Laboratoire d'ethnologie et de sociologie comparative

Is there a universal hierarchy of the senses, such that some senses (e.g., vision) are more accessible to consciousness and linguistic description than others (e.g., smell)? The long-standing presumption in Western thought has been that vision and audition are more objective than the other senses, serving as the basis of knowledge and understanding, whereas touch, taste, and smell are crude and of little value. This predicts that humans ought to be better at communicating about sight and hearing than the other senses, and decades of work based on English and related languages certainly suggests this is true. However, how well does this reflect the diversity of languages and communities worldwide? To test whether there is a universal hierarchy of the senses, stimuli from the five basic senses were used to elicit descriptions in 20 diverse languages, including 3 unrelated sign languages. We found that languages differ fundamentally in which sensory domains they linguistically code systematically, and how they do so. The tendency for better coding in some domains can be explained in part by cultural preoccupations. Although languages seem free to elaborate specific sensory domains, some general tendencies emerge: for example, with some exceptions, smell is poorly coded. The surprise is that, despite the gradual phylogenetic accumulation of the senses, and the imbalances in the neural tissue dedicated to them, no single hierarchy of the senses imposes itself upon language.

Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes in glycosylation. We have previously used the said mouse model to look at O-linked glycosylation changes with breast cancer. In this glycan biomarker discovery study, we examined N-linked glycan variations during breast cancer progression of the mouse model but this time doubling the number of mice and blood draw points. N-glycans from total mouse serum glycoproteins were profiled using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry at the onset, progression, and removal of mammary tumors. We observed four N-linked glycans, m/z 1339.480 (Hex(3)HexNAc), 1485.530 (Hex(3)HexNAc(4)Fuc), 1809.639 (Hex(5)HexNAc(4)Fuc), and 1905.630 (Man(9)), change in intensity in the cancer group but not in the control group. In a separate study, N-glycans from total human serum glycoproteins of breast cancer patients and controls were also profiled. Analysis of human sera using an internal standard showed the alteration of the low-abundant high-mannose glycans, m/z 1419.475, 1581.528, 1743.581, 1905.634 (Man(6-9)), in breast cancer patients. A key observation was the elevation of a high-mannose type glycan containing nine mannoses, Man(9), m/z 1905.630 in both mouse and human sera in the presence of breast cancer, suggesting an incompletion of the glycosylation process that normally trims back Man(9) to produce complex and hybrid type oligosaccharides.

Ghrelin targets the hypothalamus to regulate food intake and adiposity. Endogenous ghrelin receptors [growth hormone secretagogue receptor (GHSR)] are also present in extrahypothalamic sites where they promote circuit activity associated with learning and memory, and reward seeking behavior. Here, we show that the substantia nigra pars compacta (SNpc), a brain region where dopamine (DA) cell degeneration leads to Parkinson's disease (PD), expresses GHSR. Ghrelin binds to SNpc cells, electrically activates SNpc DA neurons, increases tyrosine hydroxylase mRNA and increases DA concentration in the dorsal striatum. Exogenous ghrelin administration decreased SNpc DA cell loss and restricted striatal dopamine loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) treatment. Genetic ablation of ghrelin or the ghrelin receptor (GHSR) increased SNpc DA cell loss and lowered striatal dopamine levels after MPTP treatment, an effect that was reversed by selective reactivation of GHSR in catecholaminergic neurons. Ghrelin-induced neuroprotection was dependent on the mitochondrial redox state via uncoupling protein 2 (UCP2)-dependent alterations in mitochondrial respiration, reactive oxygen species production, and biogenesis. Together, our data reveal that peripheral ghrelin plays an important role in the maintenance and protection of normal nigrostriatal dopamine function by activating UCP2-dependent mitochondrial mechanisms. These studies support ghrelin as a novel therapeutic strategy to combat neurodegeneration, loss of appetite and body weight associated with PD. Finally, we discuss the potential implications of these studies on the link between obesity and neurodegeneration.

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Motor constraints on vocal production impose a trade-off between trill rate and frequency bandwidth within birdsong. We tested whether domesticated canary (Serinus canaria) females, reared either in acoustic isolation or in aviary conditions, had a preference for broad bandwidth songs with artificially increased syllable rates. The copulation solicitation display (CSD) was used as an index of female preference. As predicted, both naive and experienced females were especially responsive to syllables with a broad bandwidth emitted at an artificially increased rate. Female preference for supernormal stimuli provide support for the honest-signalling hypothesis and our results are consistent with recent findings indicating that production of song phrases maximizing both bandwidth and syllable rate may be a reliable indicator of male physical or behavioural qualities. We suggest that female preference for vocal emissions, which simultaneously maximize these two parameters, could be a widespread pattern within songbirds.

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microRNAs (miRNAs) regulate numerous physiological processes such as cell division and differentiation in many tissue types including stem cells. To probe the role that miRNAs play in regulating processes relevant to embryonic stem cell biology, we used RNA interference to silence DICER and DROSHA, the two main miRNA processing enzymes. Consistent with a role for miRNAs in maintaining normal stem cell division and renewal, we found that perturbation of miRNA pathway function in human embryonic stem cells (hESCs) attenuates cell proliferation. Normal cell growth can be partially restored by introduction of the mature miRNAs miR-195 and miR-372. These miRNAs regulate two tumor suppressor genes, respectively: WEE1, which encodes a negative G2/M kinase modulator of the CycB/CDK complex and CDKN1A, which encodes p21, a CycE/CDK cyclin dependent kinase inhibitor that regulates the G1/S transition. We show that in wild-type hESCs, WEE 1 levels control the rate of hESC division, whereas p21 levels must be maintained at a low level for hESC division to proceed. These data support a model for hESC cell cycle control in which miRNAs regulate negative cell cycle modulators at two phases of the cell cycle to ensure proper replenishment of the stem cell population.

CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment receptor. Here we show evidence that several group B Ads utilize an additional receptor for infection of human cells, which is different from CD46. We tentatively named this receptor receptor X. Competition studies with unlabeled and labeled Ads, recombinant Ad fiber knobs, and soluble CD46 and CD46 antibodies revealed three different subgroups of group B Ads, in terms of their receptor usage. Group I (Ad16, -21, -35, and -50) nearly exclusively uses CD46. Group II (Ad3, -7p, and -14) utilizes receptor X and not CD46. Group III (Ad11p) uses both CD46 and the alternative receptor X. Interaction of group II and III Ads with receptor X occurs via the fiber knob. Receptor X is an abundantly expressed glycoprotein that interacts with group II and III Ads at relatively low affinity in a Ca(2+)-dependent manner. This receptor is expressed at high levels on human mesenchymal and undifferentiated embryonic stem cells, as well as on human cancer cell lines. These findings have practical implications for stem cell and gene therapy.

BACKGROUND: Despite the extensive use of intrathecal morphine infusion for pain, no systematic safety studies exist on its effects in high concentrations. The authors assessed the effects of morphine and clonidine given 28 days intrathecally in dogs. METHODS: Beagles with lumbar intrathecal catheters received solutions delivered by a vest-mounted infusion pump. Six groups (n = 3 each) received infusions (40 microl/h) of saline or 1.5, 3, 6, 9, or 12 mg/day of morphine for 28 days. Additional groups received morphine at 40 microl/h (1.5 mg/day) plus clonidine (0.25-1.0 mg/day) or clonidine alone at 100 microg/h (4.8 mg/day). RESULTS: In animals receiving 9 or 12 mg/day morphine, allodynia was observed shortly after initiation of infusion. A concentration-dependent increase in hind limb dysfunction evolved over the infusion interval. Necropsy revealed minimal reactions in saline animals. At the higher morphine concentrations (all dogs receiving 12 mg/day), there was a local inflammatory mass at the catheter tip that produced significant local tissue compression. All animals with motor dysfunction displayed masses, although all animals with masses did not show motor dysfunction. The mass, arising from the dura-arachnoid layer, consisted of multifocal accumulations of neutrophils, monocytes, macrophages, and plasma cells. Inflammatory cells and endothelial cells displayed significant IL1beta, TNFalpha, iNOS, and eNOS immunoreactivity. No evidence of bacterial or fungal involvement was detected. There were no other changes in spinal morphologic characteristics. In four other groups of dogs, clonidine alone had no effect and in combination with morphine reduced the morphine reaction. CONCLUSIONS: The authors found that high intrathecal morphine concentrations lead to aseptic intrathecal inflammatory masses. The lack of effect of clonidine and the possible suppressive effects of clonidine on the local reaction suggest the utility of such coadministration.

Laboratory for Comparative Ethology; NICHD, NIH, DHHS; Poolesville, Maryland; Child Development Laboratory; Department of Human Development; University of Maryland; College Park, Maryland

In Brief Study Design. Experimental, human cadaveric study. Objective. To assess the fixation effects of injecting cement augmentation before screw insertion or after insertion of fenestrated screws; the effect of modulating cement viscosity; and the effects of these techniques on screw removal. Summary of Background Data. It seems clear that cement augmentation can enhance pedicle screw fixation in osteoporotic bone. What remains to be demonstrated is the aspects of optimal technique such that fixation is enhanced with the greatest safety profile. Methods. Part I: Human osteoporotic vertebrae were instrumented with solid (nonaugmented) screws, solid screws with polymethylmethacrylate (PMMA), partially cannulated fenestrated (Pfen) screws, or fully cannulated fenestrated (Ffen) screws through which PMMA was injected. Screw fixation was tested in pullout. Part II: Ffen screws were augmented with standard low-viscosity PMMA versus high-viscosity PMMA. Part III: Sample cohorts were extracted from vertebrae to assess required torque and characterize difficulty of extraction. Results. Part I: Pfen screws demonstrated the greatest fixation with mean failure force of 690 ± 182 N. All methods of cement augmentation demonstrated significant increases in screw fixation. Part II: Ffen screws did not demonstrate a significant difference in pullout strength when high-viscosity PMMA was used as compared with low-viscosity PMMA. Part III: Mean extraction torque values for solid augmented screws, Ffen screws, and Pfen screws were 1.167, 1.764, and 1.794 Nm, respectively, but these differences did not reach significance. None of the osteoporotic vertebrae sustained catastrophic failure during augmented screw extraction. Conclusion. Polymethylmethacrylate cement augmentation clearly enhances pedicle screw fixation in osteoporotic vertebrae when tested in pure pullout. The technique used for cement injection and choice of specialty screws can have a significant impact on the magnitude of this effect. Fenestrated screws have the capacity to confine cement placement in the vertebral body and may provide enhanced safety from cement extrusion into the spinal canal. It is feasible to inject high-viscosity PMMA through this fenestration geometry, and higher-viscosity cement may enhance the fixation effect. Experimental, osteoporotic cadaveric study comparing cement augmentation in solid and fenestrated pedicle screws. Polymethylmethacrylate cement augmentation clearly enhances pedicle screw fixation in osteoporotic vertebrae when tested in pure pullout. Fenestrated screws have the capacity to confine cement in the vertebral body. It is feasible to inject high-viscosity polymethylmethacrylate through this fenestration geometry, which may enhance the fixation effect.

Recently thecommonshas become a predominant metaphor for the types of social relationships between people, ideas, and new digital technologies. In IP debates, the commons signifies openness, the exclusion of intermediaries, and remix culture that is creative, innovative, and politically disobedient. This article examines the material and social implications of these debates (and the legal copyright regimes they interact with) in the translation andremixof Warumungu culture onto a set of locally produced DVDs. Although DVD technology can account for concerns such as monitoring access, preserving cultural knowledge, and reinforcing existing kinship networks, it also brings with it the possibility of multiple reproductions, knowledge sampling, and unintended mobilizations. Tracking the shifting mandates and emergent protocols in this digital interface redirects the lines of the debate to include multiple structures of accountability, ongoing systems of inequity, and overlapping access regimes involved in the always tense processes of cultural innovation.

Neurons in hibernating mammals exhibit a dramatic form of plasticity during torpor, with dendritic arbors retracting as body temperature cools and then regrowing rapidly as body temperature rises. In this study, we used immunohistochemical imaging and Western blotting of several presynaptic and postsynaptic proteins to determine the synaptic changes that accompany torpor and to investigate the mechanisms behind these changes. We show torpor-related alterations in synaptic protein localization that occur rapidly and uniformly across several brain regions in a temperature-dependent manner. Entry into torpor is associated with a 50-65% loss of synapses, as indicated by changes in the extent of colocalization of presynaptic and postsynaptic markers. We also show that the loss of synaptic protein clustering occurring during entry into torpor is not attributable to protein loss. These findings suggest that torpor-related changes in synapses stem from dissociation of proteins from the cytoskeletal active zone and postsynaptic density, creating a reservoir of proteins that can be quickly mobilized for rapid rebuilding of dendritic spines and synapses during the return to euthermia. A mechanism of neural plasticity based on protein dissociation rather than protein breakdown could explain the hibernator's capacity for large, rapid, and repeated microstructural changes, providing a fascinating contrast to neuropathologies that are dominated by protein breakdown and cell death.

Two groups of three German shepherd dogs each were inoculated with Leishmania chagasi or Leishmania donovani amastigotes and the infection was followed for 82 days. The dogs developed a persistent infection, became thin, and developed splenomegaly and lymphadenomegaly by 55 days after inoculation. All dogs developed a normocytic, normochromic anemia of increasing severity. Thrombocytopenia and leukopenia occasionally occurred. Blood tryptophan levels were decreased significantly in infected dogs. Increased total serum protein, with hypergammaglobulinemia and hypoalbuminemia, was present in all dogs to various degrees. There was a marked increase in gamma globulins, with smaller increases in alpha and beta globulins. Many of the clinicopathologic changes observed in these dogs were similar to the disease as it occurs in man. The German shepherd dog may be a useful laboratory model for the study of visceral leishmaniasis.

Many intracellular proteins are reversibly modified by O -linked GlcNAc ( O -GlcNAc), a post-translational modification that dynamically regulates fundamental cellular processes in response to diverse environmental cues. Accumulating evidence indicates that both excess and deficiency of protein O -GlcNAcylation can have deleterious effects on the cell, suggesting that maintenance of O -GlcNAc homeostasis is essential for proper cellular function. However, the mechanisms through which O -GlcNAc homeostasis is maintained in the physiologic state and altered in the disease state have not yet been investigated. Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O -GlcNAc–cycling enzymes O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA) at the transcriptional level. Specifically, we found that OGA promotes Ogt transcription through cooperation with the histone acetyltransferase p300 and transcription factor CCAAT/enhancer-binding protein β (C/EBPβ). To examine the role of mutual regulation of OGT and OGA in the disease state, we analyzed gene expression data from human cancer data sets, which revealed that OGT and OGA expression levels are highly correlated in numerous human cancers, particularly in pancreatic adenocarcinoma. Using a Kras G12D -driven primary mouse pancreatic ductal adenocarcinoma (PDAC) cell line, we found that inhibition of extracellular signal–regulated kinase (ERK) signaling decreases OGA glycosidase activity and reduces OGT mRNA and protein levels, suggesting that ERK signaling may alter O -GlcNAc homeostasis in PDAC by modulating OGA-mediated Ogt transcription. Our study elucidates a transcriptional mechanism that regulates cellular O -GlcNAc homeostasis, which may lay a foundation for exploring O -GlcNAc signaling as a therapeutic target for human disease.

This review brings together and discusses the significance of existing information about water-soluble (small molecule) organic phosphate constituents of red blood cells in different vertebrate species, with emphasis on 2,3 diphosphoglycerate (DPG), inositol pentaphosphate (IP5) ATP and guanosine triphosphate (GTP), compounds which may play an important role in respiratory physiology by modifying the affinity of hemoglobin for oxygen. Results on the distribution and concentration of these compounds in red cells of vertebrate animals can be summarized as follows 1) DPG High in mammals (except cats and ruminants) Absent in crocodilians squamata and fishes. High briefly in the bird embryo absent in adult. High briefly in turtle embryo low in juvenile low to absent in adult 2 IP5. High in birds. Absent in mammals, crocodilians squamata and fishes (with the exception of Arapaima gigas). Low in turtles 3 ATP Intermediate in mammals. High in birds and turtles. Very high in squamata Intermediate to very high in fishes. Low in crocodilians 4) GTP Very low in mammals birds, reptiles and amphibians (except for small pool in Rana tadpole). Low to very high in fishes.

This introductory essay reviews the literature on historical legacies in the post-communist area and relates it to the study of enlargement and Europeanisation. The authors develop a framework for the special section, specify various ways in which historical legacies can be conceived of affecting conditionality and compliance, give an overview of the contributions and summarise the findings.

Pepperberg, Irene Maxine. The Alex Studies: Cognitive and Communicative Abilities of Grey Parrots. Cambridge, MA: Harvard University Press, 1999. 446 pp. $39.95. Picture a dapper male, trimmed out in a gray garb, who is very talkative, knows a lot about a lot of things, and is named Alex. "Alex Trebek," you say. Well, yes, but in this case the "Alex" is actually a bird, an African grey parrot, to be precise. In 17 chapters, Dr. Irene Pepperberg, Alex's human mentor and scribe, takes the reader through the history of Alex's emergence as a parrot extraordinaire. The importance of this book, however, goes well beyond the demonstration of Alex's abilities to perform cognitive tasks and to communicate intelligently using human-like speech. Rather, it is the author's ability to weave her own work with Alex into the larger world of cognitive psychology that makes this an important contribution to the literature on comparative and cognitive studies. Given the well-documented differences in avian and mammalian neuroanatomy, the studies reviewed in this book provide further evidence for the remarkable convergence of behavioral and mental attributes in birds and mammals. Avian speech? No problem. Number-concept abilities equivalent to those shown in some great apes, such as same-different and larger-smaller? Such seems to be the case. Understanding and use of intention and referential mapping. Yup. Spontaneous intentional creativity, or "babbling"? Indeed. The list goes on, but there is enough here to clearly indicate that a large brain, or similarity of brain structure to that of humans, is not a requirement for intellectual abilities that are at least a match for those attributed to young humans, as well as some other mammals. How was it possible for bird-brained Alex to acquire and demonstrate these abilities? He does not seem to be unique, given that other grey parrots being studied in Dr. Pepperberg's lab also show at least the same early stages of cognitive skills that Alex showed at a comparable stage of training and testing. Rather, the author suggests that the acquisition of speech and speech understanding helps in the development of mental skills that are difficult to achieve without "language," even of this rudimentary sort. Pepperberg credits the use of a model-rival form of interactive training, developed and used in somewhat different form by some ethologists and comparative psychologists, with providing an optimal environment for allospecific (in this case, human-parrot) learning. Out of this training program emerged the ability of the human to teach the parrot in something approaching a pedagogical style. From pedagogy comes structured learning, facilitating the establishment of cultural norms and transmission of concepts from one individual, and generation, to the next. That is how it works for most humans, and that is how it seems to have worked for Alex. The success of Pepperberg with Alex, following a history of earlier, less successful attempts with other methods, suggests that optimal learning depends in large measure on the teacher finding the best approach to teaching. This factor is possibly at least as important as the brain machinery that the student brings to "class." It would be interesting to evaluate the success of a model-rival form of teaching in other animals, to determine whether success can be achieved in a wider comparative context. This author cites cases where this has been attempted, but the examples are few. "The Alex Studies" is organized chronologically as well as conceptually, with respect to Alex's training and successive layers of cognitive skills. The opening chapter relates the long history of human interest in talking with animals, typically in the form of legends that differed between different cultures, such as the ring that supposedly gave King Solomon this gift. This fascination with talking to animals carries forth to this day, as in the wizardly "Parseltongue" (the language used to talk to snakes) in the popular Harry Potter stories. In contemporary studies of animal communication, researchers working with some species have progressed to understanding the meaning of species-typical sounds and in some cases have "talked" with their species by playing back natural or synthetic copies of the species' own communication sounds. This research, although taking us a long way to understanding the communicative significance of natural sounds, has, nonetheless, been constrained by the apparently closed nature of animal communication systems. Pepperberg took another approach, that of teaching her experimental animal to learn to use "humanese" as a means of human-animal communication. This idea did not originate with Dr. Pepperberg, and the first chapter provides an overview of the earlier failures and less frequent successes. But Pepperberg did succeed. Chapter 2 tells how. The next eight chapters review various concepts that Alex has been tested for and the level of his proficiency in each. The ensuing six chapters then focus on Alex's and other grey parrots' vocal behavior, during formal testing and at other times. The final chapter discusses the implications of Alex's data. To summarize, The Alex Studies is not your traditional comparative psychology text but serves as a useful source for a course of studies on this topic, as well as being very readable by anyone with an interest in the use of animals in cognitive science. John D. Newman, Ph.D. Laboratory of Comparative Ethology; National Institute of Child Health and Human Development, NIH; Poolesville, Maryland

Résumé Si la féminisation du corps médical est désormais un phénomène massif dans tous les pays occidentaux, elle suscite des analyses quelque peu contradictoires. La plupart des études oscillent entre une posture « universaliste », supposant que les femmes médecins adopteront, à terme, les mêmes pratiques professionnelles que les générations précédentes, composées essentiellement d’hommes et une perspective d’inspiration « essentialiste », mettant largement l’accent sur les « spécificités » de l’exercice médical au féminin. Ici, nous montrons que les femmes médecins tendent effectivement à adopter des pratiques spécifiques, notamment en matière de gestion de l’interface vie familiale et vie professionnelle. Toutefois, ces soi-disant « spécificités féminines » sont de plus en plus souvent adoptées par des médecins hommes aussi. En effet, à partir du moment où ces hommes se trouvent en couple avec des femmes diplômées qui tiennent à rentabiliser leurs études sur le marché de l’emploi, il leur est tout aussi difficile de se conformer aux principes de « l’ethos » de la disponibilité permanente à l’égard des patients qui a longtemps prévalu dans cette profession en France. Si les hommes continuent de dominer les échelons supérieurs de la profession, ils n’échappent pas pour autant aux exigences de modification de leurs rapports à l’exercice médical et à la sphère domestique et familiale. L’analyse des dynamiques professionnelles exige donc une attention particulière à la dynamique du genre comme principe d’organisation de l’exercice médical.

BACKGROUND: Transitional cell carcinoma (TCC) of the urinary bladder of dogs can be a difficult cancer to treat, and effective therapies are limited. Vinblastine has been used in humans with TCC and has potent anti-proliferative effects against canine TCC cells in vitro. OBJECTIVES: To determine the antitumor activity and toxicoses of vinblastine in dogs with urinary bladder TCC. ANIMALS: Animals selected were 28 privately owned dogs that presented to the Purdue University Veterinary Teaching Hospital (PUVTH) with measurable, histologically confirmed TCC. METHODS: Prospective clinical trial: The starting vinblastine dosage was 3.0 mg/m(2) i.v. every 2 weeks. Treatment continued until cancer progression or unacceptable toxicoses occurred. Complete evaluations (physical exam, complete blood count [CBC], serum biochemical profile, urinalysis, thoracic radiography, abdominal ultrasound [US]) were performed at 8-week intervals. Urinary tract US with bladder tumor mapping was performed monthly. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. RESULTS: Tumor responses included 10 (36%) partial remission, 14 (50%) stable disease, and 4 (14%) progressive disease. The median progression free interval was 122 days (range, 28-399 days). The median survival time was 147 days (range, 28-476 days) from 1st vinblastine treatment to death and 299 days (range, 43-921 days) from diagnosis to death. The majority of dogs (27 of 28) did not have clinically relevant adverse effects. Seventeen of 28 (61%) dogs required dosage reductions because of neutropenia. CONCLUSION AND CLINICAL IMPORTANCE: Vinblastine has antitumor activity against TCC in dogs and can be considered another treatment option for this cancer.