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibodies against caspase-8, -9, and cytochrome c oxidase II (Cox II) were purchased from Cell Signaling Technology (Beverly, MA, USA). Clarity Western ECL Substrate Kit was purchased from Bio-Rad (Hercules, CA, USA). HeLa, SW111C, and Doxorubicin datasheet SW480 cells were grown in DMEM supplemented with 10% (by volume) heat-inactivated newborn calf serum, 100 μg/mL of streptomycin 100 U/mL of penicillin, at 37°C in a humidified atmosphere with 5% CO2. The SG methanol extract was analyzed as a previous

report described [38]. Briefly, SG was dissolved in MeOH (3 mg/mL), and filtered with 0.45μm Millipore filter, and the solution was analyzed with a Waters 2695 liquid chromatograph (Waters Corporation, Milford, MA, USA) fitted with Knauer C-18, reverse-phase

column (Knauer, Berlin, Germany; 5μm,φ250 mm × 3 mm) utilizing the solvent gradient system. The mobile phase consisted of acetonitrile water (Solvent A) and water (Solvent B) and the flow rate was 0.6 mL/min. The detector was a Waters 2996 PDA Detector (Waters Corporation). The gradient elution was used as follows: 0–20 min, 20% A; 20–31 min, linear gradient from 20–32% A; 31–40 min, linear gradient from 32–43% A; 40–70 min, linear gradient from 43–100% A; and 70 min, 100% A. Exponentially growing cells were seeded into a 96-well plate at 0.8 × 104 cells/well in triplicate. MEK inhibitor cancer Methane monooxygenase After incubation for 20 h, cells were treated with increasing concentrations of SG, epirubicin, or paclitaxel for 48 h. At 44 h posttreatment, 20 μL of MTT (5 mg/mL) was added to each well and incubated for 4 h. Then 150 μL of DMSO was added to every well to solubilize the formazan crystals formed by viable cells, and the color intensity was measured at 550 nm with an enzyme-linked immunosorbent assay plate reader (TECAN, Männedorf, Switzerland). HeLa cells were cultured for 20 h and then treated with 80 μg/mL SG with 0.5 μg/mL epirubicin or 10nM paclitaxel alone or combined for 24 h. HeLa cells were harvested, washed with ice-cold phosphate buffered saline (PBS),

and stained with annexin V/PI reagent as described previously [3]. The percentage of annexin V (+) cells was determined by flow cytometry (Becton Dickinson FACS Calibur Cytometer, San Jose, CA, USA). The percentage of annexin V (+) cells indicates the frequency of total apoptotic cells. As described [39], HeLa were treated and harvested. 50 μg whole-cell lysates were incubated with 200nM Ac-LEHD-AFC (for caspase-9), Ac-IETD-AFC (for caspase-8), and Ac-DEVD-AFC (for caspase-3) in a reaction buffer containing 20mM 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) pH 7.4,10mM dithiothreitol (DTT), 10% sucrose, 100mM NaCl, and 0.1% 3-((3-Cholamidopropyl)dimethylammonium)-1-propanesulfonate (CHAPS) at 37°C for 1 h. The reaction was monitored by fluorescence excitation at 405 nm and emission at 505 nm.

Rg3 can induce apoptosis and cell cycle arrest in different cancer cells via different pathways such as downregulating hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) [18], [19], [20] and [21]. Rk1 was investigated to inhibit telomerase activity and cell growth and induce apoptosis through activation of caspase-8 and -3 via ERK pathway, whereas another article demonstrated that Rk1 could induce G1 arrest and autophagy [22] and [23]. Rg5 blocks the cell cycle at the Gl/S transition phase by increasing p21Cip/WAF1 and decreasing cyclin E and CDK2 [24]. Epirubicin is a third-generation anthracycline that treats a broad

spectrum of cancers, including cervical, breast, lung (especially small cell lung

cancer), ovarian, stomach, Selleckchem Cobimetinib colon, and bladder, and malignant lymphoma [25] and [26]. Similar to widely used find protocol anticancer drugs, epirubicin exhibits some adverse effects on blood, the stomach, and the heart; these effects largely depend on the applied doses [27]. Paclitaxel is another important anticancer drug that is widely used as a chemotherapeutic agent for treating ovarian, breast, lung, colorectal, bladder, prostate, and gastric cancer, melanoma, and lymphoma [28], [29] and [30]. Paclitaxel, which is an inhibitor of microtubule degradation, induces cell cycle arrest at the G2/M phase [31] and [32] and ultimately apoptosis [33] and [34]. This drug also has significant adverse effects, such as hypersensitivity, neutropenia syndrome, neurotoxicity, heart rhythm

disorders, and intracellular toxicity [35], [36] and [37]. Therefore, developing adjuvant agents to potentiate the anticancer activities of epirubicin and paclitaxel and to minimize their adverse effects is significant. In the current study, SG significantly Fluorometholone Acetate potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. SG was provided by Dr. Jeong Hill Park, College of Pharmacy, Seoul National University, Seoul, Korea. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and dimethylsulfoxide (DMSO) were purchased from Sigma–Aldrich (St. Louis, MO, USA). Epirubicin was acquired from Pfizer (Wuxi, China). Newborn calf serum and Dulbecco modified Eagle’s medium (DMEM) were purchased from Gibco (Life Technologies, Grand Island, NY, USA). Caspase substrates Ac-DEVD-AFC, Ac-IETD-AFC, and Ac-LEHD-AFC were purchased from Calbiochem (La Jolla, CA, USA). The Mitochondria Isolation Kit was purchased from Pierce (Rockford, IL, USA). Annexin V-FITC Apoptosis Detection Kit was purchased from KeyGEN Biotech (Nanjing, China).

An influential theory in this field is “scanpath theory” (Norton & Stark, 1971), which proposed that reinstatement of the sequence of eye-movements made during encoding of a visual stimulus plays a causal role in its subsequent successful recognition. A hard interpretation of this theory entails that recapitulation of eye-movements made during encoding of visual scenes facilitates successful recall. However, a recent study BGB324 research buy by Martarelli and Mast (2013) manipulated eye-position during pictorial recall and found that there was no increase in memory accuracy when participants looked at areas where stimuli had previously appeared, in comparison to when

they looked at non-corresponding areas of screen. Similarly, Foulsham and Kingstone (2013) have recently reported a series of experiments in which participants’ fixations were constrained during GDC 0199 encoding and recognition of images in order to manipulate scanpath similarity. Although scanpath similarity was a predictor of recognition accuracy, there was no recognition advantage when participants re-viewed their own fixations of a

scene versus someone else’s, or for retaining serial order of fixations between encoding and recognition. Foulsham and Kingston conclude that while congruency in eye-movements between encoding and retrieval is beneficial for scene recognition, there is no evidence to suggest recapitulation of the exact scanpath at encoding is necessary for accurate recall. Our own results are broadly in line with these recent findings, as there is no evidence from Experiment 3 in the present study that the ability to engage in saccade preparation to memorized locations

is necessary for their accurate recall. Thus, while the rehearsal of directly salient locations in the oculomotor system allows for optimal spatial memory at recall, we regard this as a contributing mnemonic mechanism that operates in conjunction with visually-based strategies such as mental path construction or visual imagery (Parmentier et al., 2005 and Rudkin et al., 2007). Critically, we have previously shown during that eye-abduction only reduces, rather than abolishes, spatial memory even when applied across all encoding, maintenance, and retrieval stages of a trial (Ball et al., 2013). Therefore, clearly the involvement of oculomotor encoding and rehearsal enhances spatial memory for a sequence of visually-salient locations rather than critically enables it. However, this position is not dissimilar to that observed when articulatory suppression is used to prevent subvocal rehearsal of words and digits during verbal working memory ( Baddeley et al., 1975 and Murray, 1967), where verbal memory span is significantly reduced but not abolished ( Baddeley, 2003). Both the findings of Ball et al.

During the acute phase (Day 14), H&E staining colon tissue from model animals showed: increasingly

severe inflammatory lesions extensively throughout the colon; significant and complete loss of crypts; surface erosion with exuberant inflammatory exudates; patchy re-epithelization; lamina propria fibrosis with acute and chronic VEGFR inhibitor inflammatory infiltrate; submucosal edema; and mixed inflammatory cell infiltration. In the AG group, mucosa had tightly packed glands with a normal amount of goblet cells (Fig. 3A). The disease severity, scored by the DAI, reached its highest level on Day 8. Fig. 3B shows significant effects of AG on the reduction of the DAI score (p < 0.05). This suppression of the experimental colitis by the herb was not only evident during DSS treatment, but also very obvious after the cessation of DSS administration (i.e., Day 8), suggesting that AG significantly promoted recovery from the colitis. Fig. 4A is a representative macroscopic morphology for the control group, model group, and AG group. Obvious tumorigenesis was observed

in the model group. However, in the AG treatment group, the tumor number and size were significantly less and relative small. Fig. 4B shows representative BAY 73-4506 H&E staining histological sections of the three groups. In the colon tissue from the model animals, multifocal adenomatous lesion was observed, and there was no invasion into submucosa; there was mild inflammation with cryptitis, mild degree loss of goblet cells, fibrosis, and apoptotic changes. For the AG treatment group, mucosa shows tightly packed glands with a normal amount of goblet cells while crypt architecture remained normal. Compared to the model, the histological sections of the AG treatment group are more similar to those FER of the control group. Fig. 4C shows colon carcinogenesis data. Our results showed that compared to the model group, AG treatment very significantly reduced the total number of colon tumors and load of tumors (p < 0.01 and p < 0.001, respectively). Tumor distribution data reflected this reduction, in which the number of large tumors (1–2 mm and > 2 mm) decreased while the number

of small tumors (< 1 mm) increased. Previous studies have shown that blockade of inflammatory cytokines significantly decrease the severity of colitis. To explore mechanisms of inhibition of AOM/DSS induced colitis and tumorigenesis by AG treatment, using an ELISA array, we determined proinflammatory cytokine levels in the colon tissues collected on Day 14. Colonic levels of the proinflammatory cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, IFN-γ, tumor necrosis factor-α, G-CSF, and GM-CSF were markedly elevated in the DSS model group. Treatment with AG significantly inhibited the levels of those 12 cytokines by 44%, 35%, 42%, 39%, 46%, 34%, 37%, 44%, 51%, 40%, 46%, and 37%, respectively (p < 0.05; Fig. 5).

This is most parsimoniously interpreted as selective felling, death of the elm by disease (the well-known elm decline) or perhaps AZD5363 mw a combination of both. Whatever the precise mechanism it created gaps in the oak woodland which could be colonised by hazel and understory shrubs. Cereals (wheat/oats, barley) are present but at low concentrations. In contrast the core from the Yarkhill palaeochannel (YHC4, Section 5) showed continuation of this change in high resolution (over 0.67 m) with woodland changing from the mixed oak-hazel

seen in the other channels (also with pine here) to open grassland with bracken and high cereal levels (wheat/oats and barley). Indeed the cereal pollen concentration is unusually high (Fig. 6; >10% TLP) at levels normally encountered from in or adjacent to arable fields and there are two possible explanations. First that arable cultivation was being undertaken on a tongue of low dryland VX-809 cell line to the east of the palaeochannel and/or the influx was enhanced by aquatic pollen transport from overland flow across arable land. This mechanism has been shown to occur in modern catchments (Brown et al., 2007 and Brown et al., 2008). Either way this clearly indicates initial deposition of the superficial overbank unit co-incidentally with

both deforestation and the expansion of arable farming. Typically there was no organic matter in the superficial silty-sand unit that could be dated using AMS. So in order to determine the chronology of deposition 6 OSL dates were acquired from two

sections. The dates at section 4 (Upper Venn Farm) give a date of initial deposition of 4100 ± 300 BP. There is an inversion in the two upper dates; however, they overlap at the 95% error level. Taken together they conform with the AMS dating from the adjacent Section 5 and suggest a rapid rate of deposition (1–2.4 mm yr−1) during the period 2150 BCE to 620 CE or a little later. Given that there are no discontinuities within this unit this suggests high levels of overbank deposition from the early Bronze Age to the early post-Roman (Saxon) period. The dates Galeterone from section 6 range from 2200 ± 100 BP to 930 ± 100 BP, which given the date from the underling unit suggests accumulation from c. 2340 BCE to 1020 CE, the early Bronze Age to the High Mediaeval period with a slightly lower rate of accumulation of 1.0–1.1 mm yr−1. This may be partly due to the wider floodplain but the longer chronology suggests we have a sediment pulse with reworking or bypassing of upper reaches as alluviation continues (Nicholas et al., 1995). This continuity of sedimentation is supported by the archaeological record from the catchment which shows an abundance of crop-marks, earthworks and occupation sites from the Bronze Age to the post-Roman period (Fig. 6). Indeed there is a cluster of Prehistoric sites in the upper northwest of the basin, which corresponds with the tributary that seems to have produced much of the upper fill of the lower valley.

Musical training also seems to affect the extent of cross-modal integration. In a successful musical performance, stimuli from several modalities have to be processed with high temporal selleck chemicals precision. Audio-visual integration involving tones and lights can be demonstrated even in musically untrained subjects (Elmer et al., 2012). However, the integration of the senses seems to be enhanced by musical training in relevant domains, as shown in increased neural responses

to simultaneous tactile and auditory input in trumpeters (Schulz et al., 2003), increased behavioral sensitivity and cortical responses to audio-visual asynchronies in musicians (Lee and Noppeney, 2011), and increased audiovisual integration in brainstem responses (Musacchia et al., 2007). Also, a recent multimodal training study showed that two weeks of piano training that involved visual, auditory, and sensorimotor modalities resulted in a stronger enhancement of audio-visual integration of stimuli in the posterior part of right STG than training that only involved the visual and auditory domains (Paraskevopoulos et al., 2012; Figure 1). Recent models of multisensory integration in superior colliculus (SC) suggest that integration is achieved by feedback

and feedforward synapses GSK1210151A manufacturer of the unisensory neurons with a multisensory area within the SC (Magosso et al., 2008). While additional

mechanisms and more complex integration might be at work in the cortex, the role of feedforward predictions from one modality to the other, Progesterone and evaluation of corresponding feedback between modalities has also been suggested as an important mechanism for the efficacy of musical training for cortical plasticity (Lee and Noppeney, 2011). Research from animals and computational models indicates that multisensory inputs during development are crucial for the formation of the corresponding neural multisensory integration networks (Cuppini et al., 2011). Conversely, research in blind and deaf humans shows how sensory deprivation leads to functional reorganization of the sensory cortical areas, but that these areas maintain their organizational principles in the process and are probably to a large extent multisensory in nature to begin with (Voss and Zatorre, 2012). From anatomical work, it is furthermore known that even early sensory cortical structures are connected to other sensory and association cortices, and that the auditory cortex receives multisensory thalamic inputs (Budinger et al., 2006; Budinger and Scheich, 2009). These anatomical connections provide a good basis for the assumption that predictions and evaluations via cross-modal feedforward and feedback loops are an important mechanism in multimodal learning such as playing a musical instrument.

, 2012). One way in which these factors affect heteromerization is by affecting the dwell time of specific variants in the ER. However, the significance of ER-assembly mechanisms for AMPARs in neurons (previous work had largely been done in recombinant receptors) and how they might impact synaptic transmission was unknown. Penn et al. (2012) provide evidence that alternative splicing facilitates the regulated assembly of AMPARs and directly modulates synaptic transmission in the CA1 region of the hippocampus. The flip/flop cassette was identified soon buy AZD6244 after the initial cloning of AMPAR subunits and all AMPAR subunits undergo this alternative splicing

(Sommer et al., 1990). Flip/flop has numerous

effects on receptor function including the extent and degree of desensitization, though the specific effect depends on the specific subunit and subunit combinations (Dingledine et al., 1999). In the Selleckchem Kinase Inhibitor Library present study, the authors investigated the role of the flip/flop cassette in the hippocampus and found that chronic deprivation of activity by the Na+ channel blocker tetrodotoxin (TTX) decreased the ratio between flip/flop splice variants for GluA1 and GluA2 in the CA1 but not CA3 regions. These effects were reversed upon removal of TTX highlighting the dynamic nature of these actions. Importantly, the authors also found a difference in the subunit-specific turnover rate from flip-to-flop with the rate being more rapid for GluA1 (τ = 2.4 hr) than for GluA2 (τ = 4 hr). The relatively fast increase in GluA1o subunits

combined with a longer dwell time of GluA2i subunits in the ER (Greger et al., 2002) contributed to the formation of more GluA1o/GluA2i receptor complexes. Further the authors show that the GluA1o isoform more readily recruits GluA2i to form heteromeric complexes than that of GluA1i. Hence, because of differential rates of alternative splicing, the longer Glyceronephosphate O-acyltransferase dwell time of GluA2 in the ER, and the preferential assembly of specific subunit variants in the ER into heteromers, GluA1o/GluA2i becomes a more prominent AMPAR in CA1 pyramidal neurons with activity depravation. But what makes GluA1o/GluA2i heteromeric receptors so distinctive? GluA1o/GluA2i heteromers show less desensitization and recover faster from desensitization than that of other GluA1/GluA2 splice variant combinations. The authors show that following TTX treatment, surface AMPARs from CA1 pyramidal neurons showed properties consistent with a GluA1o/GluA2i composition, an effect apparently not dependent on accessory proteins. Of course, the coup de grace is that the authors demonstrate that synaptic inputs to CA1 pyramidal neurons show greater fidelity in response to high frequency stimulation—presumably due to the reduced desensitization properties of GluA1o/GluA2i.

6 μg/ml), KU-57788 cost in 0.1% bovine serum albumin in 0.1 M Tris saline (pH 7.6) for 1 day at room temperature and an additional 3 days at 4°C. The primary antibodies were visualized by the immunoperoxidase method. Sections were analyzed on a Tecnai Biotwin transmission electron microscope (FEI) equipped with an AMT digital camera. Profiles were identified by the morphological

criteria as previously described (Peters et al., 1991). For the quantitative analysis, ten random nonoverlapping micrographs (36 μm2 per micrograph) were taken from the tissue-plastic interface of stratum radiatum of the dorsal hippocampus of each animal (n = 3 per condition). Cultured rat astrocytes and rat hippocampal brain slices were used for western blotting. Cells and brain slices were homogenized using lysis buffer containing the following: 100 mM Tris (pH 7.0), 2 mM EGTA, 5 mM EDTA, 30 mM NaF, 20 mM sodium pyrophosphate, and 0.5% NP40 with phosphatase and protease inhibitor cocktail (Roche). The homogenates

were then centrifuged at 13,000 × g (20 min, 4°C) to remove cellular debris, and then protein concentrations of the crude GDC-0449 ic50 lysates were determined by performing a Bradford assay with the DC Protein Assay dye (Bio-Rad). The protein samples were diluted with 1× Laemmli sample buffer and boiled for 5 min. After SDS/PAGE, proteins were transferred to PVDF membranes, blocked in 5% milk for 1 hr at room temperature, rinsed with Tris-buffered saline with 0.1% Tween 20 (TBST) and incubated else with mouse anti-sAC monoclonal antibody (R21, 1:2,500) overnight at 4°C. After four washes with TBST, the membranes were incubated with the anti-mouse secondary

antibody conjugated to horseradish peroxidase (1:10,000) for 1 hr at room temperature. The membranes were then washed three to four times (15 min) with TBST, and bands were visualized using enhanced chemiluminescence (ECL, Amersham Bioscience). Total RNAs were extracted from hippocampal brain slices and cultured astrocytes using TRIzol reagent (GIBCO-BRL) and were subjected to DNase I treatment and complementary DNA synthesis was carried out using M-MLV reverse transcriptase (GIBCO-BRL). Reverse transcriptase was omitted as a negative control. PCR primers (Pastor-Soler et al., 2003) are all intron spanning and sequences and expected product sizes are as follows: sAC sense 5`-CATGAGTAAGGAATGGTGGTACTC-3`; antisense 5`-AGGGTTACGTTGCCTGATACAATT-3` (110 bp); β-actin sense 5`-GTGGGGCGCCCCAGGCACCA-3` and antisense 5`-GTCCTTAATGTCACGCACGATTTC-3`(526 bp). Primers used to amplify sAC splice variants were as follows: sAC; i.e., from exons 1 to 5: sense 5`-ATGAGTGCCCGAAGGCAGGAATTACAG-3` antisense 5`-TGCTCTCTGATCCG GAATCCT-3`; sACt from sACfl splice variants; i.e., from exons 9 to 13: sense 5`-TGCAAACCCACTGCTTGCTTGC-3` antisense 5`-ACTCGGCTGCAGTTCGTCA T-3`; sACsomatic, which starts at the alternate promoter upstream from exon 5; i.e.