Evidence for adult age-invariance in associative false recognition.

Older people are more prone to memory distortions and errors than young people, but do not always show greater false recognition in the Deese-Roediger-McDermott (DRM) task. We report two preregistered experiments investigating whether recent findings of age-invariant false recognition extend to designs in which studied items are blocked. According to (Tun, P. A., Wingfield, A., Rosen, M. J., & Blanchard, L. (1998). Response latencies for false memories: Gist-based processes in normal aging. Psychology and Aging, 13(2), 230-241.), age effects on false recognition in the DRM task are due to a greater reliance on gist processing which is enhanced under blocked study conditions. Experiment 1 assessed false recognition in an online variant of the DRM task where words were presented visually, with incidental encoding. The results showed Bayesian evidence against greater false recognition by older adults, whether lures were semantically associated with studied lists, or perceptually related (presented in the same distinctive font as studied lists) or both. Experiment 2 used a typical DRM procedure with auditory lists and intentional encoding, closely reproducing (Tun, P. A., Wingfield, A., Rosen, M. J., & Blanchard, L. (1998). Response latencies for false memories: Gist-based processes in normal aging. Psychology and Aging, 13(2), 230-241.) Experiment 2 but omitting an initial test of recall. The results showed evidence against an age-related increase in critical lure false recognition under these conditions. Together, the data suggest that older people do not make more associative memory errors in recognition tests than young people.

Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses.

Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo. Inhibition of SFK activity not only alters TLR-ligand localization and inhibits downstream signalling events, but, independent of ex-vivo TLR stimulation, also affects constitutive phosphorylation of BCAP, an adaptor protein bridging PI3K and TLR pathways. Our data identify Fyn and Lyn as important factors that promote pDC responses, describe the mechanisms involved and highlight a tonic SFK-mediated signalling that precedes pathogen encounter, raising the possibility that small molecules targeting SFKs could modulate pDC responses in human diseases.

Effects of herbal preparations on symptom clusters during the menopausal transition.

AIMS: To determine the effects of herbal therapies on hot flushes and at least one other symptom including, sleep, mood, cognition, and pain that women experience during the menopausal transition and early postmenopause. METHODS: An extensive search of PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for randomized, controlled trials reported in English between January 2004 and July was conducted by an experienced reference librarian. There were 1193 abstracts identified but only 58 trials examined effectiveness of therapies for hot flushes and at least one additional co-occurring symptom. RESULTS: Seventeen studies used herbal preparation including seven studies of black cohosh, two studies of black cohosh mixed with other herbals, and eight studies of other herbals. Of these, one study of black cohosh, two studies of black cohosh mixed with other herbals, and four other herbal studies had significant effects on hot flushes and at least one additional co-occurring symptom. The adverse events of herbal therapies were various, ranging from mild to moderate and women were generally tolerant of the preparations. CONCLUSIONS: Black cohosh mixed with other herbals, Rheum rhaponticum, and French maritime pine bark had significant effects on hot flushes and at least one other symptom. These herbal therapies may be a promising alternative treatment to hormonal treatment. Future studies should classify women based on their menopausal stages, report each symptom separately, have adequate sample size, focus on multiple co-occurring symptoms, and target symptom management of menopausal symptoms.

Effects of traditional Chinese medicine on symptom clusters during the menopausal transition.

AIMS: To review controlled clinical trials of traditional Chinese medicine (TCM) therapies for hot flushes and at least one other co-occurring symptom among sleep, cognitive function, mood, and pain. METHODS: An experienced reference librarian performed an extensive search of PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for randomized, controlled trials reported in English between 2004 and July 2011. Of 1193 abstracts identified, 58 trials examined effectiveness of therapies for hot flushes and at least one additional co-occurring symptom. RESULTS: Eleven trials (13 publications) examined TCM therapeutics of acupuncture, Chinese herbal medicine (CHM) or moxibustion. Acupuncture trials (eight) yielded mixed results; five trials significantly reduced hot flushes. Of those five trials, one also showed benefit for sleep and pain and two trials found benefit for mood symptoms. Of three CHM trials, three trials had significant findings: one for hot flushes and mood, one for hot flushes and pain, and one for hot flushes, sleep, mood symptoms and pain. Moxibustion and counseling (one trial) significantly reduced hot flushes, mood symptoms and pain. None of the trials reported any serious adverse events. CONCLUSIONS: TCM therapeutics of acupuncture, CHM and moxibustion show promising results for the treatment of mood and pain symptoms co-occurring with hot flushes. Although the controlled clinical trials of TCM therapeutics reviewed here measured multiple symptom outcomes, few report treatment effects in ways that allow clinicians to consider symptom clusters when prescribing therapies. Future studies need to measure and report results for individual symptoms or group like symptoms together into subscales. Controlled clinical trials with larger numbers of participants are essential to allow evaluation of these therapies on hot flushes and multiple co-occurring symptoms.

Effects of mind-body therapies on symptom clusters during the menopausal transition.

AIMS: Although most women experience symptom clusters during the menopausal transition and early postmenopause, investigators reporting clinical trial effects for hot flushes often omit co-occurring symptoms. Our aim was to review controlled clinical trials of mind-body therapies for hot flushes and at least one other co-occurring symptom from these groups: sleep, cognitive function, mood, and pain. METHODS: An experienced reference librarian performed an extensive search of PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for randomized controlled trials reported in English between 2004 and July 2011. Of 1193 abstracts identified, 58 trials examining effectiveness of therapies for hot flushes and at least one additional co-occurring symptom of interest were identified. RESULTS: Eight trials (ten publications) examined relaxation, yoga, or exercise. Physical activity/exercise trials (six) yielded mixed results; only one significantly reduced hot flushes and mood symptoms. Of two relaxation therapy trials, only mindfulness-based stress reduction training reduced sleep and mood symptoms and had within-group treatment effects on hot flushes. Yoga (one trial) significantly reduced hot flushes and improved cognitive symptoms more than exercise, and also had within-group effects on sleep and pain symptoms. CONCLUSIONS: Studies of mind-body therapies for hot flushes increasingly measure multiple symptom outcomes, but few report treatment effects in ways that allow clinicians to consider symptom clusters when prescribing therapies. Future studies need to measure and report results for individual symptoms or group like symptoms together into subscales rather than use subscales with mixed dimensions. Trials with larger numbers of participants are essential to allow evaluation of these therapies on multiple co-occurring symptoms.

Luminescence techniques and characterization of the morphology of polymer latices 2. Fluorescence lifetime, phosphorescence and fluorescence anisotropy studies.

Five poly(n-butyl methacrylate), PBMA, latex dispersions have been prepared, each incorporating a different fluorescent label, via a two-stage seeded emulsion polymerization. The resultant latices contain ca. 35% by weight total solids and are of 80 (+/-10) nm diameter as determined by photon correlation spectrometry. Luminescence spectroscopic techniques, namely fluorescence (and phosphorescence) excited state lifetime measurements in addition to time-resolved anisotropy experiments have provided useful information regarding the morphology, microviscosity and water permeability of the resultant particles. A picture of the PBMA colloid emerges of an interior which is highly viscous and water impermeable in nature. Indeed, the environment is protective enough to sustain room temperature stabilized phosphorescence from both an acenaphthylene and 9-phenanthrylmethyl methacrylate labeled dispersion through simple nitrogen purging of the solutions. However, the current spectroscopic measurements should be viewed with the knowledge that each luminescent label may fashion its own distinctive microenvironment within the latex during polymerization.

Luminescence techniques and characterization of the morphology of polymer latices. 3. An investigation of the microenvironments within stabilized aqueous latex dispersions of poly(n-butyl methacrylate) and polyurethane.

Fluorescence techniques (including time-resolved anisotropy measurements, TRAMS) have been used to probe differences in morphology between two stabilized aqueous latex dispersions (poly(n-butyl methacrylate), PBMA, and polyurethane, PU). Use of the emission characteristics of probes such as pyrene and phenanthrene dispersed within particles reveals that the PU latices are more heterogeneous in nature: evidence exists, particularly from quenching measurements and TRAMS, that voids and channels of water permeate the PU structure, resulting in a relatively soft, open particle, swollen by ingress of the bulk aqueous phase. Fluorescence measurements indicate that PBMA colloids, however, are composed of relatively hard, hydrophobic particles. In addition, TRAMS are considered to be a valuable tool both for probing the morphological characteristics of such dispersions and in estimating the average particle size.

Topography of projections from amygdala to bed nuclei of the stria terminalis.

A collection of 125 PHAL experiments in the rat has been analyzed to characterize the organization of projections from each amygdalar cell group (except the nucleus of the lateral olfactory tract) to the bed nuclei of the stria terminalis, which surround the crossing of the anterior commissure. The results suggest three organizing principles of these connections. First, the central nucleus, and certain other amygdalar cell groups associated with the main olfactory system, innervate preferentially various parts of the lateral and medial halves of the bed nuclear anterior division, and these projections travel via both the stria terminalis and ansa peduncularis (ventral pathway). Second, in contrast, the medial nucleus, and the rest of the amygdalar cell groups associated with the accessory and main olfactory systems innervate preferentially the posterior division, and the medial half of the anterior division, of the bed nuclei. And third, the lateral and anterior basolateral nuclei of the amygdala (associated with the frontotemporal association cortical system) do not project significantly to the bed nuclei. For comparison, inputs to the bed nuclei from the ventral subiculum, infralimbic area, and endopiriform nucleus are also described. The functional significance of these projections is discussed with reference to what is known about the output of the bed nuclei.

Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems.

The expression of innate reproductive, defensive, and ingestive behaviors appears to be controlled by three sets of medial hypothalamic nuclei, which are modulated by cognitive influences from the cerebral hemispheres, including especially the amygdala and hippocampal formation. PHAL analysis of the rat amygdala indicates that a majority of its cell groups project topographically (a) to hypothalamic behavior systems via direct inputs, and (b) to partly overlapping sets of hypothalamic behavior control systems through inputs to ventral hippocampal functional domains that in turn project to the medial hypothalamus directly, and by way of the lateral septal nucleus. Amygdalar cell groups are in a position to help bias or prioritize the temporal order of instinctive behavior expression controlled by the medial hypothalamus, and the memory of associated events that include an emotional or affective component.

Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats.

OBJECTIVE: To identify dietary factors associated with the increase in occurrence of calcium oxalate (CaOx) uroliths and the decrease in occurrence of magnesium ammonium phosphate (MAP) uroliths in cats. DESIGN: Case-control study. ANIMALS: 173 cats with CaOx uroliths, 290 cats with MAP uroliths, and 827 cats without any urinary tract diseases. PROCEDURE: Univariate and multivariate logistic regression were performed. RESULTS: Cats fed diets low in sodium or potassium or formulated to maximize urine acidity had an increased risk of developing CaOx uroliths but a decreased risk of developing MAP uroliths. Additionally, compared with the lowest contents, diets with the highest moisture or protein contents and with moderate magnesium, phosphorus, or calcium contents were associated with decreased risk of CaOx urolith formation. In contrast, diets with moderate fat or carbohydrate contents were associated with increased risk of CaOx urolith formation. Diets with the highest magnesium, phosphorus, calcium, chloride, or fiber contents and moderate protein content were associated with increased risk of MAP urolith formation. On the other hand, diets with the highest fat content were associated with decreased risk of MAP urolith formation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that diets formulated to contain higher protein, sodium, potassium, moisture, calcium, phosphorus, and magnesium contents and with decreased urine acidifying potential may minimize formation of CaOx uroliths in cats. Diets formulated to contain higher fat content and lower protein and potassium contents and with increased urine acidifying potential may minimize formation of MAP uroliths.

Effects of dietary fat and L-carnitine on plasma and whole blood taurine concentrations and cardiac function in healthy dogs fed protein-restricted diets.

OBJECTIVE: To evaluate plasma taurine concentrations (PTC), whole blood taurine concentrations (WBTC), and echocardiographic findings in dogs fed 1 of 3 protein-restricted diets that varied in fat and L-carnitine content. ANIMALS: 17 healthy Beagles. DESIGN: Baseline PTC and WBTC were determined, and echocardiography was performed in all dogs consuming a maintenance diet. Dogs were then fed 1 of 3 protein-restricted diets for 48 months: a low-fat (LF) diet, a high-fat and L-carnitine supplemented (HF + C) diet, or a high-fat (HF) diet. All diets contained methionine and cystine concentrations at or above recommended Association of American Feed Control Officials (AAFCO) minimum requirements. Echocardiographic findings, PTC, and WBTC were evaluated every 6 months. RESULTS: The PTC and WBTC were not significantly different among the 3 groups after 12 months. All groups had significant decreases in WBTC from baseline concentrations, and the HF group also had a significant decrease in PTC. One dog with PT and WBT deficiency developed dilated cardiomyopathy (DCM). Taurine supplementation resulted in significant improvement in cardiac function. Another dog with decreased WBTC developed changes compatible with early DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed that dogs fed protein-restricted diets can develop decreased taurine concentrations; therefore, protein-restricted diets should be supplemented with taurine. Dietary methionine and cystine concentrations at or above AAFCO recommended minimum requirements did not prevent decreased taurine concentrations. The possibility exists that AAFCO recommended minimum requirements are not adequate for dogs consuming protein-restricted diets. Our results also revealed that, similar to cats, dogs can develop DCM secondary to taurine deficiency, and taurine supplementation can result in substantial improvement in cardiac function.

Connections of the nucleus incertus.

The nucleus incertus (NI) is a distinct cell group in caudoventral regions of the pontine periventricular gray, adjacent to the ventromedial border of the caudal dorsal tegmental nucleus. Recent interest in the NI stems from evidence that it represents one of the periventricular sites with the highest expression levels of mRNA encoding the type 1 corticotropin-releasing hormone (CRH) receptor, which has a high affinity for naturally occurring CRH, perhaps accounting for some of the extrapituitary actions of the peptide on autonomic and behavioral components of the stress response. However, almost nothing is known about NI function and hodological relationships. In this paper, we present the results of a systematic analysis of NI inputs and outputs using cholera toxin B subunit as a retrograde tracer and Phaseolus vulgaris-leucoagglutinin as an anterograde tracer. Our retrograde tracer experiments indicate that the NI is in a strategic position to integrate information related to behavioral planning (from the prefrontal cortex), lateral habenular processing, hippocampal function, and oculomotor control. Based on its efferent connections, the NI is in a position to exert significant modulating influences on prefrontal and hippocampal cortical activity, and the nucleus is also in a position to influence brain sites known to control locomotor behavior, attentive states, and learning processes. Overall, the present results support the idea that the NI is a distinct region of the pontine periventricular gray, and together with the superior central (median raphé) and interpeduncular nuclei the NI appears to form a midline behavior control network of the brainstem.

Fluorescence anisotropy: a method for early detection of Alzheimer beta-peptide (Abeta) aggregation.

Time-resolved anisotropy measurements (TRAMS) have been used to study the aggregation of the beta-amyloid (Abeta) peptide which is suspected of playing a central role in the pathogenesis of Alzheimer's Disease (AD). The experiments, which employ small quantities of fluorescently-labelled Abeta, in addition to the untagged peptide, have shown that the sensitive TRAMS technique detects the presence of preformed "seed" particles in freshly prepared solutions of Abeta. More importantly, as 100 microM solutions of Abeta containing tagged Abeta at a concentration level of either 0.5 or 1 microM are incubated, the TRAMS prove capable of detection of the peptide aggregation process through the appearance of a continuously increasing "residual anisotropy" within the time-resolved fluorescence data. The method detects Abeta aggregation in its earliest stages, well before complexation becomes apparent in more conventional methods such as the thioflavin T fluorescence assay. The TRAMS approach promises to provide a most attractive route for establishment of a high-throughput procedure for the early detection of the presence of amyloid aggregates in the screening of biological samples.

Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain.

The organization of axonal projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats. Within the BST, the oval nucleus (BSTov) projects very densely to the fusiform nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal area, rhomboid nucleus, and subcommissural zone. Outside the BST, its heaviest inputs are to the caudal substantia innominata and adjacent central amygdalar nucleus, retrorubral area, and lateral parabrachial nucleus. It generates moderate inputs to the caudal nucleus accumbens, parasubthalamic nucleus, and medial and ventrolateral divisions of the periaqueductal gray, and it sends a light input to the anterior parvicellular part of the hypothalamic paraventricular nucleus and nucleus of the solitary tract. The BSTfu displays a much more complex projection pattern. Within the BST, it densely innervates the anterodorsal area, dorsomedial nucleus, and caudal anterolateral area, and it moderately innervates the BSTov, subcommissural zone, and rhomboid nucleus. Outside the BST, the BSTfu provides dense inputs to the nucleus accumbens, caudal substantia innominata and central amygdalar nucleus, thalamic paraventricular nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic dorsomedial nucleus, perifornical lateral hypothalamic area, and lateral tegmental nucleus. Moderately dense inputs are found in the parastrial, tuberal, dorsal raphé, and parabrachial nuclei and in the retrorubral area, ventrolateral division of the periaqueductal gray, and pontine central gray. Light projections end in the olfactory tubercle, lateral septal nucleus, posterior basolateral amygdalar nucleus, supramammillary nucleus, and nucleus of the solitary tract. These and other results suggest that the BSTov and BSTfu are basal telencephalic parts of a circuit that coordinates autonomic, neuroendocrine, and ingestive behavioral responses during stress.

Modulation of beta-amyloid production and fibrillization.

Alzheimer's disease (AD) is the most common cause of dementia in old age and presently affects an estimated 4 million people in the U.S.A. and 0.75 million people in the U.K. It is a relentless, degenerative brain disease, characterized by progressive cognitive impairment. In the final stages of the disease, patients are often bedridden, doubly incontinent and unable to speak or to recognize close relatives. Pathological changes of Alzheimer's disease include extensive neuronal loss and the presence of numerous neurofibrillary tangles and senile plaques in the brain. The senile plaques contain amyloid fibrils derived from a 39-43-amino-acid peptide referred to as beta-amyloid or A beta. The basic theory of the so-called 'amyloid hypothesis' is that the deposition of aggregated forms of A beta in the brain parenchyma triggers a pathological cascade of events that leads to neurofibrillary tangle formation, neuronal loss and the associated dementia [1]. Here we discuss progress towards the identification of inhibitors of A beta production and fibrillization.

On the fine structure of the pes Hippocampi major (with plates XIII-XXIII). 1886.

We have provided a translation of Golgi's original paper on the mammalian hippocampus (first published in 1883 and reprinted numerous times), along with a preface on its historical context. Golgi believed that this part of the cerebral hemisphere showed best the exact relationship between nerve cells and nerve fibers, the most important problem in 19th century neuroscience.

Structure-based design of non-peptide HIV protease inhibitors.

A number of structurally novel P2-ligands have been designed and synthesized. Incorporation of these ligands in the (R)-(hydroxyethyl)sulfonamide isostere provided a series of potent non-peptidyl HIV protease inhibitors.

Evaluation of urinary carnitine and taurine excretion in 5 cystinuric dogs with carnitine and taurine deficiency.

Five client owned dogs with cystinuria were diagnosed with carnitine and taurine deficiency while participating in a clinical trial that used dietary management of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric dogs before enrollment in the clinical diet trial were quantitatively evaluated for carnitine and taurine. These results were compared to those obtained from 18 healthy Beagles. Both groups of dogs were fed the same maintenance diet for a minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour urine collections was the same for cystinuric dogs and healthy Beagles except that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the end of the collection, whereas Beagles were catheterized at baseline, 8 hours, and at the end of the collection. Three of 5 dogs with cystinuria had increased renal excretion of carnitine. None of the cystinuric dogs had increased renal excretion of taurine, but cystinuric dogs excreted significantly less (P < .05) taurine in their urine than the healthy Beagles. Carnitinuria has not been recognized previously in either humans or dogs with cystinuria, and it may be 1 risk factor for developing carnitine deficiency. Cystinuric dogs in this study were not taurinuric; however, cystine is a precursor amino acid for taurine synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine deficiency in dogs. We suggest that dogs with cystinuria be monitored for carnitine and taurine deficiency or supplemented with carnitine and taurine.

Effects of dietary fat and carnitine on urine carnitine excretion in healthy dogs.

Turnover of carnitine in the body is primarily the result of renal excretion, and high-fat (HF) diets have been shown to increase urine carnitine excretion in healthy people. Recently, increased renal excretion of carnitine was observed in dogs diagnosed with cystinuria and carnitine deficiency. Carnitine deficiency has been linked to dilated cardiomyopathy and lipid storage myopathies in dogs and humans, and low-fat (LF) diets have been beneficial in some human patients with carnitine deficiency. In addition, HF, protein-restricted diets are often recommended for management of cystinuria in dogs. However, whether HF diets increase renal carnitine excretion in dogs or whether dogs with carnitine deficiency would benefit from LF diets remains unknown. Therefore, the purpose of this study was to determine the influence of dietary fat and carnitine on renal carnitine excretion in healthy dogs. Results from this study revealed that an HF diet increased urine carnitine excretion in dogs; however, carnitine excretion with the HF diet was not significantly different from that in dogs consuming an LF diet. Nonetheless, these results raise the possibility that increased renal carnitine excretion associated with HF diets could be one risk factor for development of carnitine deficiency in dogs with an underlying disorder in carnitine metabolism, and some dogs with carnitine deficiency may benefit from an LF diet. Another important observation in this study was that renal excretion of carnitine exceeded dietary intake in all diet groups, confirming previous reports that concluded that canine renal tubular cells reabsorb carnitine poorly when compared with those of humans.

Cerebral hemisphere regulation of motivated behavior.

The goals of this article are to suggest a basic wiring diagram for the motor neural network that controls motivated behavior, and to provide a model for the organization of cerebral hemisphere inputs to this network. Cerebral projections mediate voluntary regulation of a behavior control column in the ventromedial upper brainstem that includes (from rostral to caudal) the medial preoptic, anterior hypothalamic, descending paraventricular, ventromedial, and premammillary nuclei, the mammillary body, and finally the substantia nigra and ventral tegmental area. The rostral segment of this column is involved in controlling ingestive (eating and drinking) and social (defensive and reproductive) behaviors, whereas the caudal segment is involved in controlling general exploratory or foraging behaviors (with locomotor and orienting components) that are required for obtaining any particular goal object. Virtually all parts of the cerebral hemispheres contribute to a triple descending projection - with cortical excitatory, striatal inhibitory, and pallidal disinhibitory components - to specific parts of the behavior control column. The functional dynamics of this circuitry remain to be established.