Prehistoric animals likely did not attain significantly greater d

Prehistoric animals likely did not attain significantly greater depths; dinosaur burrows, for example, were long unrecorded, and the single example known ( Varricchio et al., 2007) is not much more than 20 cm across and

lies less than a metre below the palaeo-land surface. Plant roots can penetrate depths an order of magnitude greater, especially in arid regions: up to 68 m for Boscia truncata in the Kalahari desert ( Jennings, 1974). They can be preserved as rootlet traces, generally through diagenetic mineral precipitation or remnant carbon traces. Roots, though, typically infiltrate between sediment grains, limiting the amount of sediment displacement and hence disruption to the rock fabric. Alectinib At a microscopic level, too, there is a ‘deep biosphere’ composed of sparse, very slowly metabolizing microbial communities that can exist in pore spaces and rock fractures to depths of 1–2 km (e.g. Parkes et al., 1994). These may mediate diagenetic reactions where concentrations

of nutrients allow larger populations (such as the ‘souring’ of oil reservoirs) but otherwise leave little trace in the rock fabric. Very rarely, these communities have been found to be accompanied by very deep-living nematode worms (Borgonie find more et al., 2011), but these seem not to affect the rock fabric, and we know of no reports of their fossil remains or any traces made by them. The extensive, large-scale disruption of underground rock fabrics, to depths of >5 km, by a single biological species, thus represents a major geological innovation (cf. Williams et al., 2014). It has no analogue in the Earth’s 4.6 billion year history, and possesses some sharply distinctive features: for instance, the structures produced reflect a wide variety of human behaviour effected through tools or more typically mechanized excavation, rather than through bodily activity. Hence, the term ‘anthroturbation’ (Price et al., 2011; see also Schaetzl

and Anderson, 2005 for use in soil terminology) is fully justified, and we use this in subsequent description below. This is extensive, Casein kinase 1 and distantly analogous to surface traces left by non-human organisms. It includes surface excavations (including quarries) and constructions, and alterations to surface sedimentation and erosion patterns, in both urban and agricultural settings. Its nature and scale on land has been documented (e.g. Hooke, 2000, Hooke et al., 2012, Wilkinson, 2005, Price et al., 2011 and Ford et al., 2014) and it extends into the marine realm via deep-sea trawling (e.g. Puig et al., 2012) and other submarine constructions. Here we simply note its common presence (Hooke et al.

Two participants had to be excluded from further analyses because

Two participants had to be excluded from further analyses because of poor data quality. Reaction times and accuracy of task-performance were measured for the behavioral analysis. Reaction times were collected within their individual 95% confidence interval. The power of oscillatory activity was

investigated by convolving the EEG signals with Morlet wavelets (Herrmann et al., 2005). The wavelet transform was performed for each OTX015 individual trial, and the absolute values of the resulting transforms were averaged. This measure of signal amplitude in single trials reflects the total activity for a certain frequency range. In the present study, we computed the power (μV2) of oscillatory activity. We confined the alpha activity to the frequency range from 8 to 12 Hz. Since it has been demonstrated that participants differ considerably in their “IAF” (Klimesch, 1999), the frequencies used in the wavelet analyses of alpha activity were determined individually for every participant. We employed a wavelet family with 7 as its constant ratio (Tallon-Baudry et al., 1997). In the case of 10 Hz, this yields a wavelet

duration of 222.8 ms and a spectral bandwidth of 2.9 Hz around its central frequency. In the present study, the mental state of sustained attention, before the onset of the probe digit, Vemurafenib was the main target to analyze. We principally focused on assessing EEG signals particularly in the period prior to the presentation of the probe digit. In such a prestimulus period, there was no stimulus-locked or event-related activity, so we conducted a frequency analysis, rather than an evoked potential analysis, in the prestimulus period. However, we performed additional event-related potential (ERP) analysis during the poststimulus period. For the total alpha activity, we computed the mean power in the time window from 800

to 200 ms prior to stimulus onset in each frequency range. This time window was chosen to avoid the temporal smearing of poststimulus activity into the prestimulus period. Within this time window, IAFs were obtained from the frequencies showing maximal eltoprazine power of each task in the alpha band on the electrodes P3, Pz, and P4. The range of the IAF across the participants was 8–12 Hz. No baseline correction was applied to the total alpha power, since the total alpha power in a prestimulus period would vanish after a baseline correction. Since the prestimulus alpha power was most pronounced around the parietal region during the sustained attention period (Fig. 2), we selected three electrodes representing parietal brain areas (i.e., P3, Pz, and P4) for further analysis. To make 3-D scalp distributions, as shown in Fig. 2B, source-localization software (sLORETA, version 20081104, The KEY Institute for Brain-Mind Research, Switzerland) was employed in the present study (Lehmann et al., 2012 and Pascual-Marqui, 2002).

As shown

As shown learn more in Fig. 2A–C, the control levels of TEWL and TWF were both affected with the water flux into the skin increasing and water efflux out of the skin increasing in direct proportion to the degree of tape stripping. Similarly, the ER of the pig skin showed a progressive fall in response

to the number of strips taken as the resistivity of the skin sample decreased. For example, the initial batch of 5 tape strips resulted in a highly significant (p < 0.0001) 1.7-fold decrease in ER, when compared with the “control” and a highly significant (p < 0.0001) 3.5-fold increase in TEWL. Following ten tape strips, TWF increased 3.5-fold (p < 0.001), ER decreased 2.4-fold (p < 0.0001) and TEWL increased 5-fold (p < 0.0001) when compared to the unstripped control group. The trend continued with 15 tape strips

resulting in 5.8-fold increases (p < 0.0001) in TWF, 3.3-fold decreases in ER (p < 0.0001) and 5.8-fold increases in TEWL (p < 0.0001) above control. The final ER and TEWL measurements following 20 tape strips, which probably results in the complete removal of the stratum corneum, gave 4.5-fold decreases (p < 0.0001) and 8.1-fold increases ZD6474 mw (p < 0.0001) compared with control, respectively. With the exception of TWF measurements following ten tape strips (p < 0.001), each batch of five tape strips resulted in a highly significant (p < 0.0001) change in the three integrity measurements when compared with the control (0 strips) value. Further investigation into the effect of individual tape stripping after the first 5 strips reinforced the sensitivity of ER in detecting initial membrane damage following the 5 tape strips and then each subsequent individual Tolmetin tape strip thereafter. As shown in Fig. 3A, the ER value following 5 strips decreased

1.5-fold when compared to the “control” after which there was a small, but observable, further fall in ER of the skin membrane with each subsequent tape strip up to 14 strips. At this point there was an overall 3.4-fold decrease in ER (p < 0.0001) when compared to the “control”. The individual strip data correlated well with the grouped 5 tape strip data for ER shown in Fig. 2A–C. TEWL measurements following 5 tape strips, as shown in Fig. 3B, demonstrated a 4.8-fold increase in water efflux from the compromised skin when compared to the ‘control’ which was broadly comparable to the batches of 5 strips. However, TEWL measurements following each subsequent individual tape strip did not show a uniform pattern of increased damage as assessed by water efflux.

This is further supported by recent studies that demonstrated col

This is further supported by recent studies that demonstrated colorectal adenocarcinomas characterized by the BRAF V600E mutation have significantly worse overall survival when compared to BRAF wild-type or KRAS mutated adenocarcinomas C646 concentration [3], [14], [15] and [16]. Additionally, SSA/Ps have been reported to be of higher risk of progression [17] and [18]. Our study attempted the further investigation of underlying molecular alterations in serrated colorectal polyps through gene expression profiling. In validation studies, we employed quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and routine immunohistochemical

techniques available in most pathology laboratories using samples from surgical resections and polypectomies. We have identified claudin-1 (CLDN1) as significantly upregulated in polyps bearing the BRAF V600E somatic mutation both on a gene expression level and a protein level, regardless of polyp type. Our results indicate that CLDN1 up-regulation occurs early in the development of SSA/P and its overexpression in a proportion of MVHP suggests a close relation between these two

lesions of the serrated pathway. Polyp samples used in microarray gene expression profiling and qRT-PCR were obtained from surgical resection specimens. The fresh resection specimens were examined and sampled in a hospital immediately after resection or in the pathology laboratory within 30 minutes of resection. Each polyp was divided into equal portions. Portions were either immediately snap-frozen in liquid nitrogen or Volasertib datasheet formalin fixed and paraffin embedded RVX-208 (FFPE). The frozen

sections selected for the study were further verified histologically before analysis. The diagnostic criteria for SSA/P and MVHP are based on published criteria relying mainly on polyp architecture [9]. The architectural features assessed included crypt branching, horizontal dilatation of basal crypt compartments, and presence of serration at the base of the crypts. Polyps were classified as SSA/P when at least two of these features were present, and only lesions with a sessile configuration and a diameter of 10 mm or more from the right colon (up to the splenic flexure) were classified as SSA/P; MVHP were obtained from the left colon and were < 5 mm in diameter. None of the polyps used in microarray gene profiling or RT-PCR contained pericryptal stromal spindle cells, had a conventional adenoma component, or had dysplasia. In addition to morphology, polyps were also characterized by BRAF and KRAS mutation analyses. No polyps that carried both the BRAF and KRAS mutations were identified. Informed consent was obtained from patients before the use of their samples, and the study was approved by the Royal Adelaide Ethics Committee (RAH Protocol No. 001201). DNA was prepared from polyp tissue macro-dissected from FFPE slides using the QIAamp DNA FFPE Tissue Kit (Qiagen, Valencia, CA).

The complete description of the effects of bracken fern has been

The complete description of the effects of bracken fern has been reviewed recently ( Gil da Costa et al., 2012a). Our previous studies showed that ptaquiloside is an immunosuppressor that caused a reduction in mouse splenic NK cell-mediated cytotoxicity and IFNγ production (Latorre et al., 2009). Moreover, we verified that selenium supplementation can prevent this reduction in NK-mediated cytotoxicity (Latorre et al., 2011). A greater incidence of chemical-induced preneoplasic

lesions are noted in mice immunosuppressed with bracken fern (Caniceiro et al., 2011), and our findings may be of great relevance in avoiding the increased susceptibility to cancer caused by the plant. The molecular mechanism underlying

ptaquiloside-induced Selleckchem NLG919 immunosuppression and its prevention by selenium are unknown. Thus, the objective of this study was to verify the mechanism of action of ptaquiloside-induced immunosuppression in splenic NK cells using gene expression microarray analysis. We performed transcriptome analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Fifty eight sixty-day-old CH5424802 research buy selleck screening library male C57BL/6J mice, bred in the Department of Pathology at the School of Veterinary Medicine and Animal Sciences, were used. The mice were housed in controlled temperature (22–25 °C), relative humidity (50–65%) and lighting (12 h/12 h

light/dark cycle) conditions. Drinking water and standard diet (Nuvilab-CR1®, Nuvital Nutrientes LTDA) were provided ad libitum. All procedures were performed following the Guide for the Care and Use of Laboratory Animals NIH publication No. 85-23 (http://www.nap.edu/readingroom/books/labrats/) and were reviewed and approved by the Bioethics Committee of the FMVZ-USP (process #1061/2007). Ptaquiloside was purified from dried P. aquilinum crosiers using a previously described procedure ( Oelrichs et al., 1995) that was later modified. In brief, ground plant material (100 g) was extracted using a Soxhlet apparatus with CHCl3 (48 h) followed by a 1:1 mixture of CHCl3/MeOH (48 h). The CHCl3/MeOH extract was evaporated to dryness at 40 °C under reduced pressure (rotary evaporation). The residue was collected in H2O (100 ml) and extracted twice with diethyl ether (100 ml) and then twice with n-butanol (100 ml). The n-butanol extract was concentrated under reduced pressure (rotary evaporator), and the residue was subjected to flash column chromatography [silica gel eluted using an EtOAc/MeOH gradient (0–12% MeOH)].

High-precision genome sequences and various molecular markers hav

High-precision genome sequences and various molecular markers have allowed mapping and identification of hundreds of QTLs

associated with grain traits in rice (http://www.gramene.org/). Many QTLs have been identified from different rice germplasms by a map-based cloning approach and these accomplishments imply the promise to help understand the molecular mechanisms underlying seed development and find ways to improve rice yield. GS3, a major QTL for grain weight and length with a minor role in grain width and thickness, was recently fine mapped to a genomic region of 7.9 kb on chromosome 3 using 5,740 BC3F2 plants [4]. GS3 find more encodes a putative transmembrane protein composed of four domains, and each functions differently in regulating grain size [5]. Sequence analyses showed that large grains are due to an early stop codon from a substitution in the second exon and, suggesting that GS3 functions as a negative regulator of grain size. Similarly, loss of GS3 leads to grain enlargement, which is true for GW2 [6], qSW5 [7] and TGW6 [8]. The major QTL for thousand-grain weight, TGW6, is mapped on chromosome 6 and encodes a novel

protein with indole-3-acetic acid (IAA)-glucose hydrolase activity. Deletion of 1-bp in TGW6 exon results in a premature stop codon to prevent the production of Cobimetinib cost the mature protein. It has been shown that function loss of the TGW6 allele results in simultaneous increase of grain weight

and yield [8]. Furthermore, GS5 is a recently cloned QTL, Resveratrol which variation is associated with grain size diversity in rice, thus may be useful in improving yield in rice and, potentially, other crops [9]. Its spatial expression patterns demonstrate that higher expression of GS5 results in larger grains, suggesting that GS5 is a positive regulator of grain size [9]. Another QTL affecting grain width and yield, GW8, encodes a protein to positively regulate grain size. The GW8 function on grain is attributable to a critical deletion polymorphism in the promoter region. In contrast, a loss-of-function mutation brings about a better quality of appearance [10]. In this study, we report the identification and fine mapping of GS2 candidate gene. Our results demonstrated that GS2 was a novel gene involved in the regulation of grain length and width in rice. The identification and functional characterization of GS2 will help breed high-yield rice varieties and understand the underlying molecular mechanisms to control grain shape in rice and other crops. Big-grain rice line CDL was crossed with a medium-grain line R1126. The resultant F1 plants were selfed to yield a F2 population of 1000 individuals, and the following recombined inbred lines (RIL). A differentiation of grain shape was observed in RIL28 line of F6, indicating heterozygous. The individual plants of RIL28 were selfed to generate a F7 population.

Das US-FNB wählte 18%, der EU-SCF 15% als durchschnittliche proze

Das US-FNB wählte 18%, der EU-SCF 15% als durchschnittliche prozentuale Resorptionsrate bei einer typischen westlichen Mischkost, die alle diese Einflussfaktoren in einer einzigen Zahl zusammenfasst. Um den durchschnittlichen Einfluss all dieser Faktoren auf die Bioverfügbarkeit zu ermitteln, wurde eine Reihe von Algorithmen entwickelt [75] and [97], und die Bioverfügbarkeit des Eisens wurde bei einer strikt vegetarischen Kost mit 5% und bei einer an Fleisch und Früchten reichen Mischkost

auf 15% angesetzt. Die von der FAO/WHO [75] abgeleiteten Empfehlungen zur Nährstoffaufnahme (RNI) müssen in verschiedenen Teilen der Welt auch bei erheblichen Unterschieden Vemurafenib mw hinsichtlich der Nahrungsmittelzubereitung anwendbar sein. Deshalb hat die FAO/WHO ihre RNIs auf der Basis von vier verschiedenen Annahmen zur Bioverfügbarkeit errechnet: 15%, 12%, 10% und 5% (siehe Tabelle 1). Da die Ernährung bei Säuglingen im Alter von 7 bis 12 Monaten nur wenig Fleisch enthält, aber reich an Getreide und Gemüse ist [98] wurde für diese Altersgruppe sowohl vom US-FNB [73] als auch von der FAO/WHO [75] eine Bioverfügbarkeit von 10% angenommen Bei Erwachsenen Männern

ist der basale Verlust BMS754807 an Eisen der einzige Faktor, der den durchschnittlichen Bedarf bestimmt. Das US-FNB rechnet mit einem Verlust von 14 μg Fe/kg pro Tag [99]. Dieser Wert wurde multipliziert mit einem durchschnittlichen Körpergewicht von 77,4 kg für die männliche Bevölkerung Ponatinib in den USA, entsprechend den Daten des National Health and Nutrition Examination Survey (= NHANES)

III, einschließlich der Standardabweichungen berechnet für alle Faktoren [73]. Bei den Berechnungen der FAO/WHO und des EU-SCF wurde eine Reihe verschiedener Körpergewichte angesetzt, um Altersunterschiede zu berücksichtigen. Für die USA wurde ein durchschnittlicher Bedarf von 1,08 mg Fe/Tag ermittelt, was einem Wert von 1,53 mg Fe/Tag für das 97,5. Perzentil entspricht, der die der täglich zu ersetzende Eisenmenge angibt. Bei einer angenommenen Bioverfügbarkeit für Eisen von 18% führt dies zu einem an Estimated Average Requirement (= EAR, geschätzter durchschnittlicher Bedarf) sowie einer RDA von 6 bzw. 8 mg Fe/Tag für erwachsene Männer ( Tabelle 1). Bei der Herleitung der FAO/WHO und des EU-SCF wird ebenfalls das 97,5. Perzentil eines EAR verwendet, und es ergibt sich ein Wert von 9,1 mg Fe/Tag, wenn eine durchschnittliche Bioverfügbarkeit von 15% angesetzt wird. Bei einer angenommenen Bioverfügbarkeit von 5% liegt die Empfehlung der FAO/WHO dreimal höher (27,4 mg Fe/Tag). Bei Frauen im gebärfähigen Alter müssen dass niedrigere durchschnittliche Körpergewicht und die Blutverluste während der Menstruation berücksichtigt werden.

, 1985, 1999) and may also develop in association with a variety

, 1985, 1999) and may also develop in association with a variety of focal brain lesions (Martin-Rodriguez and Leon-Carrion, 2010). Deficits of ToM in neurodegenerative disease have attracted much recent attention Etoposide molecular weight and on clinical and neuroanatomical grounds may be particularly relevant

to bvFTD (Schroeter, 2012; Poletti et al., 2012). Patients with bvFTD frequently have difficulty with aspects of social cognition that are likely to be relevant to ToM, including emotion recognition (Rosen et al., 2005; Kipps et al., 2009b; Omar et al., 2011), empathic concern and perspective taking (Lough et al., 2006; Rankin et al., 2006; Eslinger et al., 2011), and perception of humour and sarcasm (Snowden et al., 2003; Kosmidis et al., 2008; Kipps et al., 2009b). A specific mentalising deficit may be an early feature of bvFTD (Gregory et al., 2002; Adenzato et al., 2010) and neuroanatomical substrates for this deficit have been proposed. The distributed neural network that is damaged in bvFTD (Seeley et al., 2007, Zhou et al., 2010, Zhou et al., 2012 and Raj et al., 2012) overlaps brain areas previously implicated in ToM (Gallagher and Frith, 2003; Carrington and Bailey, 2009). Impaired ability to experience social emotions buy AT13387 has been linked to frontopolar damage in bvFTD (Moll et al., 2011). In addition, bvFTD is often associated with damage involving anterior temporal lobe regions

that represent social concepts underpinning normal mentalising (Zahn et al., 2009): these anterior temporal areas interact with medial PFC during moral

reasoning (Fumagalli and Priori, 2012), filipin while anterior temporal lobe damage has been implicated in the pathogenesis of cognitive and affective ToM deficits in another FTLD syndrome, semantic dementia (Duval et al., 2012). Relations between mentalising, ToM and music processing have not been widely studied; however, music is likely a priori to engage brain processes relevant to ToM and it is an attractive candidate stimulus for probing such processes in bvFTD. Music typically entails decoding of an emotional ‘message’ and music-making generally has a strong social context across human societies (Mithen, 2005; Levitin, 2007). Music has been shown to modulate semantic information in other cognitive systems, such as language (Koelsch et al., 2004). Deficits in processing emotion information in music have been demonstrated in various disease states, notably the frontotemporal dementias, and are dissociable from the processing of other kinds of musical perceptual information (Stewart et al., 2006; Omar et al., 2010, 2011; Johnson et al., 2011; Hsieh et al., 2012). The brain mechanisms of music processing in health and disease and the brain substrates for processing emotional information in music have received considerable attention (Blood et al., 1999; Blood and Zatorre, 2001; Griffiths et al., 2004; Gosselin et al., 2006; Koelsch et al.

Pdx1-Cre−mediated recombination appeared normal in fascin-deficie

Pdx1-Cre−mediated recombination appeared normal in fascin-deficient mice ( Supplementary Figure 4A), which showed a significant increase in survival ( Figure 2B). Fascin was expressed in KPC and absent from

FKPC tumors ( Figure 2C). Fascin null mice displayed similar end-point tumor histology and mass ( Figure 2D), with no significant difference in the number of undifferentiated or sarcomatoid lesions in the cohorts (not shown). KPC and FKPC GW3965 tumors showed identical proportions of cell proliferation and death ( Figure 2E and Supplementary Figure 4B). There was no detectable difference in recruitment of T cells (CD3), B cells (CD45R), macrophages (F4/80), or neutrophils (NIMP) between KPC and FKPC tumors ( Supplementary Figure 4C and D) or difference in platelet endothelial cell adhesion molecule staining of vascularization ( Supplementary Figure 4E and F). Together, these data suggest that cell proliferation, cell death, and fascin-deficient microenvironment do not contribute significantly to

prolonged survival of FKPC mice. We next examined mice at earlier time points during PDAC onset and progression. No differences were found at 6 weeks (Figure 2F), but PF-01367338 clinical trial by 10 weeks, 6 of 9 KPC vs 1 of 9 FKPC mice showed tumors ( Figure 2F). By 15 weeks, 9 of 10 KPC vs 3 of 6 FKPC mice showed tumors and FKPC showed smaller tumors ( Figure 2F). Loss of fascin significantly delays onset of PDAC and reduces early PDAC tumor burden, a surprising effect that has not been described previously. During the development of PDAC, ductal cells undergo EMT.10 Fascin is principally expressed in neural and mesenchymal derivatives during mammalian embryonic development,23 and 24 DOK2 suggesting that fascin could be a potential EMT target. EMT involves 3 families of transcription factors, the snail, ZEB, and bHLH families.7 and 25 We generated 10 independent KPC mouse PDAC cell lines that showed heterogeneous expression of E-cadherin, fascin, and EMT transcription factors (Tfs)

(Figure 3A), while normal primary ductal epithelial cells did not detectably express fascin or EMT Tfs ( Supplementary Figure 5A and B). Co-expression of E-cadherin and EMT Tfs indicate that most of our PDAC cell lines were in an intermediate stage of EMT ( Figure 3A, Supplementary Figure 5C). 10 Fascin-deficient PDAC cells also showed a similar heterogeneous expression of E-cadherin, fascin, and EMT Tfs ( Supplementary Figure 5D). Slug, zeb1, and zeb2 were expressed in all of our PDAC cell lines, while twist and snail were expressed in a subset ( Figure 3A). Levels of fascin and slug correlated most closely ( Figure 3A and B). Fascin and slug expression also correlated in a dataset of 23 human pancreatic cancer cell lines 22 ( Supplementary Figure 5E).

However, none of these studies used non-numerical tasks controlli

However, none of these studies used non-numerical tasks controlling for non-numerical

aspects of comparisons. Nevertheless, evidence demonstrates that both symbolic and non-symbolic comparison performance primarily reflects domain general comparison processes rather than properties of the number representation (Holloway and Ansari, 2008). Hence, the omission of a control task is a significant shortcoming and, in principle, studies without control tasks cannot draw any number-specific conclusions. In addition, the dot comparison task is inherently confounded by non-numerical parameters which cannot be controlled in each particular trial (Gebuis and Reynvoet, 2012 and Gebuis and Reynvoet, 2012; Szucs et al., 2013). Further, when tracking both numerical and non-numerical parameters in dot comparison tasks, event-related brain potentials (ERPs) only showed sensitivity to non-numerical parameters but not to numerical parameters (Gebuis and ABT-888 Reynvoet, 2012). Hence, in the dot comparison task participants’ supposedly numerical judgments can rely on non-numerical parameters in each particular trial. This problem also affects fMRI studies using non-symbolic magnitude comparison. It is noteworthy

that Landerl et al. (2004) is one of the most often cited studies in support of the MR theory. However, that study merely SB431542 ic50 demonstrated that DD have slower magnitude comparison speed than controls which can happen for many reasons. The distance effects did not differ in DD and controls and DD only showed a marginally steeper counting range RT curve than controls (pp. 117 and 119–120). In fact, the distance effect was not significant even in controls which suggests lack of power. In an extensive follow-up study Landerl and Kolle (2009) could not detect any robust basic number processing second difference between DD and controls and they concluded that they ‘did not find strong evidence that DD children

process numbers qualitatively differently from children with typical arithmetic development’ (ibid., abstract). While the MR theory of DD currently dominates neuroscience research, behavioral research identified several cognitive functions which play an important role in mathematical development and proposed several alternative theories of DD which have mostly been neglected by neuro-imaging research. First, a large volume of studies found deficient verbal and/or visuo-spatial WM function in DD (e.g., Hitch and McAuley, 1991, Passolunghi and Siegel, 2001, Passolunghi and Siegel, 2004, Keeler and Swanson, 2001 and Bull et al., 2008; Swanson, 2006; Geary, 2004) and longitudinal studies confirmed that WM function is related to mathematical performance (Geary, 2011, Swanson, 2011 and Passolunghi and Lanfranchi, 2012). WM serves as a limited capacity mental workspace for operands, operators, and retrieved numerical facts which have to be mobilized even during the simplest calculations (Geary, 1993 and Ashcraft, 1995).