Nanoscopic compartmentalization of membrane protein motion at the axon initial segment

The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development. We analyzed the mobility of lipid-anchored molecules by high-speed single-particle tracking and correlated positions of membrane molecules with the nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in mobility early in AIS development. Membrane protein motion in the AIS plasma membrane is confined to a repetitive pattern of ∼190-nm-spaced segments along the AIS axis as early as day in vitro 4, and this pattern alternates with actin rings. Mathematical modeling shows that diffusion barriers between the segments significantly reduce lateral diffusion along the axon

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Observation of Coulomb-Assisted Dipole-Forbidden Intraexciton Transitions in Semiconductors

We use terahertz pulses to induce resonant transitions between the eigenstates of optically generated exciton populations in a high-quality semiconductor quantum-well sample. Monitoring the excitonic photoluminescence, we observe transient quenching of the $1s$ exciton emission, which we attribute to the terahertz-induced $1s$-to-$2p$ excitation. Simultaneously, a pronounced enhancement of the $2s$-exciton emission is observed, despite the $1s$-to-$2s$ transition being dipole forbidden. A microscopic many-body theory explains the experimental observations as a Coulomb-scattering mixing of the 2$s$ and 2$p$ states, yielding an effective terahertz transition between the 1$s$ and 2$s$ populations.Comment: 5 pages, 3 figure

Relative validity of a web-based food frequency questionnaire for patients with type 1 and type 2 diabetes in Denmark

BACKGROUND: Diet has an important role in the management of diabetes. However, little is known about dietary intake in Danish diabetes patients. A food frequency questionnaire (FFQ) focusing on most relevant nutrients in diabetes including carbohydrates, dietary fibres and simple sugars was developed and validated. OBJECTIVES: To examine the relative validity of nutrients calculated by a web-based food frequency questionnaire for patients with diabetes. DESIGN: The FFQ was validated against a 4-day pre-coded food diary (FD). Intakes of nutrients were calculated. Means of intake were compared and cross-classifications of individuals according to intake were performed. To assess the agreement between the two methods, Pearson and Spearman's correlation coefficients and weighted kappa coefficients were calculated. SUBJECTS: Ninety patients (64 with type 1 diabetes and 26 with type 2 diabetes) accepted to participate in the study. Twenty-six were excluded from the final study population. SETTING: 64 volunteer diabetes patients at the Steno Diabetes Center. RESULTS: Intakes of carbohydrates, simple sugars, dietary fibres and total energy were higher according to the FFQ compared with the FD. However, intakes of nutrients were grossly classified in the same or adjacent quartiles with an average of 82% of the selected nutrients when comparing the two methods. In general, moderate agreement between the two methods was found. CONCLUSION: The FFQ was validated for assessment of a range of nutrients. Comparing the intakes of selected nutrients (carbohydrates, dietary fibres and simple sugars), patients were classified correctly according to low and high intakes. The FFQ is a reliable dietary assessment tool to use in research and evaluation of patient education for patients with diabetes

Neuronal correlates of serial position performance in amnestic mild cognitive impairment.

Objectives: Delayed recall of the first words of a list - the primacy position – is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI). Methods: We investigated serial position performance in 88 subjects with aMCI using a 16-word list (CVLT). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes. Results: After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or delayed recall. Primacy performance during learning was associated with the right inferior and middle temporal gyrus as well as the right inferior parietal cortex and supramerginal gyrus. During delayed recall, primacy performance was related to the bilateral supramarginal gyri. Conclusions: Our findings suggest a reduced primacy effect in aMCI already during learning, contrasting previous findings in normal cognitive aging. This might indicate impaired encoding and consolidation processes at an early stage of episodic memory acquisition. Furthermore, our data indicates that hippocampal volume may not be a relevant determinant of residual primacy performance in the stage of aMCI, which may rather depend on temporal and parietal neocortical networks

Mental health assessments in refugees and asylum seekers

Background Mental health problems resulting from persecution and forced migration are very common among refugees and asylum seekers and evolve into a major public health challenge in hosting societies. Language barriers often prevent timely access to appropriate health care, leading to chronic trajectories and abortive social integration. Tools for multilingual screening and assessment could be of great benefit for this particularly vulnerable population as well as for policy makers. This study aimed at testing the reliability, feasibility and usability of the Multi-Adaptive Psychological Screening Software (MAPSS), a newly developed Audio Computer-Assisted Self- Interview Software (ACASI) for touchscreen devices, for screening purposes in a clinical setting. Methods In a randomized cross-over design including both MAPSS and paper-pencil clinician-administered interviews, 30 treatment-seeking refugees completed clinical measures and a feasibility questionnaire to rate the user interface of MAPSS. Five professionals performed given tasks in MAPSS and completed usability questionnaires for the administration interface. Results Results showed no differences between the two assessment modalities with regard to symptom scores. The findings suggest good feasibility and usability of MAPSS in traumatized refugees. The administration via MAPSS was significantly shorter than the paper-pencil interview. Conclusion MAPSS may be a cost-effective, flexible and valid alternative to interpreter-based psychometric screening and assessment

Vertical stratification of adult mosquitoes (Diptera: Culicidae) within a tropical rainforest in Sabah, Malaysia.

BACKGROUND: Malaria cases caused by Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques, are increasing rapidly in Sabah, Malaysia. One hypothesis is that this increase is associated with changes in land use. A study was carried out to identify the anopheline vectors present in different forest types and to observe the human landing behaviour of mosquitoes. METHODS: Mosquito collections were carried out using human landing catches at ground and canopy levels in the Tawau Division of Sabah. Collections were conducted along an anthropogenic disturbance gradient (primary forest, lightly logged virgin jungle reserve and salvage logged forest) between 18:00 and 22:00 h. RESULTS: Anopheles balabacensis, a vector of P. knowlesi, was the predominant species in all collection areas, accounting for 70 % of the total catch, with a peak landing time of 18:30-20:00 h. Anopheles balabacensis had a preference for landing on humans at ground level compared to the canopy (p < 0.0001). A greater abundance of mosquitoes were landing in the logged forest compared to the primary forest (p < 0.0001). There was no difference between mosquito abundance in the logged forest and lightly logged forest (p = 0.554). A higher evening temperature (p < 0.0001) and rainfall (p < 0.0001) significantly decreased mosquito abundance during collection nights. CONCLUSIONS: This study demonstrates the potential ability of An. balabacensis to transmit P. knowlesi between canopy-dwelling simian hosts and ground-dwelling humans, and that forest disturbance increases the abundance of this disease vector. These results, in combination with regional patterns of land use change, may partly explain the rapid rise in P. knowlesi cases in Sabah. This study provides essential data on anthropophily for the principal vector of P. knowlesi which is important for the planning of vector control strategies