Interestingly, not every burst in the preBötC is transmitted to t

Interestingly, not every burst in the preBötC is transmitted to the XII and in some slice preparations the XII can fail to burst in phase with the respiratory cycle generated within the preBötC (Fig. 1; Ramirez et al., 1996). It is conceivable that such an activation failure could provide a mechanistic explanation for XII inactivity during continued inspiratory respiratory rhythm generation from the preBötC. The inspiratory rhythm

generated in the preBötC would then continue to be transmitted to the phrenic nucleus (Fig. 1). Continued activation of the diaphragm is an important aspect of OSA, as it is the activated diaphragm that produces the expansion of the thorax which together with a lack of genioglossus http://www.selleckchem.com/products/gsk1120212-jtp-74057.html activation creates negative pressure and pharyngeal collapse. At this point, we do not know how the respiratory drive from the preBötC is transmitted under conditions that mimic sleep states or conditions that mimic sleep apnea. During hypoxia, however, transmission failure from the preBötC to the XII motoneurons is increased (Pena et al., 2008). Thus, an important avenue for future research will be to understand how chronic intermittent hypoxia or certain neuromodulatory conditions associated with sleep can

cause such transmission failures between the respiratory rhythm generator and the XII motor output. Investigating this issue could provide important and selleck screening library much needed clues into the pathology of OSA. In addition to the onset and maintenance of airway occlusion, recovery from an airway obstruction has been the subject of intense discussions (Fig. 2). One notion is that reflex recruitment of pharyngeal dilator muscles is insufficient to open the airway once it is occluded and that arousal is required for the termination.

This is an important consideration, since breathing instabilities that promote OSA likely involve pathological changes in arousal threshold (Younes, 2004). Arousal is stimulated by increased negative pharyngeal pressure and increasingly hypoxic and hypercapnic conditions that in turn increase respiratory drive (Berry and Gleeson, 1997, Gleeson et al., 1990 and Kimoff et al., 1994). The stimulation of arousal then activates dilator activity and opens the airways (Remmers et al., 1978). Avelestat (AZD9668) Yet, arousal is not required for apnea termination (Younes et al., 2012). Fig. 2 illustrates the recovery from an airway occlusion which is typically abrupt and associated with a sudden burst of genioglossus EMG (Berry and Gleeson, 1997, Rees et al., 1995, Remmers et al., 1978, Wulbrand et al., 1998 and Wulbrand et al., 2008). The abrupt increase in genioglossus muscle activity seems to be due to the recruitment of phasic inspiratory motor units (Wilkinson et al., 2010). Wulbrand and co-workers proposed that this burst is synchronized with the generation of sigh or sigh-like neuronal mechanisms (Wulbrand et al., 1998). The induction of sighs by airway occlusion has also been reported by Alvarez et al. (1993).

Our results also

showed that REKRG not only stimulates eN

Our results also

showed that REKRG not only stimulates eNOS phosphorylation and NO production but also decreases VCAM-1 and COX-2 expression. These findings suggest an important role for Rg3-enriched ginseng extract in vascular protection. In conclusion, this study showed that the stimulatory effect of REKRG administration on vascular endothelial NO production through phosphorylation of eNOS is likely to have relevance for not only inhibition of VCAM-1 and COX-2 expression but also decreased aortic intima-media thickness, which improves cardiovascular function and prevents atherosclerosis. Apoptosis inhibitor All authors declare no conflicts of interest. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the

Korean Government (MEST; no. 2011-0023858). The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/certificate/H2CZjI. “
“Unlike other ginsenosides with various pharmacological activities (e.g., ginsenoside Rg3) [1] and [2], ginsenoside Rp1 (G-Rp1) is a ginseng saponin Z-VAD-FMK datasheet artificially prepared from crude ginsenosides (e.g., G-Rg5 and G-Rk1) obtained from Panax ginseng Meyer by reduction and hydrogenation [3]. The phytochemical features of G-Rp1 include its chemical stability, and various pharmacological approaches have suggested its value as a biologically

active ginsenoside. It has been reported that G-Rp1 is able to prevent skin papillomagenesis induced by 7,12-dimehtylbenz(a) anthracene [4], suppress the proliferation and metastatic processes of cancer cells [5], and reverse multidrug resistance in tumor cells [6]. In addition, G-Rp1 has also been found to block interleukin-1 production and diminish platelet activation and thrombus formation [7] and [8]. It has also been revealed that G-Rp1 blocks pathways linked to multidrug resistance gene-1 (MRD-1), Src, Akt, and I-kappaB kinase (IKK) in apoptotic and inflammatory processes [6], [9] and [10]. Although these experiments have explored the potential mechanisms underlying the Beta adrenergic receptor kinase anticancer and anti-inflammatory activities of G-Rp1, the proteins responsible for these pharmacological actions remain unclear. Therefore, in this study, we used proteomic analysis to investigate the effect of G-Rp1 on the protein profiles and expression levels in several cancer cells to understand the mechanisms underlying its anticancer activity. G-Rp1 (Fig. 1) of 97% purity dissolved in 100% dimethylsulfoxide was prepared using established protocols [3]. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) were purchased from Sigma–Aldrich (St. Louis, MO, USA). Polyvinylidenedifluoride membrane was purchased from Bio-Rad Laboratories, Inc. (Hercules, CA, USA).

In the Orinoco, abundant carbonized maize was recovered from habi

In the Orinoco, abundant carbonized maize was recovered from habitation sites and human bone stable carbon isotopes indicate high consumption levels (Roosevelt, 1997:196–209; Merwe et al., 1981). In Bolivia, a wide range of crops has been tentatively identified

at living sites, but maize is the most widespread, also (Dikau et al., 2012). In the future, human bones from the cemeteries in the Bolivian and Guianas sites can also be analyzed to establish the level of maize consumption. The wetland human works remain today as obvious topographic and vegetation anomalies in their habitats. Such major topographic and soil quality alterations are likely to have had an impact on the regional ecosystem. Raising fields and growing herbaceous crops on them would have reduced open water, waterlogging, and the shade from the natural vegetation cover, raising KRX-0401 mw temperatures. Floodplain forests, though less diverse than upland forests, represent a significant percentage of the biological diversity of Amazonia (Erickson, 2010, Junk et al., 2010, Salo et al., 1986, Pires, 1984, Roosevelt, 1991a and Roosevelt, 1999b), so overall diversity could have selleckchem diminished by their removal, despite the addition of cultigens and orchard trees. Such changes might have had effects on regional or even hemispheric scale, because

vegetation cover, surface moisture, and thermal patterns greatly affect patterns and amount of rainfall (Harper et al., 2010, Nepstad et al., 1994 and Salati and Vose, 1986). They also would have limited the space for seasonally migrating waterfowl. Outstanding

among terra firme earthwork complexes is the prehistoric system discovered in the Kuikuru reserve area of the Upper Xingu, a southern tributary of the Amazon. This is an interfluvial region that nonetheless possesses localized stretches of riverine alluvium. First noted in the mid-20th century by ethnographers Dole and Carneiro, the complex became the focus of a project of archeological excavation Ibrutinib purchase and mapping (Heckenberger, 2004 and Heckenberger et al., 1999). Settlements took the distinctive shape of this region’s current ethnographic round villages, in which long-houses are arranged in a circle around a large plaza containing a roofed ceremonial activity area. The ethnographic site circles have important cosmological and social symbolism relating mythic events to modern social groups in prescribed ceremonial relationships. The ancient villages, though similar in form, were much larger and more numerous, and each was furnished with a series of earth structures. Around the settlements were raised earth rings and ditches, possibly with defensive functions, indicating that the population density occasioned conflict in the region. These villages, 20 in number, were connected by wide, high earth roads, indicating that they were all part of a coherent socio-political and ceremonial system that covered 400 km2. There is a site size hierarchy, from ca.

For nearly two millennia, it was a symptom and symbol of China’s

For nearly two millennia, it was a symptom and symbol of China’s never-ending problems with “frontier barbarians” who worked continuously to harvest some of the nation’s wealth for themselves (Barfield, 1989). It survives very visibly to the present, albeit now in greatly dilapidated condition except for a few limited restorations. The new Qin emperor also created for his personal afterlife a huge mounded tomb almost half a square km in extent, still unexcavated but, according to recorded legend, containing

a detailed replica of the royal palace surrounded by rivers of mercury. Well-digging in 1974 led to the discovery, about two km away from this location, of a fully equipped “spirit army” buried in two large pits that selleck screening library included perhaps 3000 life-sized this website “terracotta warriors” and associated pottery models of horses, chariots, and weaponry. Excavations quickly captured world attention and the work continues, now sheltered and displayed beneath a vast metal hangar that could house a considerable fleet of the world’s largest jet airplanes (Fig. 2). The Zheng Guor Canal system, according to historical records created in 246 BC by the pre-imperial Qin State, was laid out over a course of some 200 km and linked two local rivers. It hugely expanded the agricultural output of the Qin region and helped afford its lord the economic wherewithal to gain

greater control STK38 over his rivals. Beyond the constructions subsequently ordered by Emperor Qin Shihuangdi there were also infrastructural projects sponsored by other wealthy “houses” of the region that we still see attested archeologically – dams, canals, vast irrigated agricultural fields, and roads – that are not as well preserved as the displays of royal wealth we see in the Qin emperor’s funereal Terracotta Army. Nevertheless,

these modifications are evident on the landscape and referred to in written records of the time. A third-century historical source quoted by Elvin (1993) vividly portrays the busy cultural landscape of the Qin and following Han periods: “The households of the powerful are [compounds] where one finds hundreds of ridge beams linked together. Their fertile fields fill the countryside. Their slaves throng in thousands, and their [military] retainers can be counted in tens of thousands. Their boats, carts, and their merchants spread out in every direction…. The valleys between the hills cannot contain their horses, cattle, sheep, and swine. The great array of huge mounded earth tombs inside the boundaries of modern Xi’an, created by the Han emperors who followed Qin Shihuangdi, further attests the Imperial capacity of the time for enormously labor-intensive construction projects that created large areas of anthropogenic landscape in the Wei River Valley. Each Han tomb was an artificial mountain that took armies of men and animals years to build.

However, land area data do not tell the whole story, as subaqueou

However, land area data do not tell the whole story, as subaqueous aggradation must precede land emergence. LP6 has been an area of significant deposition throughout the history of river management on the UMRS (Fig. 6). Between 1895 and 2008, an average of 2.2 m of sediment aggraded in the subset of LP6 for which bathymetric data were analyzed (Table 4). For the 0.34 km2 area, sediment storage increased by ∼750,000 m3. Some areas increased in elevation by up to 6.6 m, while other areas deepened by up to 6.3 m. The greatest aggradation has been in areas this website that have emerged since the 1990s. In particular, the lower portion of lower Mobile Island was the deepest

part of the area in 1895. The river’s right bank and immediately south of the Island 81 complex have scoured most deeply. Degradation of the river

bottom upstream of the present position of upper Mobile Island has also occurred. Between 1895 and 1931, the aggradation rate was 21 mm/yr, resulting in 0.7 m of sediment accumulation. Elevation changes ranged from +3.7 m to −4.0 m during this period, with the greatest accumulations occurring where land emerged attached to Island 81, upstream of upper Mobile Island, and in the area that is now the downstream portion of lower Mobile Island. Areas of degradation mostly corresponded to areas of emergent land in both 1895 and 1931, and are likely the result of uncertainty in assigning land elevations that lacked survey data. The overall estimate of aggradation in this period is likely to be underestimated, since it is unlikely that land elevations were decreasing. Between 1931 selleck chemical and 1972, Rebamipide the aggradation rate was 24 mm/yr, resulting in 1.0 m of accumulation. While 5 years of the period occurred before Lock and Dam #6 closure, it is clear that substantial aggradation occurred following closure, and the rate is attributed to post-dam conditions. Aggradation occurred over large swaths of the bathymetric study area, with elevation changes ranging from +3.5 m to −2.4 m. The greatest aggradation occurred at lower Mobile

Island, which emerged above water near the end of the period. Substantial aggradation also occurred at upper Mobile Island, which expanded substantially between 1940 and 1972. Elevation decreases occurred along the right riverbank and upstream of upper Mobile Island. Some decreases may also be attributed to uncertainty in assignment of land elevations in the 1931 dataset, but all occurred where land disappeared and has not reemerged following closure of Lock and Dam #6. Between 1972 and 2008, the aggradation rate was 14 mm/yr, resulting in 0.5 m of sediment accumulation. Thus, sedimentation rate was ∼40% lower in this period than 1931 to 1972 and ∼30% lower than between 1895 and 1931. Similar to earlier periods, elevation changes ranged from +3.2 m to −4.

In addition to problems associated with the high radioactive cont

In addition to problems associated with the high radioactive contamination which justifies its urgent monitoring at the regional scale, this event, although regrettable, also constitutes a unique scientific opportunity to track in an original way particle-borne transfers that play a major role Docetaxel in global biogeochemical cycles (Van Oost et al., 2007) and in the transfer of contaminants within the natural environment

(Meybeck, 2003). Conducting this type of study is particularly worthwhile in Japanese mountainous river systems exposed to both summer typhoons and spring snowmelt, where we can expect that those transfers are rapid, massive and episodic (Mouri et al., 2011). During this study, fieldwork required being continuously adapted to the evolution of the delineation of restricted areas around FDNPP, and laboratory experiments on Fukushima samples necessitated the compliance with specific radioprotection rules (i.e., procedures for sample

preparation, analysis and storage). In addition, the earthquake and the subsequent tsunami led to the destruction of river gauging stations in the coastal plains, and background data (discharge and suspended sediment concentrations) were unavailable during the study period. Monitoring stations have only become operational again from December 2012 onwards. In this post-accidental context, this paper aims to provide alternative methods to estimate the early dispersion of contaminated sediment during the 20 months that Natural Product Library concentration followed the nuclear accident in those mountainous catchments exposed to a succession of erosive rainfall, snowfall and snowmelt events. It will also investigate, based on the radioisotopes identified, whether the accident produced geological records, i.e. characteristic properties in sediment deposit layers, that may be used in the future for sediment tracing and dating. The objective of the study that covered the period from November

2011 to November 2012 was to document the type and the magnitude of Methocarbamol radioactive contamination found in sediment collected along rivers draining the main radioactive pollution plume that extends over 20–50 km to the northwest of FDNPP in Fukushima Prefecture (Fig. 1a). For this purpose, we measured their gamma-emitting radionuclide activities and compared them to the documented surveys in nearby soils. In association with the U.S. Department of Energy (DOE), the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) performed a series of detailed airborne surveys of air dose rates 1-m above soils and of radioactive substance deposition (gamma-emitting) in the ground surface shortly after the nuclear accident (from 6 to 29 April 2011) in Fukushima Prefecture (MEXT and DOE, 2011).

Next we sought to establish if disrupting the VTA endocannabinoid

Next we sought to establish if disrupting the VTA endocannabinoid system alone is sufficient to decrease dopamine neurotransmission by infusing rimonabant directly into the VTA during reward seeking maintained in the ICSS task. As was found following systemic treatment, intrategmental rimonabant (200 ng i.c., unilateral)

significantly increased the latency to respond for brain stimulation reward (Figure 2E; MWU test, U = 0, p < 0.01; n = 8; mean values: b = 0.94, v = 1.10, rimo = 1.96 s) and decreased cue-evoked dopamine concentrations (Figure 2F; F(2,14) = 7.01, p < 0.01; 200 ng versus vehicle, p = 0.03; also see Figure S4A for mean dopamine concentration traces). The representative dopamine concentration traces (Figure 2G) show the effect of intrategmental rimonabant

on cue-evoked dopamine events in individual trials. Rimonabant-induced decreases in cue-evoked dopamine this website concentration during reward seeking maintained in the ICSS task can also be observed in audio-visual format (Movie S1). These data demonstrate that the VTA endocannabinoid system modulates dopamine signaling during the pursuit of brain stimulation reward. To assess whether disrupting endocannabinoid signaling also decreases dopamine transmission during the pursuit of natural reward, we treated animals with rimonabant while responding was maintained in an appetitive food-seeking task (Supplemental Experimental Procedures). Similar to the ICSS task, each lever response check details click here resulted in the delivery of food reinforcement and retraction of the lever for 10 s. After each 10 s timeout, a compound cue indicating reward availability was presented simultaneously with lever extension. Rimonabant decreased food seeking, as both a low (0.125 mg/kg i.v.; MWU test, U = 4, p = 0.03; n = 6) and high (0.3 mg/kg i.v.; MWU test, U = 0, p < 0.01; n = 8; mean

values: b = 1.45, v = 1.82, rimo = 17.7 s) dose increased response latency in comparison to vehicle treatment (Figure 3A). Rimonabant was administered prior to 60 responses, before animals reached satiety levels (avg. of 200 reinforced responses). As in the ICSS task, an increase in response latency was accompanied by a decrease in the concentration of cue-evoked dopamine release (Figure 3C; F(2,14) = 5.87, p < 0.01; 0.3 mg/kg versus vehicle, p = 0.04; also see Figure S2A for mean dopamine concentration traces). Rimonabant-induced decreases in cue-evoked dopamine concentration during individual (Figure 3D) and repeated (Figure 3E) trials are illustrated in pseudocolor. Likewise, intrategmental rimonabant-induced increases in response latency (Figure 3F; MWU test, u = 0, p < 0.01; n = 5; mean values: b = 1.18, v = 1.3, rimo = 2.75 s) were accompanied by a decrease in cue-evoked dopamine concentration (Figure 3G; F(2,14) = 9.86, p < 0.01; 200 ng versus vehicle, p = 0.014; also see Figure S4B for mean dopamine concentration traces).

In what follows, we refer to such results as cross-network intera

In what follows, we refer to such results as cross-network interactions. A major feature evident in Figure 2 concerns the dependence of BLP interactions on frequency band. Within-network correlations were weak and statistically

nonsignificant in the δ and θ bands. Significant within-network correlations were observed in the α (p < 0.01, FDR corrected), and even more Selleckchem SCH772984 so in the β band (p < 0.005, FDR corrected). No results are shown for the γ band because there were no identified MCWs in that frequency range. Among all RSNs, the DMN showed the strongest interaction with other networks, and this effect was especially clear in the β band (all contrasts p < 0.005, FDR corrected). Significant interactions (all contrasts p < 0.01, FDR corrected) were also observed in the α band. Other networks with significant cross-network interactions include the DAN (α, all contrasts,

p < 0.01 except versus language; β, all contrasts: p < 0.01) and the somatomotor network (α, all contrasts, p < 0.01 except versus visual; β, all contrasts, p < 0.01). VAN, language, and visual networks appeared relatively segregated. The analysis of cross-network interaction was extended to the level of single nodes, confining the analysis to the β band. Figure 3A shows the pairwise interaction matrix for all presently considered nodes (Table S1). Because the spatial resolution of source-space MEG is limited, correlation between closely spaced nodes is high. To minimize the impact of this effect, pairs of nodes closer than 35 mm were excluded (white cells in Figure 3). The 35 mm figure was derived below Duvelisib clinical trial from previous results (de Pasquale et al., 2010). However, the principal features evident in Figures 2 and 3 are insensitive to varying the node-pair proximity limit within a range of 0–100 mm (Figure S3). Five out of seven nodes of the DMN showed significant interactions with nodes of other networks in the β band (bar plots Figure 3A, all contrasts, p < 0.05). Among these nodes, the posterior cingulate cortex (PCC) showed the highest mean interaction with all other nodes (p < 0.001 Bonferroni corrected). Other significant nodes included

the left and right angular gyrus, and medial prefrontal cortex. In contrast, only two nodes of other networks reached a significant level of interaction: left posterior intraparietal sulcus, part of the DAN (p < 0.05, Bonferroni corrected), and the left central sulcus, part of the somatomotor network (p < 0.05, Bonferroni corrected). These findings, at the single node level, are consistent with results obtained by averaging over nodes within networks (Figure 2). Control analyses presented in Figure S4 show that both within or across-network interaction results are insensitive to choice of external node used to compute MCWs. A key finding of this study was that the results shown in Figures 2 and 3A reflect nonstationary phenomena.

, 2004) The interregional functional connectivity was obtained b

, 2004). The interregional functional connectivity was obtained by computing Pearson correlation coefficients for all possible this website pairs of ROIs. We computed statistical tests on all correlations after applying the Fisher Z-transform, which yields variates that are approximately normally distributed. The monkey sat in a customized primate chair, alone in

a completely dark room to avoid visual stimulation and minimize eye movements (Martinez-Conde et al., 2004). We acclimatized the monkey to this resting-state condition prior to recordings. The monkey had no behavioral requirements and was free to move his eyes (however, we analyzed epochs in which the eyes were stable, except for the correlation analyses on long data epochs, to allow comparison SCH772984 molecular weight with the literature). We monitored eye movements using a stationary eye-tracking system (Applied Science Laboratories) with an infrared camera operating at 120 Hz. The LFP from each electrode was amplified and band-pass filtered (3–300 Hz; precluding assessment of delta band oscillations) using

a preamplifier (PBX3/16sp-r-G1000/16fp-G1000, with a high input impedance headstage; Plexon) and Plexon Multichannel Acquisition Processor controlled by RASPUTIN software. The signals were digitized at a rate of 1,000 Hz. In total, 58 resting-state sessions (on separate days) were acquired from two monkeys (CA, 39 sessions; LE, 19 sessions). Analysis of LFPs. We performed data analyses in MATLAB using the Chronux toolbox ( Bokil et al., 2010). Preprocessing steps included the exclusion of artifacts

from any body movements and the removal of 60 Hz power signal peptide line noise and its harmonics using a notch filter (±1 Hz). We identified stable-eye epochs of at least 700 ms duration, during which the monkey’s eyes did not deviate by more than 2°. We calculated band-limited power (BLP) correlations and coherence in 500 ms windows within each stable-eye epoch after excluding (1) the first 200 ms of stable-eye epochs to remove any evoked responses, and (2) the 210 ± 141 ms (mean ± SD) before the next eye movement to remove any possible motor-related signals; if the stable-eye epoch spanned multiples of 500 ms (after excluding the first 200 ms of the epoch), each of these 500 ms data segments contributed to the analyses. BLP and Correlation Analysis. To examine BLP modulation in different frequency bands, we applied zero phase-shift band-pass filtering to the raw LFP signals to produce the following frequency bands: theta, 4–8 Hz; alpha, 8–13 Hz; beta, 13–30 Hz; and gamma, 30–100 Hz. We also probed effects at a higher-frequency resolution in the following bands: 4–8 Hz, 8–13 Hz, 13–20 Hz, 20–30 Hz, 30–40 Hz, 40–50 Hz, 50–60 Hz, 60–70 Hz, 70–80 Hz, 80–90 Hz, and 90–100 Hz. To normalize the resulting band-limited signals, we subtracted the mean power and divided by the SD for that frequency band.

David’s impact also extended to the culture at the MNI His warm,

David’s impact also extended to the culture at the MNI. His warm, easygoing, and informal style, underscored by his typical attire of a white shirt and blue jeans, resonated with all; he could often be found in the halls immersed in an animated conversation with security staff, housekeepers, and graduate students. Despite the demands of being Director, Dave sustained a vigorous research program. He and his collaborators demonstrated that cultured neurons readily formed presynaptic structures on synthetic beads coated with adhesive peptides (Lucido et al., 2009), opening new approaches for investigations of synaptogenesis.

An interesting twist Veliparib on this story is that these synapses are active and therefore suggest a potential mechanism to link neuronal signals to synthetic targets for the development of brain-machine interfaces. In another recent paper, Dave’s laboratory discovered a new role for nonprocessed Metformin procadherin molecules in the release of cancer cells from their substrates (Maret et al., 2010), raising prospects of novel therapeutic strategies, focused on cadherin

processing, to limit tumor cell invasion and metastasis. As these studies make clear, David had a wide ranging intellectual curiosity, with broad and varied scientific interests. He sought to look at scientific problems from a fresh vantage, ready to tilt against prevailing orthodoxy as necessary. He made additional contributions to investigations of the axon-glial junction (Dhaunchak et al., 2010 and Pedraza Sorafenib order et al., 2001) and the evolutionary origins of myelin. In collaboration with Boris Zalc, bolstered by field trips to the Muséum national

d’Histoire Naturelle (Paris), they inferred, based on the size of foramen in skulls of fossilized Paleozoic vertebrate fish, that myelin arose some 450 million years ago in placoderms, the first hinge-jawed fish (Zalc and Colman, 2000 and Zalc et al., 2008). In related studies, he collaborated with Dan Harline to examine the nature of the rapid, saltatory conduction in copepods as an example of convergent evolution (Hartline and Colman, 2007). He recently became interested in the poorly understood mechanism(s) by which the myelinating glial cell establishes the multilamellar compact myelin sheath around axons: one of the most striking structures in all of biology. The conventional view has been that the entire inner turn of the myelin sheath moves circumferentially around the axon. Based on a review of older EM studies and staining of markers at the axon-glial interface (Pedraza et al., 2009), David developed a provocative but still to be tested model that the glial cell initially spirals around the axon at each of its ends (akin to a chinese yo-yo, which he would bring to lectures to illustrate the point) and only later fills in the remainder of the glial membrane. Dave was an excellent communicator, which greatly enriched his science and aided his success as advocate and educator.