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

Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas