53 Furthermore, cross-sectional data suggest that muscle strength declines by approximately 15% per decade in the 6th and 7th decade, and 30% thereafter.54, 55, 56 and 57 Resistance training (RT) has increased its popularity among older adults because of its benefits on muscle fitness, body composition,

mobility, and functional capacity. More so, regular RT can offset the typical age-associated decline in bone health by maintaining or increasing BMD and total body mineral content.58 Although there is little question as to the benefits of RT in an older population, there is still some disparity regarding the ideal training volume (i.e., number of sets, repetitions, and load).59 and 60 Previous research has shown that older women who resistance train intensely (80% 1-RM) three times per week (whole-body RT, click here including elbow flexion and extension, seated row, overhead press, leg extension and curl, bench press, and sit ups) have similar improvements in FFM and total body strength. Hunter and colleagues61 demonstrated a 1.8-kg increase in FFM for the high-resistance group, compared to an increase of 1.9 kg for the variable-resistance group. Additionally, they observed a training effect for all 1-RM tests (seated press, 26.6%; bench press, 28.5%; arm curl, 63.7%; this website and leg press, 37.1%). Interestingly, those who trained with

a variable resistance demonstrated an increase in ease of performing daily tasks over those who trained intensely three times per week. These findings suggest that training too intensely or too frequently may result in increased fatigue and consequently a reduced training adaptation in older women due to insufficient time to recover. Low volume training (LV, 1 set per exercise) compared to high volume training (HV, 3 sets per exercise) performed twice a week for 13 weeks induced similar improvements in

maximal dynamic strength for knee extensors and elbow flexion, muscular activation of the vastus medialis and the biceps brachii, and muscle thickness for the knee extensors and elbow flexors in elderly women.62 The authors Resminostat suggest that during the initial months of training, elderly women can significantly increase upper- and lower-body strength by utilizing low volume training. However, after longer periods of training, larger muscle groups may require greater training volume to provide further strength gains.63 and 64 Allowing individuals to self-regulate their exercise intensity to a preferred intensity may lead to greater enjoyment and stronger compliance to an exercise program.65, 66 and 67 Additionally, it has been suggested that a low-intensity resistance exercise protocol may be more effective for older adults by increasing adherence rates.68 and 69 Compared to a high intensity resistance exercise program, lower attrition rates were observed when training used lower intensities (70% vs. 80% 1-RM) and frequencies (2 vs. 3 days).

, 2003). selleck chemicals On the other hand, the site-specific endoribonuclease function of IRE1 mediates the specific splicing of XBP-1 mRNA to generate an active (spliced) form XBP-1s (Calfon et al., 2002, Sidrauski and Walter, 1997 and Yoshida et al., 2001). XBP-1s targets a set of genes that increases the ER protein-folding capacity and facilitates

degradation of misfolded proteins (Lee et al., 2003 and Shaffer et al., 2004). Although IRE/XBP-1 has been proposed to be protective, the in vivo effect of XBP-1 on neuroprotection is less clear. In fact, it was shown that XBP-1 deletion in the nervous system (XBP-1flox/flox mice crossed with nestin-Cre mice) could extend lifespan of transgenic mice expressing a mutant SOD1, Selleck GW786034 an amyotrophic lateral sclerosis model, by enhancing autophagy, and thus degradation of the mutant SOD1 protein in vivo ( Hetz et al., 2009). In our analysis of the mechanisms for reduced protein synthesis ability in axotomized RGCs in adult mice (Park et al., 2008), we found that axotomized RGCs showed signs of UPR, indicating that ER stress is induced in these neurons. In fact, ER structures that are distributed along entire lengths of axons and are connected with those in the neuronal somas might possess the unique properties of transducing the

local axonal signals to the soma of individual neurons. However, despite previous reports about ER stress responses in neurons (Aoki et al., 2002 and Saxena et al., 2009), it is unknown how these pathways are activated and, more importantly, what the functional consequences are. Thus, we decided to assess axotomy-triggered UPR in depth using in vivo mouse models. CHOP, a key downstream target of PERK pathway, has been linked to apoptosis after ER stress in multiple disease models (Pennuto et al., 2008, Puthalakath et al., 2007, Silva et al., 2005, Song et al., 2008 and Zinszner

et al., 1998). To assess the expression of CHOP in intact and axotomized RGCs, we purified RGCs from wild-type rats with or without optic nerve crush by retrograde labeling and fluorescence-activated cell sorting (FACS) (Park et al., 2008). Through the use Parvulin of the mRNA isolated from purified RGCs, quantitative real-time PCR (qRT-PCR) analysis showed increased expression of CHOP and other ER stress markers, such as GADD45α (Lee et al., 2003), in axotomized RGCs (Figure 1A), which was further confirmed by both in situ hybridization and immunohistochemical analysis in retinal sections (Figures 1B and 1C). In contrast, Redd1/2, the inhibitors of the mTOR pathway induced by hypoxia (Brugarolas et al., 2004), and Hsp60, a mitochondria stress chaperone (Deocaris et al., 2006), were not induced by axotomy in RGCs (Figure 1A). We also examined the activation of other UPR targets in axotomized RGCs. Because XBP-1 splicing has been considered as a hallmark of UPR (Calfon et al.

This paradigm yielded a marked reduction in akinesia in all four limbs, but most notably in the contralateral arm to the stimulation site, as measured by accelerometers. Importantly, this adaptive closed-loop DBS successfully triggered a reduction of pallidal firing rate and a decrease of oscillatory activity in GPi (Rosin et al., 2011). The use of closed-loop DBS with motor cortex as the reference structure for triggering pallidal stimulation led to a reduction of stimulation frequency and also to an increase in the variability of the interstimulus interval when compared with standard

high frequency stimulation. Could the improvements observed simply reflect the fact that the stimulation pattern was of lower frequency and more irregular? Lapatinib research buy In order to demonstrate that the observed effects were due to the adaptive closed-loop nature of the stimulation, the authors performed two experiments. In one they applied an open-loop stimulation at low frequency (10 Hz versus standard DBS at 130 Hz). In another, they applied a stimulation pattern

based on previous recordings from M1, with the same variability as the online adaptive stimulation pattern, but unrelated to the ongoing activity at the moment of the stimulation. In both cases no relevant improvements in behavior or neuronal modulation were observed, strengthening the conclusion that it was HTS assay not the statistics of the stimulation pattern that promoted the behavioral improvements in closed-loop DBS, but rather the fact that the stimulation pattern reflected ongoing activity. This study offers important insights into how DBS works. Previous studies suggested that there is increased neural activity in the STN of MPTP-treated primates (Crossman et al., 1985). of Accordingly, lesioning the STN in the MPTP primate model reverted the Parkinson-like symptoms (Bergman et al., 1990). Since both electrical stimulation of STN and STN lesions produced amelioration of PD symptoms,

it was hypothesized that DBS leads to decreased activity in STN or decreased transmission from STN to GPi, therefore leading to reduced activity in GPi. Another suggestion has been that both STN lesions and DBS would disrupt the pathological oscillations observed in PD, leading to an improvement in motor symptoms; this view is supported by recent studies which suggest that DBS does not work by inhibiting STN neurons (Bar-Gad et al., 2004, Carlson et al., 2010 and Gradinaru et al., 2009). Interestingly, Rosin and colleagues uncovered that the application of a closed-loop protocol in which GPi activity triggered GPi stimulation resulted in a reduction in pallidal discharge rate with no change in GPi oscillatory activity, and even in an increase in oscillatory activity in motor cortex (Rosin et al., 2011).

However, the target choice signals Matsumoto and Takada observed occurred after the monkeys fixated the target but before delivery of the reward,

implying that these, too, encoded an expectation of reward. In fact, the same signals were present in trials where the monkeys made incorrect choices, consistent with the interpretation that they reflected monkeys’ subjective expectations rather than the reward outcome or a prediction error. The authors’ most intriguing finding resulted from an analysis of which neural responses were present in which cells. Although nearly all cells responded to the onset of the reward cue, cells responding to the sample stimulus were found almost entirely in dorsal and lateral regions of the midbrain, probably within the SNc. By contrast, find more cells responsive

to the size of the search array were more concentrated in medial and ventral ZD1839 in vivo regions, and there was a correlation between effect size and recording depth, most likely in the VTA. Such a gradient in function is broadly consistent with known anatomy: the SNc projects primarily to dorsolateral sensorimotor structures, whereas the VTA projects primarily to medial and limbic cortical areas associated with learning and motivation (Haber and Knutson, 2010). These observations endorse the authors’ conclusion that responses to the sample cue facilitate working memory by releasing dopamine in the dorsolateral prefrontal cortex. They are likewise consistent with the observation that factors influencing task difficulty are processed preferentially by systems responsible for calculating motivation and reward anticipation. old In addition to these tantalizing findings, the study also raises a number of important questions. Because the authors used spike waveforms to identify putative dopaminergic cells and recorded

only firing-rate responses, they could not verify the actual amount of dopamine released in response to task events; such verification could be provided by techniques such as voltammetry, which measures catecholamine release with millisecond precision. Furthermore, the difficulty of recording from small brainstem regions limited the number of cells recorded—enough so to suggest a gradient in function, perhaps, but the findings will benefit from replication. Finally, although both the location and timing of cell firing in response to the sample cue are consistent with the hypothesis that subsequent dopamine release facilitates working memory, future studies will need to verify this causally, perhaps by showing that selective activation or inactivation of lateral SNc neurons has an effect on the performance of working memory. What is most exciting about the work by Matsumoto and Takada is the finding that dopamine signaling in the brain is more heterogeneous and computationally specific than commonly thought.

The slow component of adaptation was slower in Tmc1Δ/Δ;Tmc2+/Δ cells than either Tmc1+/Δ;Tmc2Δ/Δ or Tmc1Bth/Δ;Tmc2Δ/Δ cells ( Figure 3E). The extent of adaptation also varied among the three genotypes ( Figure 3F). The differences in fast adaptation time constants may be a consequence of different calcium permeabilities ( Figure 2F) or they may Raf inhibitor reflect inherent differences in the adaptation properties of TMC proteins. Wu et al. (1999) modeled adaptation in auditory hair cells and suggested that fast

adaptation required a calcium binding site in close proximity to the channel pore. Thus, it is plausible that amino acid sequence differences between TMC1 and TMC2 may contribute to the different fast adaptation properties reported here. Because slow adaption

is thought to involve myosin motors ( Holt et al., 2002) at a remote location ( Wu et al., 1999), minor changes in calcium entry in cells this website bathed in 50 μM calcium may have little impact on the local calcium concentration at the slow adaptation site due to diffusion and the activity of calcium pumps and buffers. Another core property of an ion channel is its single-channel conductance. To examine contributions of TMC proteins to the properties of single transduction channels we designed a stimulation and recording paradigm. Inner hair cell bundles consist of an array of loosely organized stereocilia, with few lateral connections and the tallest row towering above the rest. To exploit this morphology, we engineered Phosphatidylinositol diacylglycerol-lyase stimulus pipettes that tapered to a few hundred nanometers in diameter at their distal tips which we used to deflect single stereocilia (Figure S4). We recorded the response of single stereocilium deflections in whole-cell mode at a holding potential of −84 mV. At this potential, voltage-dependent sodium and calcium channels were deactivated and we substituted Cs+ for K+ in the recording pipette to block residual potassium currents. The cells were bathed in an endolymph concentration of calcium, 50 μM, which had the dual effect of enhancing transduction current

amplitudes relative to standard extracellular calcium (i.e., minimizing calcium block) and prolonging channel open times by reducing calcium-dependent adaptation. We began with a characterization of Tmc1Δ/Δ;Tmc2Δ/Δ cells which lacked single-channel currents entirely and thus permitted evaluation of the recording paradigm in a quiescent background ( Figure 4A). We observed no voltage-dependent or ligand-gated ion channel activity. Under these conditions the root mean square (RMS) noise was 2.2 pA, which we reasoned would allow us to resolve currents with amplitudes greater than 4.4 pA. When we used this technique to record from Tmc1Δ/Δ;Tmc2+/Δ inner hair cells, we observed prominent single-channel currents ( Figure 4B) in response to small stereocilium deflections. The single-channel events were blocked by application of 0.

34 Due to the mean age (40 ± 5 years) and age range (29–46 years) of the participants, repeated measures analysis of covariance (ANCOVA) with age as a covariate were also used. However, as the covariate did not have a significant (p > 0.05) relationship to any of the outcome variables, only ANOVA data GABA pathway are reported. When a significant F-value was detected, data were subsequently

analysed using post hoc t tests with a Bonferroni correction. Between-group differences in baseline characteristics as well as intervention-induced changes were evaluated by a one-way ANOVA. Significance was selected at the level of p < 0.05. All statistical analyses were presented as mean ± SD unless otherwise stated. For the participants who completed the study (SG, n = 13, VG, n = 17; CO, n = 14), no group differences were present for the pre-intervention

baseline values ( Table 1). A significant group × time interaction was found for total fat percentage (p = 0.03; partial η2 = 0.15). Post hoc analysis revealed that in SG, fat percentage significantly decreased by 1.69% ± 2.38% (p = 0.03) during the 16-week intervention period, with no changes for VG or CO ( Fig. 1). A significant group × time interaction was also evident for fat mass of the trunk (p = 0.03; partial η2 = 0.16) and android (p = 0.04; partial η2 = 0.15). Post hoc analysis Navitoclax ic50 revealed that fat mass of the trunk and android (central fat predictive of body shape) significantly decreased by 1.02 ± 1.40 kg (p = 0.02) and 0.17 ± 0.27 kg (p = 0.04) respectively in SG over 16 weeks of training, with no changes for VG or CO ( Table 1). The changes in fat percentage (p = 0.03) for SG was significantly greater than for VG, as was the changes in fat mass of the trunk (p = 0.03) and android (p = 0.03). Lean mass was not significantly altered in any of the three groups following the 16-week intervention ( Table 1). During one-legged knee-extensor ramp exercise, a significant group × time interaction was

evident (p = 0.03; partial η2 = 0.18) for PCr depletion at the same time for the pre- and post-tests. In SG, after 16 weeks of training the degree of PCr depletion Rutecarpine was less (p = 0.04) (PCr content relative to baseline: 54.7% ± 12.5% vs. 59.1% ± 12.6% for pre- vs. post- training) with no change for VG or CO ( Table 2). Data for a representative participant is illustrated in Fig. 2. At the same time-point a significant main effect with time was seen for muscle pH but no significant interaction effects with group (SG: 6.95 ± 0.09 vs. 6.98 ± 0.07; VG: 6.95 ± 0.05 vs. 6.98 ± 0.06). Following 16 weeks of training, the rate of PCr recovery was not significantly altered after bouts of 24 s constant load exercise (SG; τ: 35.1 ± 8.7 vs. 30.7 ± 7.7 s; VG; τ: 32.8 ± 9.3 vs. 34.6 ± 9.6 s; CO; τ: 35.5 ± 8.8 vs. 32.7 ± 5.9 s, for pre- vs. post-training, respectively) in any of the groups.

, 2009), cell autonomous activation of PDF-R solely in PDF-negative pacemaker neurons with a membrane-tethered learn more PDF construct promotes strong rhythmicity in Pdf null flies, which would otherwise be poorly rhythmic ( Choi et al., 2012). Flies deficient in PDF or PDF-R display severe deficits in circadian rhythms and alterations in PER molecular rhythms during constant dark (DD) conditions. Among the four small LNvs, rhythms are maintained but become desynchronized (Lear et al., 2005; Lin et al., 2004). Among PDF target pacemaker groups like the LNd, the amplitude and period of the PER rhythm decrease but cells remain synchronized (Lin et al., 2004; Yoshii et al., 2009). Thus PDF neuropeptide acts over

many daily cycles to

promote the amplitude and pace of PER cycling—it has access to the molecular clockworks in diverse pacemakers and affects them differently. Recent observations have begun to shed light on the signaling pathways by which PDF affects synchronization and how these may differ according to cell type. Because PDF modulation system profoundly affects the circadian molecular oscillator within individual pacemaker neurons, the molecular this website details of the signaling pathway downstream of PDF-R gains in significance. Among the identified neurons in the pacemaker network, the PDF-expressing subset are termed M cells based on their abilities to influence “Morning” activity levels; several non-PDF pacemakers are termed E cells based on their abilities to influence “Evening” time activity levels (Grima et al., 2004; Stoleru et al., 2004; Yoshii et al., 2004; reviewed by Helfrich-Förster, 2009). Duvall and Taghert (2012) recently used an RNAi-mediated genetic approach to report that adenylate cyclase 3 (AC3) underlies PDF signaling in M cells. Surprisingly, disruption of AC3 does not alter PDF-R mediated others responses in non-PDF pacemakers (specifically, in the PDF-R(+) LNd). Moreover, AC3 disruptions in small LNv did not alter GPCR signaling by other ligands that elevate cAMP levels in these neurons (dopamine and the neuropeptide DH31). Hence, within small LNv, PDF-R

signaling occurs via discrete molecular pathways that are distinct from those controlled by other cAMP-elevating ligands. This provides a molecular mechanism underlying the observation that PDF-R activation in small LNv has potent effects on daily allocation of rest and activity, whereas DH31-R activation does not ( Choi et al., 2012). Furthermore, PDF-R association with a different AC(s) supports PDF signaling in the other circadian pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into “circadian signalosomes,” whose compositions differ between different pacemaker cell types ( Duvall and Taghert, 2012).

This suggests that these neurons

cannot simply inherit high temporal frequency tuning from the population we characterized in V1. Encoding for fast frequency information in higher areas could emerge from input from other areas (e.g., lateral posterior nucleus of the thalamus; Simmons et al., 1982), other populations within V1 (e.g., deeper cortical layers; Gao et al., 2010 and Kreile et al., 2011), or local circuits. Selleck PD-1/PD-L1 inhibitor To address the sharpness of TF tuning across areas, we examined tuning bandwidth. A bandwidth value was computed for bandpass cells as the half width at half max in octaves (Heimel et al., 2005; Figure S4). All extrastriate areas had higher mean TF bandwidth values than V1. This effect was significant for areas LM, AL, and RL (Figure S4, one-way ANOVA F(6,191) = 5.2, p < 0.005; post-hoc comparisons p < 0.05, HSD), and indicates that these areas tend to respond to a broader range of TFs than V1. The cumulative distributions of preferred SF for each area's population of neurons showed that all of the visual areas had populations encoding the spectrum of SFs tested. One group of areas—AL, RL, and LM—consisted of neurons preferring relatively low SFs (Figure 5A). Area AM contained neurons which preferred intermediate SFs, and areas V1, LI, and PM all showed high SF

Selleckchem BKM120 tuning. Areas LI and PM show particularly interesting distributions. LI contains a relatively large subset of neurons that prefer the lowest SF, similar to area AL. However, the remaining distribution deviates toward high SFs, suggesting the presence of separate populations of neurons in LI, preferring distinct ranges of SFs (Figure 5A, Figure S6). Area PM’s distribution also has an interesting pattern, with a small population of neurons Urease preferring low SFs which deviates rapidly toward a larger population preferring high SFs (Figure 5A, Figure S6).

We compared the geometric mean preferred SF across each population (Figure 5B) and found a main effect of visual area on preferred SF (one-way ANOVA, F(6,1783) = 59.7576, p < 0.0005). Post-hoc multiple comparisons tests revealed that areas LM, AL, RL, and AM all prefer lower SFs than V1 ( Figure 5B, p < 0.05, HSD), while areas LI and PM cannot be distinguished from V1 based on mean preferred SF. Area AL had the lowest preferred SF, significantly lower than areas V1, LM, LI, AM, and PM ( Figure 5B, p < 0.05, HSD). Only area RL showed comparably low preferred SF. Areas LM and AM showed similar, intermediate preferred SF ( Figure 5B). In the same manner as for TF tuning, we characterized neurons as lowpass, highpass or bandpass for SF (Figure 5C). Areas LM, LI, AL, and RL all had relatively high proportions of neurons which were lowpass, however the populations of neurons from these areas differed in other respects.

1 mRNA in dendrites (Raab-Graham et al., 2006), voltage-gated ion channels now join the rank of postsynaptic scaffolding proteins such as PSD-95 and SAPAPs, activity-dependent synaptic proteins such as CaMKIIα, Arc, and MAP1b, and ligand-activated ion channels such as GluR1/2 and GABAARδ (Bassell and Warren, 2008) as dendritic proteins with their mRNAs localized in neuronal dendrites and under the regulation of synaptic activity. FXS, the most common heritable mental retardation often associated with

autism, is caused by the loss of FMRP function GSK1120212 molecular weight (Bagni and Greenough, 2005). Our finding of Kv4.2 mRNA association with FMRP in neuronal dendrites and direct binding of FMRP to Kv4.2-3′UTR led us to discover that Kv4.2 is under

the control of FMRP. Whereas loss of FMRP resulted in no significant changes in Kv4.2 mRNA level or dendritic localization, it caused a dramatic increase of total Kv4.2 levels in the CA1 dendritic field selleck products of the hippocampus and in cultured hippocampal neurons from fmr1 KO mice. Similar elevation of Kv4.2 levels was also found for surface expression of Kv4.2, especially on distal dendrites, revealing FMRP suppression of Kv4.2 in vivo. Whereas we found elevated Kv4.2 in the hippocampal dendritic field of 3-week-old as well as 2-month-old fmr1 KO mice ( Figure 5A), a recent study reports Kv4.2 levels are reduced in fmr1 KO mice ( Gross et al., 2011), however, this conclusion is Sitaxentan based on Kv4.2 immunostaining that shows a different pattern from the documented Kv4.2 expression in stratum radiatum but low in stratum lacunosum moleculare ( Menegola and Trimmer, 2006) thus raising question about the specificity of the immunostaining. This study also reports that GFP-Kv4.2 3′ UTR is associated with mCherry-FMRP but not mCherry-RGG or other FMRP fragments that contain one or both RNA-binding domains ( Gross et al., 2011). In contrast, we found direct binding of Kv4.2 3′UTR to FMRP as well as its RGG-containing C-terminal domain ( Figures 3E–3G). Not only is FMRP required for suppression of dendritic Kv4.2, it is also essential for NMDAR-induced Kv4.2 protein production that enables Kv4.2

level to fully recover after its degradation and downregulation induced by NMDAR activation. FMRP thus plays a crucial role in tuning the dendritic Kv4.2 channel density and permitting dynamic regulation of Kv4.2 during synaptic activities. We found the elevated Kv4.2 level in fmr1 KO mice contributes to the LTP deficits ( Lauterborn et al., 2007), because the Kv4 channel blocker HpTx2 dose-dependently restored LTP induction by five theta bursts ( Figure 6). Given that hippocampal CA1 neurons lacking FMRP can exhibit LTP in response to strong stimuli (ten theta bursts) ( Lauterborn et al., 2007), Kv4.2 suppression by FMRP appears to be important for maintaining these neurons within the dynamic range for synaptic plasticity. Moreover, concurrent with NMDAR-induced Kv4.

He chaired one of the earliest Gordon Conferences on Myelin (1996), and his insights and support helped to establish these conferences as a major forum in this burgeoning field. Dave had an informal style that Ku0059436 sought to engage and challenge the audience, drawing on classical literature and popular culture to enliven his points. A recent lecture on the role serendipity plays in science, available online (http://muhc.ca/microscope-stethoscope/article/microscope-stethoscope-2006-lectures-three-princes-serendip-introduction-breakthroughs-resea),

highlights his gifts as a speaker. He was also pleased to playfully skewer pretensions. At a later Gordon Conference, he opened a talk with spectacular images of the universe newly revealed by the Hubble Telescope, beginning his lecture with, “Just in case you thought you were working on something really important. Dave was a serious wordsmith, dedicated to the craft of writing. He often cited the quote (usually attributed

to Blaise Pascal), “I apologize for writing such a long letter; I lacked the time to make it short.” Accordingly, his articles were typically tightly written and imaginatively illustrated (on occasion, doing double duty as covers of this journal). In scientific reviews, he was able to draw on studies in disparate fields to illuminate larger points (Colman, 1999 and Dustin and Colman, 2002). He used his pulpit at the MNI to pen engaging, topical articles for a general audience in his monthly Director’s Corner columns on subjects including breakthroughs in science, the process of discovery, MK-8776 datasheet global climate change, and advocating for science funding. In the belief that children should be exposed to science early on, he Casein kinase 1 initiated a project to develop an IMAX film on neuroscience specifically targeting a younger audience. Completion of this project will be a fitting memorial to his efforts to bring the excitement of science to students of all ages. However, for many of us, Dave was

more than a colleague we admired: he was a treasured and loyal friend. He was graciously available with sage advice on science, academic politics, and life. Dave was also terrific company and an excellent raconteur. He was a New Yorker by nature and nurture who referred to himself as a Jewish kid from the Bronx, with urbane interests in classical music, literature (particularly Shakespeare), cooking, and fine dining. He was also an avid collector and habitué of used bookstores and estate sales, amassing a collection of some 10,000 volumes of antique books, many on medicine and science. There was also “country” Dave, who loved his summer home in Maine. Here he would catch up on writing, but perhaps more importantly, he had the time and setting to indulge his interests in ornithology, astronomy, playing the banjo, and enjoying private family time, including stargazing with his daughters.