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

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

Renal accumulation of prooxidant mineral elements and CKD in domestic cats

Felids have a high incidence of chronic kidney disease (CKD), for which the most common renal lesion is chronic interstitial nephritis (CIN). CIN can be induced by tissue oxidative stress, which is determined by the cellular balance of pro- and anti-oxidant metabolites. Fish-flavoured foods are more often fed to cats than dogs, and such foods tend to have higher arsenic content. Arsenic is a pro-oxidant metallic element. We propose that renal accumulation of pro-oxidant elements such as arsenic and depletion of anti-oxidant elements such as zinc, underpin the high incidence of CIN in domestic cats. Total arsenic and other redox-reactive metal elements were measured in kidneys (after acid-digestion) and urine (both by inductively-coupled plasma-mass spectrometry) of domestic cats (kidneys, n = 56; urine, n = 21), domestic dogs (kidneys, n = 54; urine, n = 28) and non-domesticated Scottish Wildcats (kidneys, n = 17). Renal lesions were graded by severity of CIN. In our randomly sampled population, CIN was more prevalent in domestic cat versus domestic dog (51%, n = 32 of 62 cats; 15%, 11 of 70 dogs were positive for CIN, respectively). CIN was absent from all Scottish wildcats. Tissue and urinary (corrected for creatinine) arsenic content was higher in domestic cats, relative to domestic dogs and wildcats. Urine arsenic was higher in domestic cats and dogs with CIN. Arsenobetaine, an organic and relatively harmless species of arsenic, was the primary form of arsenic found in pet foods. In summary, the kidneys of domestic cats appear to have greater levels of pro-oxidant trace elements, as compared to dogs and wildcats. Since there was no difference in renal arsenic levels in cats with or without CIN, renal arsenic accumulation does not appear a primary driver of excess CIN in cats. Given clear differences in renal handling of pro vs. anti-oxidant minerals between cats and dogs, further in vivo balance studies are warranted. These may then inform species-specific guidelines for trace element incorporation into commercial diets

Recognition of Famous Names Predicts Cognitive Decline in Healthy Elders

Objective: The ability to recognize familiar people is impaired in both Mild Cognitive Impairment (MCI) and Alzheimer’s Dementia (AD). In addition, both groups often demonstrate a time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently. In this study, we examined the TG in cognitively intact elders for remote famous names (1950–1965) compared to more recent famous names (1995–2005). We hypothesized that the TG pattern on a famous name recognition task (FNRT) would predict future cognitive decline, and also show a significant correlation with hippocampal volume. Method: Seventy-eight healthy elders (ages 65–90) with age-appropriate cognitive functioning at baseline were administered a FNRT. Follow-up testing 18 months later produced two groups: Declining (≥ 1 SD reduction on at least one of three measures) and Stable (\u3c 1 SD). Results: The Declining group (N = 27) recognized fewer recent famous names than the Stable group (N = 51), although recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampi were significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining vs. Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: The TG for famous name recognition may serve as an early preclinical cognitive marker of cognitive decline in healthy older individual

Imaging single cells in a beam of live cyanobacteria with an X-ray laser

Citation: van der Schot, G., Svenda, M., Maia, F., Hantke, M., DePonte, D. P., Seibert, M. M., . . . Ekeberg, T. (2015). Imaging single cells in a beam of live cyanobacteria with an X-ray laser. Nature Communications, 6, 9. doi:10.1038/ncomms6704There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from individual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential.Additional Authors: Almeida, N. F.;Odic, D.;Hasse, D.;Carlsson, G. H.;Larsson, D. S. D.;Barty, A.;Martin, A. V.;Schorb, S.;Bostedt, C.;Bozek, J. D.;Rolles, D.;Rudenko, A.;Epp, S.;Foucar, L.;Rudek, B.;Hartmann, R.;Kimmel, N.;Holl, P.;Englert, L.;Loh, N. T. D.;Chapman, H. N.;Andersson, I.;Hajdu, J.;Ekeberg, T

A statistical approach to detect protein complexes at X-ray free electron laser facilities

The Flash X-ray Imaging (FXI) technique, under development at X-ray free electron lasers (XFEL), aims to achieve structure determination based on diffraction from individual macromolecular complexes. We report an FXI study on the first protein complex-RNA polymerase II-ever injected at an XFEL. A successful 3D reconstruction requires a high number of observations of the sample in various orientations. The measured diffraction signal for many shots can be comparable to background. Here we present a robust and highly sensitive hit-identification method based on automated modeling of beamline background through photon statistics. It can operate at controlled false positive hit-rate of 3 x10(-5). We demonstrate its power in determining particle hits and validate our findings against an independent hit-identification approach based on ion time-of-flight spectra. We also validate the advantages of our method over simpler hit-identification schemes via tests on other samples and using computer simulations, showing a doubled hit-identification power

Fur in Magnetospirillum gryphiswaldense Influences Magnetosomes Formation and Directly Regulates the Genes Involved in Iron and Oxygen Metabolism

Magnetospirillum gryphiswaldense strain MSR-1 has the unique capability of taking up large amounts of iron and synthesizing magnetosomes (intracellular magnetic particles composed of Fe3O4). The unusual high iron content of MSR-1 makes it a useful model for studying biological mechanisms of iron uptake and homeostasis. The ferric uptake regulator (Fur) protein plays a key role in maintaining iron homeostasis in many bacteria. We identified and characterized a fur-homologous gene (MGR_1314) in MSR-1. MGR_1314 was able to complement a fur mutant of E. coli in iron-responsive manner in vivo. We constructed a fur mutant strain of MSR-1. In comparison to wild-type MSR-1, the mutant strain had lower magnetosome formation, and was more sensitive to hydrogen peroxide and streptonigrin, indicating higher intracellular free iron content. Quantitative real-time RT-PCR and chromatin immunoprecipitation analyses indicated that Fur protein directly regulates expression of several key genes involved in iron transport and oxygen metabolism, in addition it also functions in magnetosome formation in M. gryphiswaldense

Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser

Citation: Ekeberg, T., Svenda, M., Abergel, C., Maia, F., Seltzer, V., Claverie, J. M., . . . Hajdu, J. (2015). Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser. Physical Review Letters, 114(9), 6. doi:10.1103/PhysRevLett.114.098102We present a proof-of-concept three-dimensional reconstruction of the giant mimivirus particle from experimentally measured diffraction patterns from an x-ray free-electron laser. Three-dimensional imaging requires the assembly of many two-dimensional patterns into an internally consistent Fourier volume. Since each particle is randomly oriented when exposed to the x-ray pulse, relative orientations have to be retrieved from the diffraction data alone. We achieve this with a modified version of the expand, maximize and compress algorithm and validate our result using new methods.Additional Authors: Andersson, I.;Loh, N. D.;Martin, A. V.;Chapman, H.;Bostedt, C.;Bozek, J. D.;Ferguson, K. R.;Krzywinski, J.;Epp, S. W.;Rolles, D.;Rudenko, A.;Hartmann, R.;Kimmel, N.;Hajdu, J