, 1997). FGF-2 loss also resulted in a decrease in the slow-dividing stem cell pool and less neurogenesis (Zheng et al., 2004). EGFR is primarily expressed on type C cells and a limited number of type B1 cells, and studies of the EGFR-expressing population Selleck Sirolimus have indicated that most neurospheres arise from the C cell population (Vescovi et al., 1993 and Doetsch et al., 2002). Exogenous stimulation of the EGFR by ventricular infusion of EGF has striking effects within the adult VZ-SVZ. First, an increased number of type B1 cells contacting the ventricle are visible by electron microscopy (Doetsch et al., 2002). Second,

VZ-SVZ cells exhibit increased proliferation, and generate progeny that invade the surrounding parenchyma (Craig et al., 1996, Doetsch et al., 2002, Aguirre et al., 2005, Aguirre et al., 2007 and Gonzalez-Perez et al., 2009). Elevated EGF signaling biases VZ-SVZ cells toward the oligodendrocytic lineage—rather than giving rise to neurons, labeled EGF-stimulated Selleck SB203580 progenitors largely differentiate into oligodendrocytes or oligodendrocyte precursor cells (Gonzalez-Perez et al., 2009). The most likely endogenous ligand for this pathway is transforming growth factor-alpha (TGF-α). TGF-α-deficient mice exhibit decreased proliferation

within the adult VZ-SVZ, and these proliferation defects can be rescued in vitro by administration of EGF (Tropepe et al., 1997). More recently, TGF-α treatment has been suggested to decrease the percentage of highly motile neuroblasts within the RMS (Kim et al., 2009), but EGFR overexpression in NG2-positive progenitors has been reported to increase migration,

suggesting that this pathway may have different functions in distinct cell types (Aguirre et al., 2005). Intriguingly, the related receptor ErbB4 and its ligands, neuregulin 1 and 2, are also expressed in the adult VZ-SVZ and have been implicated in progenitor proliferation and the initiation of neuroblast migration (Ghashghaei et al., 2006). The platelet-derived growth factor (PDGF) signaling pathway also alters stem cell properties and already lineage decisions, although the endogenous source of ligand for this pathway is unknown. The PDGFRα is expressed by most GFAP-positive cells within the adult VZ-SVZ, and PDGF enhances in vitro neurosphere generation in cooperation with bFGF (Jackson et al., 2006). Infusion of PDGF, like EGF, induces elevated proliferation in VZ-SVZ cells, and many of these progenitors give rise to oligodendrocytes after ligand infusion has ended. However, PDGFRα staining and EGFR staining label separate populations of cells within the adult VZ-SVZ, suggesting that they affect stem and transit-amplifying populations respectively.

It is worth noting that so far there is little data in the developing

mammalian cortex concerning the relationship between spindle orientation and the cytoplasmic distribution of cell fate determinants in dividing cells. Future studies will be needed to show how the orientation of cell divisions relates to the distribution of cell fate determinants, and whether these factors are related to cell cycle length and cell fate choice. We anticipate that further work in this field will continue to shed light on the intricate mechanisms of neural progenitor cell division. “
“The inadequate access of young scientists to funding and university resources predates shrinking NIH budgets. In the late 1860s two young physicians, Fritsch and Hitzig, were associated with the Berlin Physiological Institute but did not have working space available there. They Alisertib ic50 went home, tied down their experimental animals on Fritsch’s wife’s dressing table, and performed perhaps the greatest neurophysiological experiment of all times. They analyzed the electric excitability GSI-IX manufacturer of cerebral cortex, first of an awake rabbit, then of awake dogs, and finally of anesthetized dogs. The scientists employed a primitive current generator and adjusted current strength by attaching the platinum stimulation electrodes to the tongue and choosing

currents that evoked tickling sensations. At some frontal stimulation sites they made an incredibly spooky observation. Currents evoked a wide variety of movements of the experimental animals, whereby the type of evoked movement varied with the cortical location of the stimulation site. Fritsch and Hitzig then went on and lesioned cortical sites representing forelimb movements. Such lesions resulted in a partial inability to do forelimb movements and greatly strengthened the conclusions

of the stimulation experiments. The investigators correctly concluded that motor functions were localized at discrete sites in the cerebral cortex. The results shook the world. Cortical function could be studied scientifically. MYO10 The neurophysiologist’s electrodes replaced the phrenologist’s fantasies. The Scottish physiologist Ferrier reproduced Fritsch and Hitzig’s results in monkeys. By 1875—just five years after the initial publication—it was clear that neural activity in motor cortices is both necessary and sufficient for motor control. Even though Frisch and Hitzig’s experiment was immensely illuminating and once and for all clarified our thinking about the brain, their motor mapping approach also elucidated a complexity of cortical organization that we are still struggling with today. When more and more motor maps from different investigators and different species became available it became clear—much to the surprise of early investigators—that motor maps differed between species and that there is not one universal mammalian cortical motor organization.

This suggests a strong feature Trametinib tolerance in this area, which generalizes even beyond sensory input modality and early sensory experience, while maintaining the relative category selectivity implied by the term “visual word form area.” Moreover, this area shows remarkable adult plasticity, such that it can be recruited in an adult blind individual reading in a novel sensory modality after as little as 2 hr of training (Figure 4). After ∼70 hr of training in a group of subjects,

this area already displayed full category selectivity (Figure 2). These findings impact several of the major issues regarding the function and developmental origin of the VWFA, as well as the balance between plasticity and conserved cortical functions resulting from sensory deprivation. Specifically, they suggest that the VWFA performs a highly Bosutinib flexible task-specific reading-related operation that can be sensory modality independent (Reich

et al., 2012). We suggest that this operation is the learned link between letter shapes and their associated phonological content. This category and task selectivity is maintained in the congenital absence of vision, despite otherwise extreme plasticity for other functions and input types shown previously in the blind brain (see reviews in Frasnelli et al., 2011; Merabet and Pascual-Leone, 2010; Striem-Amit et al., 2011). This implies the presence of innately determined constraints (Striem-Amit et al., 2012a) on the emergence of VWFA selectivity for reading. Furthermore, in the context of visual rehabilitation, this study also shows that the recognition of many complex visual stimulus categories can be learned using SSDs, including detailed images of faces and houses (see Movies S1 and S2). We describe how such training was implemented on computer and in natural three-dimensional (3D) environments, details

of which may be of interest to those specializing in visual rehabilitation (see Supplemental Experimental Procedures). In the next sections, we address all these topics in more depth. In the visual modality, the VWFA has proved to be selective for letters over other complex visual stimuli such as drawings of objects, faces, until and houses (Cohen and Dehaene, 2004; Dehaene and Cohen, 2011; Dehaene et al., 2010; Hasson et al., 2002; Puce et al., 1996; Szwed et al., 2011; Tsapkini and Rapp, 2010), thus justifying its “visual word form area” label. Note that the VWFA, like other specialized ventral areas (Kanwisher, 2010), is also partially responsive to stimuli from nonpreferred categories and that its preference for alphabetic stimuli may be missed under some experimental conditions (reviewed in Price, 2012; Price and Devlin, 2011).

Of the effector caspases only Drice and Dcp-1 have been shown to be enriched in

the larval nervous system, whereas Dronc and Dredd are initiator caspases with enriched expression in the larval CNS ( Chintapalli et al., 2007). We first tested whether caspase overexpression might cause motoneuron degeneration. Overexpression of the initiator caspase Dredd in motoneurons was without effect. However, overexpression of Dronc in motoneurons caused embryonic lethality, suggesting that Dronc might be an initiator caspase in motoneurons. We then decreased GAL4-dependent UAS-Dronc expression by lowering the temperature learn more at which we raised the animals to 18°C. Under this condition, rare larvae survive to late larval stages ( Figure 6F). These animals show severe NMJ degeneration with many complete NMJ eliminations. These data demonstrate that

Dronc expression is sufficient to cause NMJ degeneration. Consistent with this finding, we demonstrate that Flag-tagged Dronc ( Yang find more et al., 2010) traffics to the axon and presynaptic nerve terminal ( Figure 7A). We next overexpressed effector caspases. Drice was without effect. By contrast, overexpression of UAS-Dcp-1 in motoneurons caused severe motoneuron degeneration ( Figure 6). We confirmed the severity of anatomical NMJ degeneration by recording from these NMJs. We demonstrate that synaptic transmission is severely disrupted ( Figure S8). Next, we coexpressed UAS-Dcp-1 and UAS-CD8-GFP in a small subset of motor axons using the Eve-GAL4 driver so that we could visualize individual

axons in the peripheral motor nerve. We label between one and four motor axons with UAS-CD8-GFP using the Eve-GAL4 driver. Overexpression of UAS-CD8-GFP alone labels individual motor axons that can be traced continuously, without break, from the CNS to the NMJ ( Figure 6C). By contrast, when UAS-CD8-GFP is coexpressed with UAS-Dcp-1, we find clear evidence that axons have a narrower caliber and clear evidence of axonal breaks or fragmentation ( Figure 6D). These data demonstrate that expression of UAS-Dcp-1 causes axonal degeneration as well as degeneration at the nerve terminal. As a control, we demonstrate that found the glial expression of UAS-Dcp-1 is without effect ( Figure 6E). As with the initiator caspase Dronc, Venus-tagged Dcp-1 traffics to the axon and presynaptic nerve terminal ( Figure 7B). The observation that overexpression of UAS-Dcp-1 is able to initiate caspase activity suggests that this caspase can be autoactivated through overexpression because it seems unlikely that there is a constitutively active initiator caspase activity in motoneurons. This is consistent with prior demonstration that caspase 6, unlike caspase 3 and 7, can undergo autoactivation ( Klaiman et al., 2009 and Wang et al., 2010).

Because NeuroD1 mis-expression by itself does not affect cell migration ( Mattar et al., 2008), we hypothesized that the loss of Unc5D may be responsible for the delayed migration. We repeated the FoxG1 gain-of-function and rescued Unc5D expression specifically at the postmitotic multipolar phase ( Figure 3F) by using a NeuroD1 promoter construct ( Figures S1H and S1I). Remarkably, restoration of Unc5D expression in NeuroD1-positive cells partially Selleck SB203580 rescued the migration phenotype in that there was a dramatic increase in cells that entered the cortical

plate after 3 days ( Figure 3F) compared to the ones that solely experienced FoxG1 gain-of-function ( Figure 3E). We further examined whether Unc5D restoration in FoxG1 gain-of-function cells could also correct their altered

laminar identity ( Figure 2 Ruxolitinib concentration and Figures S3E–S3H). Indeed, when Unc5D expression was restored in FoxG1 gain-of-function cells at the multipolar phase, we observed that by P7 a substantial number of them were now appropriately located in layer IV ( Figure 3G) and possessed the correct molecular profile for this layer ( Figures 3G′, 3H, and 3I, Cux1-on, Brn2-low, and RORβ-on, see also Figure 3J). How could Unc5D play such a critical role in regulating the early to late transitions within the multipolar cell phase? It has been shown that Unc5D is a receptor involved in Netrin-signaling in the postnatal cortex ( Takemoto et al., 2011) and, in the context of axonal guidance, alters the response of Dcc (Deleted in colorectal carcinoma) to Netrins in growth cone turning assays ( Hong et al., 1999). We found that both Dcc and Unc5D are expressed within the intermediate zone ( Figures S4A and S4B) and, in fact, are the only known Netrin receptor molecules expressed in this region (Unc5A,

5B, 5C, Neogenin, and Dscam are not expressed within the intermediate zone, see Figures S4C–S4H). However, unlike the downregulation of Unc5D we have observed in FoxG1 gain-of-function cells ( Figure 3D), Dcc expression for was not affected (data not shown). This suggests that, similar to what has been demonstrated in the context of axon guidance, disruption of the Unc5D/Dcc balance by loss of Unc5D might be responsible for the delay in migration. We directly tested this idea and found that Dcc overexpression delays cell migration at the intermediate zone ( Figure 3K), in a manner similar to FoxG1 gain-of-function, and this can be rescued by simultaneously increasing the levels of Unc5D ( Figure 3L).

25, p = 0.036), and the transverse temporal region (t[21] = 2.79, p = 0.011). Accumbens favored win information, showing significant win-tie decoding (55% accuracy, on average, t[21] = 3.77, p < 0.001) but not tie-loss (51% average accuracy, t[21] = 1.17, p = 0.13). Caudal ACC also favored win-tie over tie-loss discriminations (56% versus 52% accuracy), but still showed a significant (p < 0.05, uncorrected) tendency to decode tie-loss (t[21] = 1.74, p = 0.048). Transverse temporal region showed an ability to decode tie versus loss

information (t[21] = 3.21, p = 0.002) but not win versus tie (t[21] = −0.28, p = 0.6). In a similar searchlight analysis, we contrasted the ability of each voxel to decode wins-ties and ties-losses. We found eight small clusters that differed significantly in their Selumetinib cost ability to perform these two classifications (Table S6; figures not shown because these small clusters did not show up well when projected to the surface). Regions that did better on win-tie than tie-loss (p < 0.001, k = 10) were in the right basal ganglia (medial globus pallidus), VE-821 chemical structure the left ACC, and left middle frontal gyrus. Regions performing better

on ties-losses were the left amygdala and regions in the right IPL, left medial temporal, left fusiform and left middle temporal gyrus. In total, clusters showing these differences only encompassed 136 voxels, far fewer than those with significant three-way win-tie-loss classification (equal to only 0.4% of the number of voxels able to decode win-tie-loss). Of 34,520 above-chance voxels in three-way win-tie-loss classification, only 25 voxels showed a significant difference between win-tie and tie-loss classification

(42 without cluster correction). Therefore, signals related to both reinforcements and punishments were remarkably ubiquitous, and there was very little difference between encoding of the two. The addition of tie outcomes in Experiment 2 afforded the ability to distinguish signals related to reinforcement and punishment from those related to salience. One possible explanation for the ubiquitous reward signals in Experiment 1 is that one of the two outcomes first in the matching pennies game is more attention-demanding or salient (Maunsell, 2004, Bromberg-Martin et al., 2010, Chun et al., 2011 and Litt et al., 2011). By contrast, during rock-paper-scissors, the “tie” outcome should be less salient and arousing than both wins and losses. We evaluated the salience hypothesis by using a pair of classifiers. First, we trained classifiers to discriminate wins from ties (win-tie classifier), then evaluated whether they tended to classify unseen losses as wins or ties. Next, we also trained classifiers to discriminate ties from losses (tie-loss classifier), then evaluated whether they tended to classify unseen win trials as ties or losses.

Sensory input is critical for object localization and recognition, and also to guide future movements of the whiskers. By collating our studies of long-range connections with previous data on thalamocortical (Bureau et al., 2006, Lu and Lin, 1993, Meyer et al., 2010b and Petreanu et al., 2009) and local cortical circuits (Hooks et al., 2011, Lefort et al., 2009 and Svoboda et al., 2010) it is possible to sketch out a circuit diagram for the cortical vibrissal sensorimotor loop in mice (Figure 8). Forces acting on whiskers excite sensory neurons in the trigeminal ganglion, triggering activity which ascends through the brainstem into VPM and L4 neurons in the barrel cortex (Petersen, 2007 and Svoboda

et al., 2010). L4 stellate selleck chemicals llc cells mainly excite L2/3 neurons, which in turn excite ABT-888 neurons in L5A and also in L5B (Armstrong-James and Fox, 1987, Brecht et al., 2003, Brecht and Sakmann, 2002, Hooks et al., 2011, Lefort et al., 2009 and Manns et al., 2004). A subset of L2/3 and L5A neurons project to vM1 (Figures S5A, S5B, and S9C), where they strongly target upper layer neurons in L2/3 and L5A, and only weakly deep layer neurons in L5B and L6 (Figures 4C–4F,

6, and S6). Upper layer neurons in vM1 receiving strong input from vS1 project back to vS1 (Figures 2B, 2C and 7B), where they synapse onto neurons in L2/3, L5A, and L5B (Petreanu et al., 2009). Cortico-cortical neurons in L2/3 and L5A in vM1 are thus the nexus of a powerful disynaptic feedback loop (vS1, L2/3/5A ←→ vM1, L2/3/5A), linking sensory and motor cortex (Figure 8). This until loop apparently violates the no-strong-loops principle which is thought to govern inter-areal connectivity in the visual system (Crick and Koch, 1998). Since AAV infected both L2/3 and L5A cells in vS1 (Figure S1A), additional experiments are required to determine the separate contributions of L2/3 and L5A neurons to activating targets in vM1 (Aronoff

et al., 2010). A small subset of deep L6 cells in vS1 also projected to vM1 (Figures S5A, S5B, and S9C). These neurons were only sparsely infected by the AAV virus, and their contribution to the vS1 → vM1 projection, although likely small in total, was underrepresented in our study. How does this superficial feedback loop communicate with the deep layer output neurons in vM1? The local circuit in somatic (Weiler et al., 2008) and vibrissal (Hooks et al., 2011) motor cortex shows a top-to-bottom organization. Interlaminar excitation is strongest from superficial layers downward, with a powerful descending projection from L2/3 to the border of L5A and L5B (Hooks et al., 2011). Weaker projections exist from L5A to L5B. Similarly, L2/3 and/or L5A neurons in vM1 excite L5B neurons in vS1 (Petreanu et al., 2009). L5B neurons in vM1 (Figures 2 and S5D) and vS1 (Matyas et al., 2010) are projecting to motor centers in the brainstem.

, 2001). EC did not prevent filopodial sprouting. Instead it resulted in a specific reduction of spine density on the caliber 3 dendrites normally dominated by VC after EO (Figures 5B and 5C). Spines and filopodia on caliber 4 dendrites were unaffected (n = 25, p > 0.50). These results suggest a two-step process driving dendritic development at EO: a pattern vision independent induction of filopodia and a pattern-vision dependent spine retention on VC-recipient dendrites. The changes described above suggest a particular role for EO in sprouting and synapse formation by VC afferents.

To examine this, we labeled small numbers of corticocollicular axons in rat pups (their larger size compared to mice making specific labeling of a smaller subset of cortical ZD1839 neurons possible). Single strands of DiI-saturated Gelfoam

were inserted in the monocular, medial region of ipsilateral VC (Figure 5D), a region that projects to posterior-dorsal sSC and responds to the same visual field locale as retinocollicular axons terminating in that region (Khachab and Bruce, 1999). Maximal DiI spread from the center of these topographic injections extended on average 9.2% of the anterior-posterior (A-P) axis of the cortex, and never >12.5%. Reconstructions of corticocollicular Anticancer Compound Library solubility dmso axons illustrate that at P12-P13, just before EO in rat, individual corticocollicular axon terminals extend ectopic side branches along their anterior-posterior (A-P) length before terminating in the posterior third of the sSC, where some tended to be more highly branched (BEO; Figure 5E). The collateral branching pattern was reminiscent of the early retinocollicular projection (Simon and O’Leary, 1992). By P15-P16, however, 2–3 days

AEO on P13, ectopic side branches were reduced, whereas the terminal zone (TZ) arbor became densely branched. To examine the pattern-vision dependence of the VC axonal sprouting/refinement, eyelids of littermates of the same animals were sutured of closed on P13, before EO. Two to three days of eye closure resulted in a dramatic change in corticocollicular terminals. The TZ normally seen after EO was not present, and only infrequent short collateral branches remained along the VC axon (EC; Figure 5E). This suggests robust pruning of VC synapses occurred in the visually deprived condition. To quantify these EO dependent changes, 160 mm3 volumes of tissue were sampled at regular intervals along the A-P length of the sSC. The complexity of the VC arbors within these volumes was measured by counting branch points and end points on each segment of all cortically labeled axons. After EO, axons in the posterior fifth of the sSC had significantly more branch points and endpoints compared to the anterior sSC (Figure 5F).

0011), thus indicating a predominance of IL-4 compared to IFN-γ in the infected animals. The IFN-γ/IL-10 ratio was 13 times higher in the control group compared to the IFN-γ/IL-10 ratio in the infected group, indicating a predominance of IFN-γ over IL- 10 in control animals, and this difference was statistically significant (p = 0.0075). Because both IL-4 and IL-10 expression are increased in the livers of infected animals, we

performed a correlation test between these cytokines. We found an r2 = 0.8394 (p = 0.0102) indicating that there is a positive linear relationship between the increased expression of both cytokines in the liver of infected animals ( Fig. 3). Furthermore, the two animals without fibrosis, necrosis, hyperplasia and calcification of the ducts had the lowest values of IL-4 and IL-10 expression. It is well established that the activation of T cells, which determines the ISRIB cytokine profile, is a critical event that is able BTK inhibitor solubility dmso to direct the outcome of infections (Maizels et al., 2004 and Anthony et al., 2007). It has been shown that many helminth infections are typically characterized by TH2 lymphocyte responses (Finkelman et al., 1991). During the course of its evolution, F. hepatica has created interactions that allow its survival and persistence in the host. To ensure the survival of both the parasite and the

host, the interactions of the parasite with the vertebrate host require immunomodulatory mechanisms capable of interfering with the host immune and inflammatory responses that occur during infection. Among the various strategies adopted by the parasite that allow its development in the vertebrate host, the modulation of the TH2 cell response is related to the production of cytokines responsible for the pathophysiology of infection ( Rojo-Vázquez Linifanib (ABT-869) et al., 2012). The role of cytokines in the natural infection of cattle in the chronic phase of fascioliasis highlights the importance of the cellular response and demonstrates that humoral mechanisms alone

are not sufficient to promote the protection of the host. The involvement of the cytokines IFN-γ, IL-4 and IL-10 evaluated in the present study using qRT-PCR, which has high specificity and sensitivity, enabled a comparative analysis of the expression of these genes in the liver tissue of naturally infected cattle during the chronic phase of fascioliasis. We found suppression of IFN-γ expression in infected animals. Other authors have reported similar results in peripheral blood during acute and chronic phases of fascioliasis in naturally and experimentally infected cattle (Clery et al., 1996, Clery and Mulcahy, 1998, Waldvogel et al., 2004, Flynn et al., 2007, Ingale et al., 2008 and Flynn and Mulcahy, 2008). Like these authors, we suggest that the levels of IFN-γ present in the host response during the first weeks after infection result in a negative modulation during the chronic stage.

Second, we investigated whether PG14 PrP induced an abnormal calcium response in wild-type neurons. CGNs from C57BL/6J mice were transfected with a bigenic plasmid that drives efficient PrP and EGFP expression

in CGNs (Drisaldi et al., 2004), EGFR inhibitor and the depolarization-induced calcium rise was measured in EGFP-positive cells. PG14 PrP-transfected cells had a significantly smaller rise in calcium than untransfected or wild-type PrP-transfected neurons (Figure 4B), indicating that acute PG14 PrP expression was sufficient to impair VGCC function. The biosynthetic maturation of misfolded PG14 PrP molecules in the ER is delayed, and they accumulate in the neuronal secretory pathway (Drisaldi et al., 2003 and Fioriti et al., 2005). To assess whether intracellular PG14 PrP retention plays a role in the VGCC defect, we analyzed the depolarization-induced calcium rise in CGNs transfected with a version of PG14 PrP with

a deletion of amino acids 114–121 in the hydrophobic core (PG14/ΔHC). This molecule is less prone to misfolding and delivered to the cell surface more efficiently than its full-length counterpart (Biasini et al., 2010). CGNs from C57BL/6 mice were transfected with PG14/ΔHC PrP, or with a version of PrP carrying the hydrophobic core deletion but not the PG14 mutation (ΔHC). The calcium responses of PG14/ΔHC PrP-expressing cells were comparable to those of the wild-type and Birinapant chemical structure ΔHC controls (Figure 4B), suggesting that misfolding and intracellular retention of mutant PrP were necessary to induce the defect in calcium influx. Reduced intracellular calcium influx and current amplitude in PG14 CGNs might be due to changes in VGCC expression,

biophysical properties, or membrane targeting. VGCCs are heteromeric proteins consisting of the pore-forming CaVα1 subunit, which governs the biophysical and pharmacological properties of the channel, and the auxiliary α2δ and CaVβ subunits, which regulate the cellular trafficking and activity of CaVα1 (Dolphin, 2009). Glutamate release from CGNs is mainly governed by P/Q-type channels made of the CaVα1A, α2δ-1, and CaVβ4 subunit isoforms (Mintz et al., 1995). To test whether expression of these channels was altered in Tg(PG14) mice, we measured enough CaVα1A and α2δ-1 levels in cerebellar postnuclear supernatants and cultured CGNs. There were no differences in these proteins between Tg(PG14) and Tg(WT) mice (data not shown; Figure S7B), indicating that the calcium defect in the mutant mice was not due to altered VGCC expression. Because our data pointed to a role of intracellular PG14 PrP retention, we hypothesized that mutant PrP interacted with VGCCs in transport organelles, interfering with their trafficking toward the plasma membrane. Of the different channel subunits, α2δ-1 was the best candidate for an interaction with PrP because PrP is a glycosylphosphatidylinositol (GPI)-anchored sialoglycoprotein (Stahl et al.