Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer\u27s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD

LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells

Melanoma cells steer out of tumours using self-generated lysophosphatidic acid (LPA) gradients. The cells break down LPA, which is present at high levels around the tumours, creating a dynamic gradient that is low in the tumour and high outside. They then also migrate up this gradient, creating a complex and evolving outward chemotactic stimulus. Here we introduce a new assay for self-generated chemotaxis, and show that raising LPA levels causes a delay in migration rather than loss of chemotactic efficiency. Knockdown of the lipid phosphatase LPP3 - but not its homologues LPP1 or LPP2 - diminishes the cell's ability to break down LPA. This is specific for chemotactically active LPAs, such as the 18:1 and 20:4 species. Inhibition of autotaxin-mediated LPA production does not diminish outward chemotaxis, but loss of LPP3-mediated LPA breakdown blocks it. Similarly, in both 2D and 3D invasion assays, knockdown of LPP3 diminishes melanoma cells' ability to invade. Our results demonstrate that LPP3 is the key enzyme in melanoma cells' breakdown of LPA, and confirm the importance of attractant breakdown in LPA-mediated cell steering

Dynamic Responses of Calving Caribou to Oilfields in Northern Alaska

Past research has suggested that during the calving period, caribou (Rangifer tarandus) in Arctic Alaska generally avoid areas within 1 km of oilfield roads with traffic. However, avoidance is not absolute, and caribou may habituate to infrastructure (e.g., buildings, roads, well pads) and human activity. We conducted road-based surveys of caribou in oilfields on Alaska’s Arctic Coastal Plain during the late calving and post-calving periods of June in 2000–02. We recorded location, composition, and behavior of caribou groups located less than 1 km from active gravel roads and production pads. Caribou groups with calves were on average distributed farther from oilfield infrastructure than were groups without calves, but habituation to oilfield activities, indicated by decreased avoidance, occurred at similar rates for groups with and without calves. During the calving period, sighting rates were greater in areas of low human activity, and calf percentages tended to be greater at night when oilfield activity was reduced. Caribou groups were on average closer to infrastructure during the post-calving periods than during the calving periods in 2000 and 2001, but not in 2002. In 2002, when snow melted early, caribou groups were closer to infrastructure during the calving period than in 2000 and 2001, when snow melted later, emphasizing the importance of examining environmental variables when investigating the dynamic interactions of caribou and oilfields. Overall, caribou appeared to habituate to active oilfield infrastructure after the calving period in 2000, late in the calving period in 2001, and likely before our sampling period in 2002. The timing of annual rehabituation was positively correlated with timing of spring snowmelt. Land and wildlife managers can use information from this study to develop calving period-specific mitigation measures that are more effective and flexible.Selon des recherches antérieures, pendant sa période de vêlage, le caribou (Rangifer tarandus) de l’Alaska arctique évite généralement les régions se trouvant à l’intérieur d’un kilomètre des routes où circulent des véhicules menant aux chantiers pétroliers. Cependant, cet évitement n’est pas absolu, et le caribou peut s’accoutumer aux infrastructures (comme les bâtiments, les routes et les chantiers) et à l’activité humaine. Nous avons effectué le dénombrement des caribous près des routes des champs de pétrole de la plaine côtière arctique de l’Alaska vers la fin de la période de vêlage et après la période de vêlage de juin 2000 à 2002. Nous avons consigné l’emplacement, la composition et le comportement des groupes de caribous se trouvant à moins d’un kilomètre des routes de gravier et des chantiers de production en activité. En moyenne, les caribous qui avaient des petits se tenaient plus loin des infrastructures pétrolières que les groupes de caribous qui n’avaient pas de petits. Cela dit, l’accoutumance aux activités pétrolières, dénotée par un moins grand évitement, survenait à des taux semblables pour les groupes qui avaient des petits et les groupes qui n’en avaient pas. Pendant la période de vêlage, les taux d’observation de caribous étaient plus élevés dans les régions où il y avait peu d’activité humaine, et les pourcentages de petits avaient tendance à être plus élevés la nuit, lorsqu’il y avait peu de va-et-vient aux chantiers. En moyenne, les groupes de caribous s’approchaient plus des infrastructures pendant les périodes suivant le vêlage des années 2000 et 2001, mais pas en 2002. En 2002, quand la neige a fondu plus tôt que d’habitude, les groupes de caribous s’approchaient plus des infrastructures pendant la période de vêlage qu’en 2000 et 2001, lorsque la neige a fondu plus tard. Cela fait ressortir l’importance de tenir compte des variables environnementales lorsque nous faisons des enquêtes sur les interactions dynamiques entre les caribous et les champs de pétrole. Dans l’ensemble, les caribous semblaient s’accoutumer aux infrastructures pétrolières en activité après la période de vêlage en 2000, puis vers la fin de la période de vêlage en 2001, et vraisemblablement avant notre période d’échantillonnage en 2002. Le moment de l’accoutumance annuelle coïncidait positivement avec le moment de la fonte des neiges au printemps. Les gestionnaires des terres et de la faune peuvent se servir de l’information émanant de cette étude pour élaborer des mesures d’atténuation tenant compte de la période de vêlage, mesures qui sont plus efficaces et qui présentent plus de souplesse

Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI

Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment

Background: Exercise training has been associated with greater cerebral blood flow (CBF) in cognitively normal older adults (CN). Alterations in CBF, including compensatory perfusion in the prefrontal cortex, may facilitate changes to the brain’s neural infrastructure. Objective: To examine the effects of a 12-week aerobic exercise intervention on resting CBF and cognition in CN and those with mild cognitive impairment (MCI). We hypothesized individuals with MCI (vs. CN) would exhibit greater whole brain CBF at baseline and that exercise would mitigate these differences. We also expected CBF changes to parallel cognitive improvements. Methods: Before and after a 12-week exercise intervention, 18 CN and 17 MCI participants (aged 61–88) underwent aerobic fitness testing, neuropsychological assessment, and an MRI scan. Perfusion-weighted images were collected using a GE 3T MR system. Repeated measures analyses of covariance were used to test within- and between-group differences over time, followed by post-hoc analyses to examine links between CBF changes and cognitive improvement. Results: At baseline, individuals with MCI (vs. CN) exhibited significantly elevated perfusion in the left insula. Twelve weeks of aerobic exercise reversed this discrepancy. Additionally, exercise improved working memory (measured by the Rey Auditory Verbal Learning Test) and verbal fluency (measured by the Controlled Oral Word Association Test) and differentially altered CBF depending on cognitive status. Among those with MCI, decreased CBF in the left insula and anterior cingulate cortex was associated with improved verbal fluency. Conclusions: Exercise training alters CBF and improves cognitive performance in older adults with and without cognitive impairment. Future studies must evaluate the mediating effects of CBF on the association between exercise training and cognition

The Sensitivity and Psychometric Properties of a Brief Computer-Based Cognitive Screening Battery in a Depression Clinic

At present, there is poor accuracy in assessing cognitive and vegetative symptoms in depression using clinician or self-rated measures, suggesting the need for development of standardized tasks to assess these functions. The current study assessed the psychometric properties and diagnostic specificity of a brief neuropsychological screening battery designed to assess core signs of depression; psychomotor retardation, attention and executive functioning difficulties, and impaired emotion perception within an outpatient psychiatry setting. Three hundred eighty-four patients with mood disorders and 77 healthy volunteers participated. A large percentage of patients met diagnostic criteria for Major Depressive Disorder alone (49%) or with another comorbid psychiatric disorder (24%). A brief, 25-min battery of computer-based tests was administered to control participants and patients measuring the constructs of inhibitory control, attention, visual perception, and both executive and visual processing speed. The patient groups performed significantly worse than the control group regardless of diagnosis on visual perception and attention accuracy and processing speed factors. Surprisingly, the anxiety disorder group performed better than several other psychiatric disorder groups in inhibitory control accuracy. Developing valid and reliable measures of cognitive signs in mood disorders creates excellent opportunities for tracking cognitive status prior to initiation of treatment, and allows for reliable retest following treatment

SLIM Ultrahigh Resolution Ion Mobility Spectrometry Separations of Isotopologues and Isotopomers Reveal Mobility Shifts due to Mass Distribution Changes

We report on separations of ion isotopologues and isotopomers using ultrahigh-resolution traveling wave-based Structures for Lossless Ion Manipulations with serpentine ultralong path and extended routing ion mobility spectrometry coupled to mass spectrometry (SLIM SUPER IMS-MS). Mobility separations of ions from the naturally occurring ion isotopic envelopes (e.g., [M], [M+1], [M+2], ... ions) showed the first and second isotopic peaks (i.e., [M+1] and [M+2]) for various tetraalkylammonium ions could be resolved from their respective monoisotopic ion peak ([M]) after SLIM SUPER IMS with resolving powers of ∼400–600. Similar separations were obtained for other compounds (e.g., tetrapeptide ions). Greater separation was obtained using argon versus helium drift gas, as expected from the greater reduced mass contribution to ion mobility described by the Mason–Schamp relationship. To more directly explore the role of isotopic substitutions, we studied a mixture of specific isotopically substituted (15N, 13C, and 2H) protonated arginine isotopologues. While the separations in nitrogen were primarily due to their reduced mass differences, similar to the naturally occurring isotopologues, their separations in helium, where higher resolving powers could also be achieved, revealed distinct additional relative mobility shifts. These shifts appeared correlated, after correction for the reduced mass contribution, with changes in the ion center of mass due to the different locations of heavy atom substitutions. The origin of these apparent mass distribution-induced mobility shifts was then further explored using a mixture of Iodoacetyl Tandem Mass Tag (iodoTMT) isotopomers (i.e., each having the same exact mass, but with different isotopic substitution sites). Again, the observed mobility shifts appeared correlated with changes in the ion center of mass leading to multiple monoisotopic mobilities being observed for some isotopomers (up to a ∼0.04% difference in mobility). These mobility shifts thus appear to reflect details of the ion structure, derived from the changes due to ion rotation impacting collision frequency or momentum transfer, and highlight the potential for new approaches for ion structural characterization

To Sleep, to Strive, or Both: How Best to Optimize Memory

While numerous studies have shown that a night of sleep profits memory relative to wake, we still have little understanding about what factors mediate this effect of sleep. A clear understanding of the dynamics of this effect of sleep beyond the initial night of sleep is also lacking. Here, we examined the effect of extrinsic rewards on sleep-dependent declarative memory processing across 12 and 24 hr training-retest intervals. Subjects were either paid based on their performance at retest ($1 for each correct answer), or received a flat fee for participation. After a 12 hr interval we observed pronounced benefits of both sleep and reward on memory. Over an extended 24 hr interval we found 1) that an initial night of sleep partially protects memories from subsequent deterioration during wake, and 2) that sleep blocks further deterioration, and may even have a restorative effect on memory, when it follows a full day of wake. Interestingly, the benefit imparted to rewarded (relative to unrewarded) stimuli was equal for sleep and wake subjects, suggesting that the sleeping brain may not differentially process rewarded information, relative to wake. However, looking at the overall impact of sleep relative to reward in this protocol, it was apparent that sleep both imparted a stronger mnemonic boost than reward, and provided a benefit to memory regardless of whether it occurred in the first or the second 12 hrs following task training

Comparison of a Flow Assay for Brucellosis Antibodies with the Reference cELISA Test in West African Bos indicus

Brucellosis is considered by the Food and Agricultural Organisation and the World Health Organisation as one of the most widespread zoonoses in the world. It is a major veterinary public health challenge as animals are almost exclusively the source of infection for people. It is often undiagnosed in both human patients and the animal sources and it is widely acknowledged that the epidemiology of brucellosis in humans and animals is poorly understood, particularly in sub-Saharan Africa. It is therefore important to develop better diagnostic tools in order to improve our understanding of the epidemiology and also for use in the field for disease control and eradication. As with any new diagnostic test, it is essential that it is validated in as many populations as possible in order to characterise its performance and improve the interpretation of its results. This paper describes a comparison between a new lateral flow assasy (LFA) for bovine brucellosis and the widely used cELISA in a no gold standard analysis to estimate test performance in this West African cattle population. A Bayesian formulation of the Hui-Walter latent class model incorporated previous studies' data on sensitivity and specificity of the cELISA. The results indicate that the new LFA is very sensitive (∼87%) and highly specific (∼97%). The analysis also suggests that the current cut-off of the cELSIA may not be optimal for this cattle population but alternative cut-offs did not significantly change the estimates of the LFA. This study demonstrates the potential usefulness of this simple to use test in field based surveillance and control which could be easily adopted for use in developing countries with only basic laboratory facilities