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Reduced insulin-like growth factor 2 (IGF2) levels in Alzheimer’s disease (AD) may be the mechanism relating age-related metabolic disorders to dementia. Since Igf2 is an imprinted gene, we examined age and sex differences in the relationship between amyloid-beta 1–42 (Aβ42) accumulation and epigenetic regulation of the Igf2/H19 gene cluster in cerebrum, liver, and plasma of young and old male and female 5xFAD mice, in frontal cortex of male and female AD and non-AD patients, and in HEK293 cell cultures. We show IGF2 levels, Igf2 expression, histone acetylation, and H19 ICR methylation are lower in females than males. However, elevated Aβ42 levels are associated with Aβ42 binding to Igf2 DMR2, increased DNA and histone methylation, and a reduction in Igf2 expression and IGF2 levels in 5xFAD mice and AD patients, independent of H19 ICR methylation. Cell culture results confirmed the binding of Aβ42 to Igf2 DMR2 increased DNA and histone methylation, and reduced Igf2 expression. These results indicate an age- and sex-related causal relationship among Aβ42 levels, epigenomic state, and Igf2 expression in AD and provide a potential mechanism for Igf2 regulation in normal and pathological conditions, suggesting IGF2 levels may be a useful diagnostic biomarker for Aβ42 targeted AD therapies.

We examined measures of locomotor and anxiety-like behavior in male and female mice of 15 inbred strains on the elevated-plus maze, light/dark transition box and open field. Strain differences were found on all measures of locomotor activity and anxiety. Strain means for measures of locomotor activity on the three apparatus were significantly correlated, but strain means for commonly used measures of anxiety were not correlated. Principal component analysis revealed a common locomotor activity factor, which accounted for 28.6 % of the variance, but no common anxiety factor. Species-typical behaviors (defecations, stretch-attend postures, grooming) accounted for smaller proportions (

Most antipsychotics interfere with the dopaminergic system, resulting in extrapyramidal effects. This study compared the extrapyramidal effects of chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res), used as antipsychotics, in mice. Ninety age-matched male CD-1 strain of mice (25–33 g body weight) were divided into 3 groups, each consisting of 5 subgroups (n = 6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. Locomotor behaviour (open field test) and motor coordination (acceleratory rotarod) were assessed. Mice were also observed for 10 min for tremor and vacuous chewing movement (VCM). CPZ and Res dose-dependently decreased locomotor behaviour and impaired motor coordination (p < 0.01). RV also decreased locomotor behaviour (4.0 mg/kg; p < 0.05) but had minimal effect on motor coordination. VCM was lower in the RV group (0.17 ± 0.16/10 min) than the Res (6.8 ± 1.36/10 min) and Cpz groups (7.83 ± 1.95/10 min): F(4,25) = 10.703; p < 0.01. The frequency of bouts of tremor was also lower in the RV group (1.17 ± 0.72/10 min) than the Res (21.2 ± 5.63/10 min) and Cpz (7.83 ± 1.59/10 min) groups: F(4,25) = 11.012; p < 0.001. The root bark extract of R. vomitoria, therefore, has great potential in the management of psychotic disorders.

Network connectivity has become nearly ubiquitous, and the energy use of the equipment required for this connectivity is growing. Network equipment consists of devices that primarily switch and route Internet Protocol (IP) packets from a source to a destination, and this category specifically excludes edge devices like PCs, servers and other sources, and sinks of IP traffic. This paper presents the results of a study of network equipment energy use and includes case studies of networks in a campus, a medium commercial building, and a typical home. The total energy use of network equipment is the product of the stock of equipment in use, the power of each device, and their usage patterns. This information was gathered from market research reports, broadband market penetration studies, field metering, and interviews with network administrators and service providers. We estimate that network equipment in the USA used 18 TWh, or about 1% of building electricity, in 2008 and that consumption is expected to grow at roughly 6% per year to 23 TWh in 2012; world usage in 2008 was 51 TWh. This study shows that office building network switches and residential equipment are the two largest categories of energy use consuming 40% and 30% of the total respectively. We estimate potential energy savings for different scenarios using forecasts of equipment stock and energy use, and savings estimates range from 20% to 50% based on full market penetration of efficient technologies.

Neuroscientists associate the name of Donald O. Hebb with the Hebbian synapse and the Hebbian learning rule, which underlie connectionist theories and synaptic plasticity, but Hebb's work has also influenced developmental psychology, neuropsychology, perception and the study of emotions, as well as learning and memory. Here, we review the work of Hebb and its lasting influence on neuroscience in honour of the 2004 centenary of his birth.

Experimenters have often employed visual and/or spatial stimuli to assess rodent working memory in delayed (non)matching-to-sample or delayed response paradigms. We present an automated task that uses olfactory stimuli to test working memory in the rat. Rats were trained on a continuous delayed two-choice working memory task in an operant olfactometer with four different delays (3, 30, 60, and 120 sec). The rats required a mean of 12 sessions to achieve a criterion of 80% correct on two consecutive days with a 3-sec delay. Baseline data revealed a significant mnemonic function, with performance decreasing at the longer delays. Despite this significant effect, rats reached levels of approximately 76% correct at a retention interval (delay) of 120 sec. When a stable baseline level of performance was reached, the effect of the central muscarinic antagonist scopolamine hydrobromide was assessed. Scopolamine caused a dose-dependent, delay-independent decrease in performance. This result supports previous findings with scopolamine in other tests of rodent working memory and demonstrates the sensitivity of the two-choice olfactory task to this robust cognitive effect. A rodent working memory paradigm bearing closer resemblance to common human and nonhuman primate tests of working memory than do the often employed delayed response procedures [e.g., delayed (non)matching to position] may be highly valuable in the study of the biological substrates of short-term/working memory. The present experiment demonstrates the utility of the two-choice olfactory working memory task, which is sensitive to increasing delays and anti-cholinergic treatment and is rapidly acquired by rats.

MHC-congenic mice prefer to mate with mice of different MHC types and are able to discriminate between MHC-congenic mice by their urine odors, but nothing is known about behavioral differences among MHC-congenic mice. The present experiments examine the strain and sex differences in MHC-congenic C57BL/6J and B6-H-2K mice with respect to exploration and fear motivated behaviors in the elevated plus maze, the elevated zero maze, and the open field. In the elevated plus maze and elevated zero maze, C57BL/6J mice spent more time in the open areas than B6-H-2K mice, suggesting that they were less fearful and more exploratory. No sex differences for exploration were found but male mice defecated more than females in the elevated plus maze. In the open field there were no significant strain or sex differences in measures of exploration or fear. There were no strain differences in the investigation of a novel object placed into the open field, but males investigated the novel object more than females. These results indicate that there are differences in exploratory and fear behavior in MHC-congenic mice that may contribute to mate preferences and that behavioral differences in these mice might be further examined advantageously.

Behavioural studies of MHC‐congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117–158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC‐congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6‐H‐2bm1 and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6‐H‐2bm1 and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms.

Male Long-Evans rats were trained to discriminate between the urine odors of two congenic strains of rats (PVG and PVG.R1) in an olfactometer on a go/no-go operant task with water reinforcement. These odor donors differ genetically at only one locus of the major histocompatibility complex (MHC). The ability of the subjects to transfer their training to discriminate between novel individuals of the same MHC strain on the same and different diets was then examined. The subjects correctly generalized their original training to new samples from previously undiscriminated individuals of the same MHC type on the same diet without a significant drop in performance. A change in diet disrupted the perception of the MHC-related odor. In a second experiment, rats were trained to discriminate between the odors of pairs of genetically identical PVG or PVG.R1 rats on different diets and were tested for generalization using the odors of rats of the other strain (PVG.R1 or PVG) maintained on the same diet. Changing the strain of the odor donor did not disrupt the learned discrimination. The results of these two experiments confirm the ability of the MHC to generate constant cues in the urine but also reveal that variable diet cues disrupt the perception of these cues. The relationship between the MHC, diet, and other factors in determining individual odors is discussed.

A go/no-go operant task was used to assess the ability of male Long-Evans rats to discriminate between the urine odors from pairs of intact MHC congenic mice (C57BL/6-H-2Kb/J and C57BL/6-H-2Kbm1/ByJ), intact Y congenic mice (DBA1 and DBA1.C57BL10-Y), and castrated Y congenic mice of these two strains. The MHC congenic strains differ in alleles of the H-2 K locus, while the Y congenic strains differ in the nonrecombining part of the Y chromosome. Analysis of the number of correct responses to a criterion of 85% correct on each block of 20 trials revealed that the ability of the subjects to discriminate between urine odors did not differ whether samples were from pairs of intact MHC congenic mice, intact Y congenic mice, or castrated Y congenic mice. These findings are consistent with the hypothesis that individually unique urine odors may be influenced both by genes in the nonrecombining part of the Y chromosome and by genes in the major histocompatibility complex of chromosome 17. These odors are not androgen dependent. Such urinary chemical signals may be involved in pregnancy block (the Bruce effect), aggression, and other mouse social behaviors.

To determine the influence of genetic and microbiological factors in producing individually unique urine odors, we used a go/no-go operant task to assess the ability of eight male Long-Evans rats to discriminate between urine odors from the following pairs of male rats: (1) two outbred Long-Evans rats, (2) individual conventionally housed rats differing genetically only at the major histocompatibility complex (PVG vs. PVG.R1), (3) individual PVG versus PVG.R1 rats born by cesarean section and raised in germfree conditions, and (4) conventionally housed, genetically identical individuals of the PVG or PVG.R1 strains. Discriminable differences were present between the urine odors used in all four tasks. Analysis of the errors to a criterion of 85% correct discrimination responses revealed different learning patterns in each task. When bacteria were not present in genetically different rats (Task 3) and when bacteria were present but there were no genetic differences between rats (Task 4), the discrimination was the most difficult. The easiest discrimination involved the presence of bacteria and a genetic difference at the major histocompatibility complex (Task 2). These results indicate that, although bacteria are not necessary for the production of discriminable odor differences, they do influence the discriminability of the urine odors of rats.

Two experiments investigated the effects of isolation rearing on olfactory communication in rats. In Experiment 1, there were significant rearing and gender effects on the time spent investigating conspecific odors, the preferences for these odors, and the amount of urine marking over these odors by sexually naive male and female rats. Experiment 2 found significant effects of rearing condition and sexual experience on the responses of male rats to conspecific odors. In general, isolation rearing increased the time spent investigating conspecific odors, but reduced the amount of urine marking over these odors and altered the odor preference scales. These results suggest that the responses of both male and female rats to the odors of conspecifics are modified by rearing experience. The importance of learning conspecific odor signals for the development of normal social behavior is discussed.

A series of CNDO/2 molecular orbital properties were evaluated to determine their utility in parameterizing chemical reactivities. Some of these indices were used previously for only Π electron methods and were extended here to include the σ framework. Theoretical rationales were given for this extension to the semi-empirical all valence electron methods. Four systems, the aromatic hydrocarbons, the benzene derivatives, the substituted benzoic acids, and the substituted phenyl amines, were studied to test how well these indices can parameterize chemical reactivities. This study focused on reactions involving both σ and π electrons where the reactive site is not necessarily on the aromatic framework. For the nonplanar and heteropolar systems, these indices performed as well as the Huckel method did for the classical aromatics. These CNDO indices should perform effectively in multivariable regressions to parameterize the reactivities for more complicated problems such as those encountered in quantitative structure activity relationships of drugs.

The classical class I antigens of the major histocompatibility complex (MHC) are cell-surface glycoproteins which were originally discovered because they cause rapid rejection of cells or tissues grafted between unrelated individuals. These molecules are encoded by the K, D and L loci of the mouse MHC (and analogous loci in other species) which show extreme species polymorphism and a large number of alleles. In an outbreeding population 3.6 X 10(9) unique MHC class I phenotypes can be encoded by the 100 alleles at each of the K and D loci and the 6 alleles at the L locus. This level of polymorphism ensures that the cells and tissues of each unrelated individual are uniquely identified by their class I membrane-bound antigens. Like other membrane bound proteins, these class I molecules are anchored in the lipid bilayer by a hydrophobic domain encoded by exon 5. However, there have been reports of the occurrence of classical class I molecules in true solution in the blood of humans, mice, and rats. We report here that classical polymorphic class I molecules in normal rats are constitutively excreted in the urine and that untrained rats can distinguish the smell of urine samples taken from normal donors that differ only at the class I MHC locus and therefore excrete different allelomorphs of class I molecules in their urine.

Male offspring of stressed and control female rats were housed in pairs with a control male or a female from 22 to 90 days of age, then they were screened for infanticide and tested for parental behavior and sexual behavior. Male rats housed with females were less likely to be infanticidal than males housed with other males, but prenatal stress had no effect on infanticide rate. Control males housed with males showed a longer latency to carry pups than did males in the other three groups, and there was a stress × days interaction in the frequency of parental behavior, with prenatally stressed males showing more parental behavior than control males after 4 days of pup exposure. In the male sexual behavior tests, prenatally stressed males had longer intromission latencies and shorter postejaculatory intervals than did control males, while males housed with females had fewer mounts without intromissions and shorter ejaculation latencies than did males housed with other males. Female sexual behavior was not influenced by stress or housing, but control males showed more aggression toward stud males than did stressed males. Stressed male rats had smaller testes than did control males. Correlations among these measures indicate that prenatal stress results in a general syndrome of behavioral change.

A linear free energy relationship was found betweenvmax, the energy of the absorption maximum of chloride, bromide, or iodide ion in various solvents, and the α solvatochromic parameter which is a measure of the hydrogen bond donor ability of the solvent. The relationships are: for chloride,vmax=6.99α+50.16 kK; for bromide,vmax=5.52α+45.20 kK; for iodide,vmax=5.02α+40.33 kK. The correlation ofvmax for iodide ion with α gave a larger correlation coefficient and smaller standard deviation than a correlation with the ET(30) parameter of Dimroth. From the values ofvmax for iodide ion and the solvated electron in liquid ammonia at 25°C, these correlations indicate a preliminary value of 0.00 for the α parameter of liquid ammonia. This had not been reported before and is lower than expected from a general knowledge of the physical and chemical properties of liquid ammonia but is consistent with a more detailed consideration and recent gas phase measurements of hydrogen bond donor strength.