Differential transcriptome expression in human nucleus accumbens as a function of loneliness.

Loneliness is associated with impaired mental and physical health. Studies of lonely individuals reported differential expression of inflammatory genes in peripheral leukocytes and diminished activation in brain reward regions such as nucleus accumbens, but could not address gene expression in the human brain. Here, we examined genome-wide RNA expression in post-mortem nucleus accumbens from donors (N=26) with known loneliness measures. Loneliness was associated with 1710 differentially expressed transcripts and genes from 1599 genes (DEGs; false discovery rate P<0.05, fold change ⩾|2|, controlling for confounds) previously associated with behavioral processes, neurological disease, psychological disorders, cancer, organismal injury and skeletal and muscular disorders, as well as networks of upstream RNA regulators. Furthermore, a number of DEGs were associated with Alzheimer's disease (AD) genes (that was correlated with loneliness in this sample, although gene expression analyses controlled for AD diagnosis). These results identify novel targets for future mechanistic studies of gene networks in nucleus accumbens and gene regulatory mechanisms across a variety of diseases exacerbated by loneliness.

Bartonella clarridgeiae and Bartonella vinsonii subsp. berkhoffii exposure in captive wild canids in Brazil.

SUMMARY Wild canids are potential hosts for numerous species of Bartonella, yet little research has been done to quantify their infection rates in South America. We sought to investigate Bartonella seroprevalence in captive wild canids from 19 zoos in São Paulo and Mato Grosso states, Brazil. Blood samples were collected from 97 wild canids belonging to four different native species and three European wolves (Canis lupus). Indirect immunofluorescent antibody testing was performed to detect the presence of B. henselae, B. vinsonii subsp. berkhoffii, B. clarridgeiae, and B. rochalimae. Overall, Bartonella antibodies were detected in 11 of the canids, including five (12·8%) of 39 crab-eating foxes (Cerdocyon thous), three (11·1%) of 27 bush dogs (Speothos venaticus), two (8·7%) of 23 maned wolves (Chrysocyon brachyurus) and one (12·5%) of eight hoary foxes (Lycalopex vetulus), with titres ranging from 1:64 to 1:512. Knowing that many species of canids make excellent reservoir hosts for Bartonella, and that there is zoonotic potential for all Bartonella spp. tested for, it will be important to conduct further research in non-captive wild canids to gain an accurate understanding of Bartonella infection in free-ranging wild canids in South America.

Age-associated reduction of asymmetry in prefrontal function and preservation of conceptual repetition priming.

Older adults often show bilateral brain activation, compared to unilateral activation in younger adults, when performing tasks in domains of age-associated cognitive impairment, such as episodic and working memory. Less is known about activation associated with performance in cognitive domains that are typically unaffected by healthy aging. We used event-related functional magnetic resonance imaging to examine age-related patterns in brain activation associated with a form of implicit memory, repetition priming, which is typically preserved in healthy aging. Sixteen younger adults and 15 nondemented older adults performed semantic judgments (abstract/concrete) on single words in a study phase. In a test phase, identical judgments were made for repeated and new words. Younger and older adults showed similar response-time benefits (repetition priming) from repeated semantic classification. Repetition priming was associated with repetition-related reductions of prefrontal activation in both groups, but the patterns of activation differed between groups. Both groups showed similar activation reductions in dorsal left inferior prefrontal cortex (LIPFC), but older adults showed less reduction than younger adults in ventral and anterior LIPFC. Activation reductions were exclusively left-lateralized for younger adults, whereas older adults showed additional reductions in multiple regions of right frontal cortices. Right prefrontal activation reductions in older adults correlated with better repetition priming and better performance on independent tests of semantic processing. Thus, reduced asymmetry of prefrontal activation reductions in healthy aging was related to conceptual repetition priming, a form of learning that is spared in aging, and with the sparing of semantic memory.

Cyclic nucleotide phosphodiesterase: high activity in a mammalian photoreceptor.

Purified outer segments of bovine rods exhibit phosphodiesterase activity against adenosine and guanosine cyclic 3',5'-monophosphates (cyclic AMP and cyclic GMP). The enzyme hydrolyzed cyclic GMP more rapidly than cyclic AMP at low substrate concentrations. The presence of high phosphodiesterase activity in this highly specialized organelle suggests that this enzyme may function in control of cyclic nucleotide concentration during visual excitation or adaptation.

Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology.

BACKGROUND AND PURPOSE: The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. MATERIALS AND METHODS: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-ß load within the entorhinal cortex and medial temporal and neocortical regions. RESULTS: We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex (P = .09) and medial temporal lobe amyloid-ß (P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles (P = .003) and amyloid-ß (P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex (P = .31) and medial temporal lobe tangles (P = .051). CONCLUSIONS: Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.

Long-term memory in Alzheimer's disease.

Recent findings have further characterized the neural and psychological bases of long-term memory failure in Alzheimer's disease. Convergent volumetric neuroimaging studies indicate that loss of episodic memory is specifically related to early-stage limbic-diencephalic pathology, and that non-mnemonic impairment is specifically related to later-stage temporal-neocortical pathology. Recent studies of Alzheimer's disease have also reported informative cognitive dissociations in semantic memory and implicit memory.

Association of guanylate cyclase with the axoneme of retinal rods.

Axonemes were isolated from purified bovine retinal rod outer segments by dissolving the outer segment membranes in detergent and separating the axonemes by centrifugation on a linear detergent-containing sucrose density gradient. Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.61.2) activity was concentrated in the axoneme fraction. Guanylate cyclase eluted in the void volume when detergent-solubilized rod outer segments were subjected to exclusion chromatography on Sepharose 4B. Attempts to extract guanylate cyclase from isolated axonemes with salt, EDTA, base and other reagents were successful.

Oxygen dependence of photosynthetic electron transport in a bacteriochlorophyll-containing rhizobium.

Bacteriochlorophyll-containing rhizobia, which form nitrogen-fixing nodules on the stems and roots of the legume Aeschynomene, grow photosynthetically only in the presence of oxygen or auxiliary electron acceptors. We show that, in whole cells of the Rhizobium strain BTAi 1, a single-turnover excitation flash photooxidized c-type cytochrome under aerobic but not anaerobic conditions. Light-induced fluorescence yield changes show that under anaerobic conditions, the primary acceptor quinone, Q(A), is predominantly in the reduced state and so unable to accept electrons. Thus, as is the case for the aerobic photosynthetic bacterium Roseobacter denitrificans, over-reduction of Q(A) likely prohibits photosynthesis under anaerobic conditions.

Word-stem completion priming for perceptually and conceptually encoded words in patients with Alzheimer's disease.

This study examined whether the frequently reported word-stem completion priming deficit of Alzheimer's disease (AD) patients could be characterized as either a semantic encoding deficit or a conceptual priming deficit. AD patients and normal elderly control subjects studied words in two conditions: (1) reading visually presented words aloud, which maximizes perceptual encoding of seen words, and (2) generating words aloud from definitions, which maximizes conceptual encoding of words not seen but retrieved on the basis of semantic context. Recognition accuracy was greater for words that were generated at study, and word-stem completion priming was greater for words that were read at study. For the AD patients, recognition accuracy was impaired and word-stem completion priming was intact for words encoded in both conditions. The findings are discussed in terms of discrepant results about word-stem completion priming in AD.

Convergent behavioral and neuropsychological evidence for a distinction between identification and production forms of repetition priming.

Four experiments examined a distinction between kinds of repetition priming which involve either the identification of the form or meaning of a stimulus or the production of a response on the basis of a cue. Patients with Alzheimer's disease had intact priming on picture-naming and category-exemplar identification tasks and impaired priming on word-stem completion and category-exemplar production tasks. Division of study-phase attention in healthy participants reduced priming on word-stem completion and category-exemplar production tasks but not on picture-naming and category-exemplar identification tasks. The parallel dissociations in normal and abnormal memory cannot be explained by implicit-explicit or perceptual-conceptual distinctions but are explained by an identification-production distinction. There may be separable cognitive and neural bases for implicit modulation of identification and production forms of knowledge.

Font-specific priming following global amnesia and occipital lobe damage.

Font-specificity in visual word-stem completion priming was examined in patients with global amnesia and Patient M.S., who had a right-occipital lobectomy. Word-stems appeared in the same or different font as study words. Amnesic patients showed normal font-specific priming (greater priming for words studied in the same than different font as test), despite impaired word-stem cued recall. Patient M.S. failed to exhibit font-specific priming, despite preserved declarative memory. Therefore, perceptual specificity in visual priming depends on visual processes mediated by the right-occipital lobe rather than medial temporal and diencephalic regions involved in declarative memory.

Word-stem completion priming in healthy aging and Alzheimer's disease: the effects of age, cognitive status, and encoding.

There are many conflicting results concerning the effects of age and Alzheimer's disease (AD) on word-stem completion priming. To examine potential sources of this variability, the authors examined the influences on such priming of age, cognitive status, and encoding in a large sample of young, old, and AD individuals. At study, words were processed aloud by reading, reading and rating likeability, or generating from definition. Old participants had less priming than young participants and more priming than AD patients. For the healthy old participants, priming decreased with advancing age and with cognitive loss following generation only. For AD patients, priming decreased as dementia severity increased; patients with the mildest dementia did not differ from healthy old participants. Thus, age, cognitive status, and encoding differentially influenced the magnitude of priming in healthy aging and AD.

Preserved priming across study-test picture transformations in patients with Alzheimer's disease.

Picture-naming priming was examined across different study-test transformations to explore the nature of memory representations of objects supporting implicit memory processes in patients with Alzheimer's disease (AD). Although severely impaired in explicit memory for pictures and words, AD patients demonstrated normal priming across perceptual transformations in picture orientation (Experiment 1) and picture size (Experiment 2) and across symbolic transformations from words to pictures (Experiment 3). In addition, the priming across alterations in picture size was invariant. This demonstrates that AD patients have preserved implicit memory for high-level, abstract representations of objects.

Intact and impaired conceptual memory processes in amnesia.

To examine the status of conceptual memory processes in amnesia, a conceptual memory task with implicit or explicit task instructions was given to amnesic and control groups. After studying a list of category exemplars, participants saw category labels and were asked to generate as many exemplars as possible (an implicit memory task) or to generate exemplars that had been in the prior study list (an explicit memory task). After incidental deep or shallow encoding of exemplars, amnesic patients showed normal implicit memory performance (priming), a normal levels-of-processing effect on priming, and impaired explicit memory performance. After intentional encoding of exemplars, amnesic patients showed impaired implicit and explicit memory performance. Results suggest that although amnesic patients can show impairments on implicit and explicit conceptual memory tasks, their deficit does not generalize to all conceptual memory tasks.

Neuropsychological dissociation between recognition familiarity and perceptual priming in visual long-term memory.

The present study examined whether the same brain region mediates visual-perceptual repetition priming and a familiarity component of visual recognition memory. In two experiments, familiarity-based recognition was measured in an individual (M.S.) with impaired visual repetition priming due to a lesion of right occipital cortex. In both experiments, M.S. demonstrated intact recognition familiarity despite his visual nondeclarative memory impairment. These results converge with other behavioral results to indicate that recognition familiarity does not depend on the same memory system that mediates perceptual priming.

Repetition priming in normal aging and Alzheimer's disease: a review of findings and theories.

On repetition priming tasks, memory is measured indirectly as a change in performance due to recent experience. It is often functionally and neurally dissociated from performance on explicit memory tasks, which directly measure conscious recall or recognition of recent events. Repetition priming has therefore been extensively studied in normal aging and Alzheimer's disease, which feature mild to severe changes in explicit memory. Initial studies indicated that repetition priming was immune to the effects of aging and greatly reduced in Alzheimer's disease (AD). As more studies have been performed, however, these initial conclusions appear less clear than before and, in the case of AD, actually misleading. The purpose of this article is to provide a comprehensive review of this rapidly expanding literature, articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings.