p. injections of saline. During the withdrawal period, the rats were orally administered KRGE (20 mg/kg/d or 60 mg/kg/d) dissolved in distilled water (DW) or only DW once/d for 3 d (Fig. 1B). Thirty min after the third dose of KRGE, the rats were tested for anxiety-like behavior in an elevated plus maze (EPM) to evaluate the possible

anxiolytic effects of KRGE during EW. Immediately after the EPM test, each rat was decapitated and the entire brain was removed and stored at −80°C. Tissue samples from the CeA and VTA were punched out for neurochemical analyses; coordinates for the CeA [anterior-posterior (AP) = −2.0 mm, medial-lateral (ML) = −4.2 mm, dorsal-ventral (DV) = −7.8 mm) and VTA (AP = −6.0 mm, ML = −0.7 mm, DV = −7.8 mm) were based on the Paxinos and Watson rat brain atlas [7] and [15]. At the same time, blood samples were collected for a radioimmunoassay Navitoclax molecular weight (RIA) of corticosterone (CORT) levels. The EPM (Shanghai Yishu Co., Shanghai, China) consisted of a plus-shaped maze that was elevated 50 cm above the ground and equipped with a video tracking system. Each of the four arms was 40 cm long × 10 cm wide; two of the opposing arms were enclosed by 30 cm high black wooden walls (closed arms) whereas the

other two opposing arms were devoid of walls (open arms). The EPM test is thought to induce anxiety due to the natural fear of open and elevated spaces that exists in rodents. The number of entries

into open arms and the time spent in open arms are negatively correlated with the OSI-744 clinical trial anxiety level of the rat. Thirty min after the third dose of KRGE, all rats were individually subjected to the EPM test as described previously MycoClean Mycoplasma Removal Kit [7]. Briefly, without any pretest handling, each rat was placed in the center of the maze, after which the cumulative time spent in each arm and the numbers of entries into the open or closed arms were recorded during a 5 min test session. The percentage of time (T) spent in open arms was calculated as follows: PercentageofTspentinopenarms=Tspentinopenarms(Tspentinclosedarms+Tspentinopenarms). Approximately 1.5 mL of blood collected from each rat was mixed with EDTA (20 mg/mL, 20 μL) and centrifuged (1,000 × g) at 4°C for 10 min. The plasma was separated out and CORT was measured using an ImmuChem double antibody 125I RIA kit (MP Biomedicals, Orangeburg, NY, USA) with the values expressed as ng/mL [7]. To determine the involvement of amygdaloid DA receptors in the expected anxiolytic effects of KRGE during EW, another set of experiments was conducted using the same EW schedule described above, in which the rats were given an intra-CeA infusion of either a D1R antagonist (SCH23390) or a D2R antagonist (eticlopride) 5 min prior to the third dose of KRGE (60 mg/kg). These rats were also tested in the EPM. All rats were placed under anesthesia (sodium pentobarbital, 50 mg/kg, i.p.

An SRT1720 supplier increase in islands and lateral sand bars in the reach is also shown in Fig. 5C. Analysis indicates that the reach gained 23,600 m2 of island area in 40 km of reach (the length of the reach is limited by the extent of the aerial photos). The areal extent of island area in 1999 was 150% greater

in 1950. Additionally, the island morphology has shifted from in-channel islands (indicative of the pre-dam river) to large islands attached to the outside of meander bends with distinctive distributary channels running through them. These are essentially former islands that have become attached to the banks as a result of excess sediment cutting off side channels. The Reservoir-Dominated find more Interaction reach is located 140–190 km downstream from the Garrison Dam. Reservoir effects vary both annually and seasonally due

to changing reservoir levels creating a recognizable deltaic morphology. The Reservoir-Dominated Interaction reach is characterized by aggrading islands, sand bars, and the flooded meander bends (former meanders that have been flooded by the reservoir). 9 of 11 sites indicate deposition greater than the natural variability (269 m2). Fig. 4A is typical of cross sections in this area and shows al decrease in cross-sectional area of 411 m2. No suitable historic aerial imagery was available for this section of the river but current conditions indicate higher levels of low elevation sand bars than other sections of the river. The active extent of this reach can migrate drastically

from year to year depending on the reservoir level (as much as 160 km longitudinally, Fig. 6). Although the 50 km reach encompasses most of the delta in a typical discharge year, changes in releases from either dam can substantially change the active extent of the reach. Consequently, the depositional morphology and ultimately the Reservoir-Dominated Interaction reach can have a broader spatial distribution (Fig. 6A and B) than can be accounted for by a single year (insets A1 and A2, B1 and much B2). Although the lake level and backwater effects are highly spatially and temporally variable, the most recent set of aerial photos indicate the area of maximum deposition encompasses only this 50 km section of river. The morphology of this reach changes with varying lake levels. Islands, flooded meander scrolls, and deltaic splays are alternatively exposed and flooded. A large numbers of dead trees from flooding and those washed downstream litter the landscape and are present in channel. The Reservoir reach (Lake Oahe) is remarkably stable. This reach extends from approximately 190 km to just upstream of the Oahe Dam; 512 km downstream from Garrison Dam. Cross-sections in this section extend into the first 100 km into this reach. All 12 cross sections in the Oahe reach shows deposition greater than natural variability from 1963 to 1989 (269 m2).

There were selleck inhibitor also rice grains and phytoliths, acorns, oyster shells, and the bones of dogs, pigs, and other animals ( Zhong et al., 2007). Subsequent research farther inland at Yangshan Cave has also yielded wild rice belonging to the Kuahuqiao period and some

traces in the Sangshan period, dated to about 10,000 cal BP. Interestingly, many pottery sherds of the Sangshan period were tempered with plant remains, including some rice husks ( Zhao, 2011). The site of Jiahu (9000–7800 cal BP), on the Upper Huai River about midway between the Yangzi and Yellow rivers, was the first early and well-documented example of a substantial settled village with rice farming. Jiahu covers some 50,000 m2 and includes residential areas, manufacturing areas, and cemeteries in orderly array. Charred plant remains recovered from soil samples represent a broad suite of lotus roots, acorns, Trapa nuts, rice, soybean (Glycine max), and other edible plants. Wild species gathered locally clearly dominated the local diet at Jiahu, but because the site lies beyond the known distribution of wild rice, it is evident that the rice consumed in the village was cultivated there ( Liu et al., 2007). Surprising

evidence of rice fermentation at Jiahu ( McGovern et al., 2004) further illustrates this website the importance of rice to Early Neolithic cultures, regardless of its domestication status. Recovered bones represented about 20 animal species, among which dog was the only domesticate, and almost all the trash pits contained fish bones ( Zhao, 2011). The Jiahu community Avelestat (AZD9668) was supported primarily by the hunting, fishing, and gathering of wild plants and animals, but it represents the kind of geographical circumstances in which the transition was made from hunting-gathering to wet-rice farming in China, and within which endlessly replicated infrastructures

of villages, dams, ditches, and other features would come to exemplify the engineering of a major new human ecological niche. It is clear that China’s Central Plain (Fig. 1), the vast alluvial lowland laid down by the annual flooding of the Yellow River in the north and the Yangzi River in the south, and extending deep inland from the Pacific Coast to the Qinling Mountains, was the heartland of grand-scale agricultural development in China and the great economic engine of its sociopolitical growth. Millets (both foxtail Setaria italica and broomcorn Panicum miliaceum) and other dryland grains of generally northern origins were cultivated there, and so was rice, a plant native to the alluvial subtropical wetlands of the region. For many decades research into the origins and development of Chinese civilization focused on north China’s Middle Yellow River Valley, including its small tributary, the Wei River Valley, where the modern city of Xi’an is located.

6 to 249 km2. During the Last Glacial Maximum and up to about 10,000 years ago, the four northern Channel Islands (San Miguel, Santa Rosa, Santa Cruz, and Anacapa) were connected into a single landmass known as Santarosae Island, separated from the mainland by a watergap of about 7–8 km (Erlandson et al., 2011b). This separation from the mainland led to distinct island ecosystems and numerous endemic and relict species. In general, the biodiversity of terrestrial plants and animals is reduced compared to the mainland, with the largest post-Pleistocene land mammals being the

diminutive island fox (Urocyon littoralis) found on six islands and the island spotted skunk (Spilogale gracilis) found on two islands. Only Peromyscus maniculatus (island deer mouse) is found on all eight of the Channel MEK inhibitor Islands. Deer, elk, and large to medium sized predators common on the mainland were all absent from the islands, until some were introduced during the historic period. Terrestrial plants were also less diverse than the mainland, with a Ulixertinib ic50 smaller amount of oak woodland and other plant communities. Freshwater was limited on some of the islands, but the large islands of Santa Cruz, Santa Rosa, Santa Catalina, and San Miguel are all relatively well watered. Our perspective of both island

plant communities and freshwater availability, however, is changing as the islands recover from more than a century of overgrazing from introduced livestock and both freshwater and terrestrial plants appear to have been more

productive than once presumed. Although ethnobotanical research has been limited on the islands, recent research demonstrates the exploitation of blue dick corms and other plant foods throughout the Holocene ( Reddy and Erlandson, 2012 and Gill, 2013). Humans colonized the northern islands by at least 11,000 B.C., while the northern islands find more were still one landmass and there were more conifers and other trees scattered around the islands. Native Americans appear to have lived on the islands more or less continuously until about A.D. 1820, when they were removed to mainland missions. Following Native American occupation, the islands were occupied sporadically by Chinese abalone fishermen with the ranching period beginning in the mid-19th century. Today, the northern Channel Islands and Santa Barbara Island comprise Channel Islands National Park, while San Nicolas and San Clemente have naval installations, and Santa Catalina is privately owned with the only formal city (Avalon) on the islands. Each of these human occupations had different influences on island ecosystems, with distinct signatures that help inform contemporary environmental issues, conservation, and restoration. Population growth is one of the key factors related to increased human impacts on ecosystems.

In such circumstances, they may develop the illusion that they are becoming better at the task and able to persuade others that this is so. In the financial domain, this would have clear implications for people’s selection of investment strategies. This research was supported by a scholarship awarded by the Responsible Gambling Fund to Juemin Xu. We thank Peter Ayton for Staurosporine cost invaluable comments on earlier drafts of the manuscript. “
“The processing of a word in a sentence is affected by a range of linguistic properties, across many tasks and experimental

paradigms, but how does the cognitive system change the way it responds to these properties in different tasks? Two hallmark effects derive from the frequency of a word to be Trichostatin A mw processed (high frequency words are processed more quickly than low frequency words) and the predictability of a word in its sentence context (more predictable words are processed more quickly than less predictable words; see Kutas and Federmeier, 2011, Rayner, 1998 and Rayner, 2009 for reviews). While frequency

and predictability effects are robust and well documented, the magnitudes of these effects vary across tasks and paradigms (even when equating the magnitude of the frequency or predictability manipulation). The fact that these effects change across tasks suggests that the way in which people approach a task can modulate the extent to which they are sensitive to specific linguistic properties of the words they read (even when held constant across tasks). In the present study, we investigated this cognitive flexibility in reading for comprehension and proofreading. While still poorly understood, proofreading is a useful task for elucidating how cognitive processing changes along with task demands because Ribose-5-phosphate isomerase of its similarity to reading for comprehension in

terms of stimuli and response measure. The only differences in experimental design between these two tasks are the instructions and the inclusion of sentences that contain an error. Thus, we can study how processing of sentences without errors changes when people are asked to process them in different ways: checking for errors or reading for understanding. In the remainder of this introduction, we briefly discuss frequency effects and predictability effects and existing evidence regarding how they change magnitude across tasks, then turn to theoretical and empirical aspects of proofreading and discuss the goals and design of the present study.

Fluvial process dynamics in stable alluvial channels includes a broad range of interacting processes that mobilize, transport, erode, and deposit sediment—and create, maintain, and degrade

riparian habitat. One significant aspect of this range of fluvial processes that is altered by incision affects the way channels interact with their floodplains, or lateral connectivity (Brierly et al., 2006) that includes GPCR & G Protein inhibitor transfer of water, sediment, nutrients, organic matter, and biota between the channel and adjacent floodplain (Pringle, 2001, Pringle, 2003 and Brookes, 2003). Heterogeneous channel-floodplain dynamics related to connectivity result in biocomplexity that is lost as incision disconnects floodplains (Amoros and Bornette, 2002), leaving the former floodplain abandoned as a terrace alongside the channel. Dynamics in incised alluvial channels include processes such as bank erosion, selleck chemicals llc which is part of a sequence of events that follows channel incision and increases in bank height or bank angle. In incised channels, banks may reach a critical threshold height where any increase in channel bed lowering that increases bank height may in turn cause bank erosion (Carson and Kirkby, 1972 and Thorne, 1982). Both widening and channel

narrowing have been reported following incision in alluvial channels. In the case of widening following incision, as bank angles lessen during mass wasting and bank retreat, another threshold may eventually be reached where at a given bank height the low angle surface is stable enough to support pioneer woody plants (Simon, 1989). Conceptual models describe the relation between incision

and bank erosion as following a series of steps in a sequence of adjustment (Schumm et al., 1984, Simon and Hupp, 1986, Simon, 1989 and Doyle et al., 2003). Steps after initial incision may Urease include: increased bank height and isolation of the former floodplain as a terrace, bank erosion, channel aggradation and creation of a new lower bank angle and height, and eventual formation of a new stable channel with a correspondingly lower inset floodplain that can support riparian vegetation establishment (Simon, 1989); a sequence of adjustments estimated to take hundreds to thousands of years (Simon and Castro, 2003). However, one conceptual model does not explain the variation in evolutionary pathways or rates in various environments (Doyle et al., 2003 and Beechie et al., 2008). In fact, numerous recent studies suggest that narrowing follows incision, often in association with embankments and erosion control structures (Surian, 1999, Łajczak, 1995, Winterbottom, 2000, Rinaldi, 2003 and Rădoane et al., 2013). Moreover, some rivers progress through a sequence of changes that includes spatial differences with respect to narrowing and incision followed by widening and aggradation (Surian and Cisotto, 2007). Steiger et al.

Fig. 3 and Table 1 depict that the IC50 values markedly decreased with the addition

of SG to epirubicin and paclitaxel. The IC50 value of epirubicin in the HeLa cells was 1.05 μg/mL, which decreased to 0.15 μg/mL with the addition of 80 μg/mL SG. This result indicates that a subtoxic concentration of SG significantly increases the cytotoxic efficacy of epirubicin. SG exhibited similar IWR-1 in vitro potentiating activities on paclitaxel in all three cancer cell lines. To examine whether the role of SG in the cytotoxic effect of epirubicin and paclitaxel was caused by the enhanced apoptosis, we assessed the resulting apoptosis in the HeLa cells after separate treatments with epirubicin and paclitaxel alone and after the treatment with the combination of SG and the two drugs. The stage of apoptosis was determined through annexin-V analysis. As shown in Fig. 4A and C, the percentage of apoptotic cells was considerably higher in the cotreated cells than in the epirubicin- and paclitaxel-treated cells. To determine the activation MEK inhibitor of caspase in the cells, we detected the PARP cleavage through immunoblotting analysis.

Fig. 4B and D show that PARP was cleaved to yield an 85-kD fragment in the drug-treated cells and that the amount of the cleaved 85-kD fragment was more significant in the co-treated cells than in the epirubicin- and paclitaxel-treated ADAM7 cells. On the basis of these results, we suggest that SG enhances the anticancer activities of epirubicin and paclitaxel through caspase-associated apoptosis. To elucidate the initiation event of apoptosis, we inspected the activation kinetics of the two initiator caspases, namely, caspase-8 and -9, and the effector caspases, caspase-3/-7. As shown in Fig. 5,

the activities of caspase-9 and -3/-7 greatly increased in the cotreated cells than in the epirubicin- and paclitaxel-treated cells. By contrast, the activity of caspase-8 did not show any change in all cells. We then determined the cleavage of caspase-9 and -8. Specifically, we examined the proteolytic activation of these caspases through immunoblotting analysis. Apparent cleavage was observed in caspase-9 but not in caspase-8. The amounts of the active form of the cleaved caspase-9 were higher in the cotreated cells than in the epirubicin- and paclitaxel-treated cells. The data suggest that epirubicin and paclitaxel-induced apoptosis might be potentiated by SG via the intrinsic apoptosis pathway in HeLa cells. The release of mitochondrial cytochrome c is the crucial event in caspase-9 activation [40]. The family members of the Bcl-2 family, namely, Bax and Bak, serve as an essential gateway for the release of cytochrome c [5] and [41]. Fig.

94 ± 0.06, 0.95 ± 0.05, and 0.97 ± 0.04 times scrambled siRNA14, respectively (p > 0.05, ANOVA; Figures 4A and 4B). In stark contrast, expression of siRNA14 together with the TSPAN7ΔC variant resistant to siRNA14 (rescue ΔC) did not reverse the reduction in the expression of GluA1, GluA2/3, and PSD-95 caused by TSPAN7 silencing. Specifically, staining intensities for GluA1, GluA2/3, and PSD-95 were 0.79 ± 0.06 (∗p = 0.027), 0.71 ± 0.06 (∗∗p = 0.008), and 0.80 ± 0.03 (∗∗p = 0.002) times that of scrambled siRNA14, and cluster densities SCH727965 solubility dmso for GluA1, GluA2/3, and PSD-95 were 0.70 ± 0.05 (∗∗p = 0.004), 0.65 ± 0.07 (∗p = 0.013), and 0.75 ±

0.05 (∗∗∗p < 0.001, ANOVA) times that of scrambled siRNA14, respectively (Figures 4A and 4B). Expression of siRNA14 together with either rescue WT or rescue ΔC had no effect on GluN1, β1 integrin, or Bassoon expression (Figures 4A and 4B, and data not shown). To further probe TSPAN7's role in synapse development, we examined whether TSPAN7 knockdown prevented thrombospondin-1 (TSP-1)-induced synaptic maturation

Ponatinib order (Christopherson et al., 2005). Immature hippocampal neurons (DIV8) transfected with scrambled siRNA or siRNA14 were treated for 12 days with TSP-1, and effects on synapse density were assessed in terms of colocalization of synapsin and PSD-95 (Garcia et al., 2010). Scrambled siRNA14 neurons treated with TSP-1 had significantly higher levels of synapsin/PSD-95 colocalization than control untreated

neurons (Figure S4, colocalized clusters per 50 μm dendrite: 23.94 ± 2.64 for scrambled siRNA14 treated versus 17.45 ± 1.32 for scrambled siRNA14 untreated; ∗∗p < 0.01). By contrast, in TSPAN7-silenced neurons, the colocalization of synapsin and PSD-95 was modestly but significantly reduced under basal conditions (colocalized clusters per 50 μm dendrite: 12.84 ± 0.66 for siRNA14 untreated versus 17.45 ± 1.32 for scrambled siRNA14 untreated, ∗p < 0.05), and unaffected by TSP-1 treatment (15.44 ± 2.33 for siRNA14 treated versus 12.84 ± 0.66 for siRNA14 untreated, p > 0.05; Figure S4). These findings are further evidence that TSPAN7 is required for synapse maturation, and are consistent with the Methocarbamol observed reduction in spine head size when TSPAN7 is knocked down; they also indicate that the C terminus of TSPAN7 is involved in synapse maturation. Having demonstrated morphological and molecular changes caused by TSPAN7 silencing, we next investigated whether TSPAN7 affected excitatory synaptic transmission by recording spontaneous miniature excitatory postsynaptic currents (mEPSCs) in primary hippocampal pyramidal neurons. We took advantage of the low transfection efficiency in primary neuron cultures and restricted the electrophysiological recordings to transfected neurons surrounded only by nontransfected cells. Thus, the patched neuron received synaptic inputs from control cells expressing normal levels of TSPAN7.

This study also demonstrated a suppression of cortisol release by the NK1R antagonist during cue/stress exposure, suggesting a role of the NK1R in regulation PLX4032 in vivo of stress-induced HPA axis function, as mentioned above. Finally, these findings

were complemented by neuroimaging data, which showed that NK1R antagonist administration potently blocked activation of stress-responsive neurocircuitry after presentation of strongly aversive visual stimuli. Subsequent genetic analyses have suggested an association of specific haplotypes within the TacR1 locus, which encodes the NK1R, with increased risk for alcohol dependence ( Seneviratne et al., 2009). Genetically defined subgroups of patients may therefore be particularly responsive to NK1R antagonism. NPS is a 20 amino acid peptide identified as the endogenous ligand for the deorphanized GPR 154, currently named the NPS receptor (NPSR) (Xu et al., 2004). In situ hybridization studies have shown that NPS precursor mRNA is expressed in about 500 cells localized only in three brainstem regions: the peri-LC area, the principal sensory trigeminal nucleus, and the lateral parabrachial nucleus (LBP) (Figure 3; Liu et al., 2011; Xu et al., 2007). Bortezomib order A dense hypocretin/orexin fiber network surrounding NPS-positive cells has been described, suggesting the possibility of crosstalk between these two neuronal populations (Liu et al.,

2011). NPSR is Gq/Gs coupled, and its activation by NPS induces mobilization of Ca2+, stimulates cAMP synthesis, and increases cellular excitability (Meis et al., 2008; Reinscheid and Xu, 2005; Xu et al., 2004; Yoshida et al., 2010). In contrast to the anatomically restricted expression of the NPS transcript, NPSR is widely expressed in the brain, including olfactory regions, the AMG complex, and other limbic structures (Leonard and Ring, 2011; Liu et al., 2011; Xu et al., 2007). The widespread distribution of the NPSR and its mRNA in the brain indicate that the NPS system may be important

in regulating a variety of physiological functions. Activation of NPSR results in an unusual behavioral profile. On one hand, it has been shown that NPS activates arousal and stress-responsive mechanisms (Smith et al., 2006). Accordingly, and similar to CRF and other stress mediators, NPS potently GPX2 decreases palatable food intake or feeding elicited by partial restriction (Beck et al., 2005; Cifani et al., 2011; Peng et al., 2010; Smith et al., 2006). However, additional studies have shown that NPS also activates the hypothalamic hypocretin/orexin system (Cannella et al., 2009; Kallupi et al., 2010; Niimi, 2006) and facilitates home-cage food consumption (Niimi, 2006). Unusually, the proarousal and prostress properties of NPS are combined with potent anxiolytic-like actions (Jüngling et al., 2008; Leonard et al., 2008; Rizzi et al., 2008; Vitale et al., 2008).

In addition, the positivity of the test was analysed in two ways: by the global animal status (the animal as a whole) as well as by the individual organ status (each separate organ of the animal). The tissue sections were also evaluated in order to search for possible anti-T. gondii antibody cross reactions with other parasites.

McNemar’s test was used to compare the results obtained by IHC. The tissue samples from the liver, heart and brain of the evaluated animals (the individual organ status) were compared to the global animal statuses. A Fisher’s Exact Test was used to determine the association between the IHC positive and negative results in the different organs (liver, heart and brain) and the different T. gondii titres obtained by the MAT in all 26 seropositive DAPT mw animals. The animals were separated into two groups based on their titres: 1:25 to 1:50 and 1:100 to 1:3200. Fisher’s Exact Test was used for the comparative analyses between the two titration groups (1:25 to 1:50 versus 1:100 to 1:3200) and the immunohistochemical detection of T. gondii (positive or negative) in the samples from the brain, liver and heart, in order to identify the most suitable organ to detect infected animals even presenting low titres. In addition, the Chi-square test

was used to compare the animals that tested positive by IHC with their respective titres obtained by the MAT. This test was used to determine Selleckchem Hydroxychloroquine if there was an association between the titration at which the animal was seropositive for T. gondii and positive by IHC. The Statistical Package for Social Science (SPSS) version 12.0 software was used. Differences where P < 0.05 were considered significant. The serological results are presented in Table 1. The most frequent titres obtained were 1:50 (34.6%), followed by 1:25 (19.2%), 1:400 (15.4%), 1:3200 (11.5%), 1:100

(7.7%), 1:200 (7.7%), and 1:800 (3.8%). The histopathological changes in the brain, liver and heart consisted of mild-to-moderate congestion, focal polymorphonuclear inflammatory infiltrate and multifocal or focal mononuclear inflammatory infiltrate. Hepatic vacuolar degeneration, portal fibrosis and necrosis were also observed. The lungs presented Cediranib (AZD2171) thickening of the alveolar septa, atelectasis and pulmonary emphysema. T. gondii cysts were not observed in the H&E-stained histological sections. However, Sarcocystis spp. were identified in the histological sections from both the heart and diaphragm tissues of 88.5% (23/26) of the animals. These cysts were round in shape, variable in size and were widely dispersed throughout the tissues. No significant histopathological changes were found in the other evaluated organs. A total of 46.2% (12/26) of the animals evaluated were positive for T. gondii by IHC in at least one organ distributed as follows: 15.4% (4/26) had parasites only in the liver, 15.4% (4/12) in heart and liver, 7.7% (2/26) in brain and liver, 3.8% (1/26) only in the heart and 3.