Animal Consciousness: Some Philosophical, Methodological, and Evolutionary Problems

No consensus exists concerning the mechanisms, distribution,or adaptive significance of consciousness. Agreement on anyone of these issues would aid in resolving others. Given a reliablebehavioral or neuroanatomical test for consciousness, we couldmap its distribution and describe its evolution. Conversely,if we knew its distribution, we could assess its adaptive valueand look for similarly distributed neuroanatomies to help usget at its mechanisms. Morgan's Canon—the rule that we should avoid attributinghumanlike mental states to other animals whenever possible—impedesthe use of the comparative method in unraveling this knot. Ifinterpreted in this context as a parsimony criterion, Morgan'sCanon is logically equivalent to epiphenomenalism. It is parsimoniousif and only if conscious mental events play no causal role inhuman behavior and human consciousness has no adaptive significance.Rejecting this conclusion entails rejecting the parsimony interpretationof Morgan's Canon.     

Mapping of the gene for anti-müllerian hormone to the short arm of human chromosome 19

The gene coding for human anti-Müllerian hormone (AMH) was localized to subbands p13.2----p13.3 on chromosome 19, using in situ hybridization and Southern blot analysis of a panel of man-mouse and man-hamster somatic cell hybrids.     

Regioselectivity in rat microsomal metabolism of benzo[a]pyrene: evidence for involvement of two distinct binding sites

The metabolic profile of benzo[a]pyrene (BP) in cumene hydroperoxide-(CHP)-dependent reaction by male rat liver microsomes was dependent on CHP concentration. At 0.05 mM CHP, 3-hydroxy-BP was the major metabolite. Increase in CHP reduced 3-hydroxy-BP formation but increased BP quinone formation simultaneously. This change in metabolic profile was reversed by preincubation with pyrene. Pyrene (PY) selectively inhibited quinone formation but enhanced 3-hydroxy-BP formation. Naphthalene (NP) had no effect on BP quinone formation but inhibited BP 3-hydroxylation. Phenanthrene (PA) and benz[a]anthracene (BA) inhibited effectively 3-hydroxy-BP formation but only slightly quinone formation. BP binding to microsomal protein correlated to quinone formation and not BP 3-hydroxylation. BP metabolism by female rat liver microsomes also depended on CHP concentration but was much less efficient than the male. Quinones were consistently predominant metabolites and their formation was also inhibited by pyrene. Our data provide evidence that regioselectivity in BP metabolism involves at least two distinct binding sites. One site recognizes the benzo region of BP in BP 3-hydroxylation and the other recognizes the pyrene region in quinone formation. The different ratios of 3-hydroxy-BP to quinone formation by male and female rat liver microsomes suggest that the two binding sites are probably located at separate cytochrome P-450 isozymes.     

Prepubertal treatment with estrogen or testosterone precipitates the loss of regular estrous cyclicity and normal gonadotropin secretion in adult female rats

To examine the effects of prepubertal steroid environment on subsequent estrous cyclicity and gonadotropin secretion, Silastic implants containing 25, 50 or 100% 17 beta-estradiol (E2;n=34), 50% diethylstilbestrol (DES; n=16) or 50% testosterone (T; n=17) were placed into female rats at 12 days of age and removed on the day of vaginal opening (18-24 days of age). At 80 days of age, the percentages of regularly cycling females in the E2-(three groups combined), DES- and T-implanted groups were 59%, 0% and 59%, respectively. By 110 days of age, the percentages were reduced to 24%, 0% and 0%, and at 140 days of age 6%, 0% and 0%, respectively. Many of these females displayed irregular estrous cycles followed by a persistent estrous (PE) state. By contrast, 89% of the control females (blank implants or no implant) maintained regular cycles up to 140 days of age. At 150 days of age, an i.p. injection of gonadotropin-releasing hormone (GnRH; 100 ng/100 g BW) markedly increased serum luteinizing hormone (LH), but not follicle-stimulating hormone (FSH), in intact PE females treated prepubertally with E2 implants. After the test with GnRH, PE rats were ovariectomized (OVX). Thirty days after OVX, similar GnRH administration significantly increased serum levels of both LH and FSH, but these responses were significantly (P less than 0.01) reduced when compared with those in OVX controls. Progesterone administration to estradiol benzoate-primed, acutely (3 days) OVX, or long-term (43 days) OVX-PE females did not increase LH or FSH release. These results indicate that exposure to exogenous estrogen or T prior to puberty precipitates the decline in estrous cyclicity associated with the loss of gonadotropin surge response, presumably due to an alteration in hypothalamic GnRH release.     

Radical Cations in Aromatic Hydrocarbon Carcinogenesis

Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species that bind covalently with cellular macromolecules to trigger the cancer process. Metabolic activation of PAH can be understood in terms of two main pathways: one-electron oxidation to yield reactive intermediate radical cations and monooxygenation to produce bay-region diol epoxides. The reason we have postulated that one-electron oxidation plays an important role in the activation of PAH derives from certain common characteristics of the radical cation chemistry of the most potent carcinogenic PAH. Two main features common to these PAH are: 1) a relatively low ionization potential, which allows easy metabolic removal of one electron, and 2) charge localization in the PAH radical cation that renders this intermediate specifically and efficiently reactive toward nucleophiles. Equally important, cytochrome P-450 and mammalian peroxidases catalyze one-electron oxidation. This mechanism plays a role in the binding of PAH to DNA. Chemical, biochemical and biological evidence will be presented supporting the important role of one-electron oxidation in the activation of PAH leading to initiation of cancer.     

Osteoarthritis of the hand in nonhuman primates: A clinical,radiographic, and skeletal survey of Cayo Santiago rhesus macaques

Abstract: We describe the relative prevalence and pattern of distribution of osteoarthritis (OA) in the hands of elderly (>15 years) rhesus macaques using clinical, radiographic, and skeletal examinations. In the clinical study the prevalence of nodes was 72% and 16% in the distal inter-phalangeal joints (DIPJ) and proximal inter-phalangeal joints (PIPJ), respectively, 31% of all monkeys had polyarticular nodes. Radiographic OA was present in 55%, 9.1%, and 0% of the DIPJs, PIPJs, and thumb bases, respectively. Skeletal OA as defined by joint surface eburnation for the DIPJ, PIPJ, and thumb base were 16%, 8%, and 2%, respectively. A similar pattern of hand OA with humans is described except for the thumb base OA. This may be due to the relatively rudimentary manipulative role of the macaque thumb. The finding of polyarticular nodal OA raises the possibility of a common pathogenensis for IPJ OA amongst primates.     

Efficient lipid-mediated transfection of DNA into primary rat hepatocytes

Cationic lipids are an effective means for transfecting nucleic acids into a variety of cell types. Very few of these lipids, however, have been reported to be effective with primary cells. We report on the efficacy of several commercially available cationic lipid reagents to transfect plasmid DNA into primary rat hepatocytes in culture. The reagents tested in this study include TransfectAce, LipofectAmine, Lipofectin, N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammoniumchloride (DOTMA), (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl-ammonium methylsulfate (DOTAP), and cetyltrimethyl-ammonium bromide/dioleoylphosphatidylethanol-amine (CTAB/DOPE). Electron micrographic (EM) studies indicate that similar size Lipofectin and DOTAP vesicles contain DNA-like material internally and that these vesicles attach to the cell membrane. DOTAP vesicles are multilamellar, appear as clusters, and have a high DNA-to-lipid ratio. Lipofectin vesicles appear to attach to the cell surface as individual vesicles. The EM observations are consistent with current theories on the mechanism of transfection by cationic lipids. While Lipofectin has proven to be effective in transfection studies of primary cells in culture, we have found DOTAP to be a viable alternative. DOTAP yields transfection rates in hepatocytes comparable to DOTMA and Lipofectin, however, at lower concentrations of reagent and at considerably less cost. Optimal conditions for transfecting 5 μg of plasmid DNA with DOTAP were achieved by utilizing multilamellar (vortexed) vesicles at a concentration of 15 μg DOTAP per 2 ml media in 60-mm plates for 2 h transfection time. In this study, DOTAP has proven to be economical, easy to prepare, and very effective in transfecting DNA into primary rat hepatocytes.