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Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
Moringa oleifera is a rich source of antioxidants and a promising feed for livestock, due to significant amounts of protein, vitamins, carotenoids and polyphenols, and negligible amounts of anti-nutritional factors. The current study tested whether ensiling would preserve the antioxidant capacity of M. oleifera plants, and assessed whether Moringa silage, fed as a substitute for maize silage, would confer health-promoting traits and affect milk production in dairy cows. To this end, hand-harvested M. oleifera plants were ensiled, with or without molasses and inoculants, in anaerobic jars at room temperature (25 °C) for 37 days. At the end of the storage period the silages were analysed for pH, lactic acid and acetic acid concentrations, aerobic stability, antioxidant capacity, polyphenols and protein content, and tocopherols and carotenoids concentrations. Moringa silages exhibited higher antioxidant capacity compared with fresh and dried Moringa plants, not related to polyphenol content but presumably attributed to accumulation of amino acids and low molecular weight peptides. Based on these findings, a large-scale ensiling protocol was implemented, followed by a feeding trial for dairy cows, in which Moringa silage replaced 263 g maize silage/kg in the diet. Cows fed Moringa silage had higher milk yield and antioxidant capacity and lower milk somatic cell counts compared with controls, during some stages of lactation. These findings imply that ensiling M. oleifera is an appropriate practice by which health and production of dairy cows can be improved.
Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals. (JINS, 2013, 19, 1–9)
Recent studies have claimed the existence of very massive stars (VMS) up to 300 M⊙ in the local Universe. As this finding may represent a paradigm shift for the canonical stellar upper-mass limit of 150 M⊙, it is timely to discuss the status of the data, as well as the far-reaching implications of such objects. We held a Joint Discussion at the General Assembly in Beijing to discuss (i) the determination of the current masses of the most massive stars, (ii) the formation of VMS, (iii) their mass loss, and (iv) their evolution and final fate. The prime aim was to reach broad consensus between observers and theorists on how to identify and quantify the dominant physical processes.
On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1–11)
Gas-filled Time Projection Chambers (TPCs) with Gas Electron Multipliers (GEMs) and pixels appear suitable for direction-sensitive WIMP dark matter searches. We present the background and motivation for our work on this technology, past and ongoing prototype work, and a development path towards an affordable, 1-m3-scale directional dark matter detector, D3. Such a detector may be particularly suitable for low-mass WIMP searches, and perhaps sufficiently sensitive to clearly determine whether the signals seen by DAMA, CoGeNT, and CRESST-II are due to low-mass WIMPs or background.
This investigation examined the relation between developmental trajectories jointly estimated for social and physical aggression and adjustment problems at age 14. Teachers provided ratings of children's social and physical aggression in Grades 3, 4, 5, 6, and 7 for a sample of 255 children (131 girls, 21% African American, 52% European American, 21% Mexican American). Participants, parents, and teachers completed measures of the adolescent's adjustment to assess internalizing symptoms, rule-breaking behaviors, and borderline and narcissistic personality features. Results showed that membership in a high and rising trajectory group predicted rule-breaking behaviors and borderline personality features. Membership in a high desister group predicted internalizing symptoms, rule-breaking behaviors, and borderline and narcissistic personality features. The findings suggest that although low levels of social and physical aggression may not bode poorly for adjustment, individuals engaging in high levels of social and physical aggression in middle childhood may be at greatest risk for adolescent psychopathology, whether they increase or desist in their aggression through early adolescence.
We recently demonstrated that C60 and C70, as well as other fullerenes, can be deposited and accumulated on surfaces using laser ablation of graphite in an Inert gas atmosphere. After learning of the work of Krätschmer et al. indicating the presence of C60 in carbon soot, we showed that samples consisting almost exclusively of C60 and C70 can be sublimed from such soot. Vibrational Raman spectra of C60 and C70 were obtained from these samples. The C60 spectrum Is consistent with the calculated spectrum of Buckmlnsterfullerene, and the strongest three lines can be assigned on the basis of frequency and polarization. The NMR spectrum of dissolved C60 was then obtained, and found to consist of a single resonance, establishing the icosahedral symmetry of this molecule. STM images of the C60 molecules on a Au(111) crystal face show that these clusters form hexagonal arrays with an intercluster spacing of 11.0 Å and are mobile at ambient temperature. Distinctly taller species evident in the arrays are believed to be C70 clusters. Vibrational Raman and infrared spectra have also been obtained for separated C60 and C70.
Computer simulations of the collision cascade process were used to investigate surface densification during ion beam assisted deposition (IBAD). The objective of the investigation was to see if densification resulted directly from the cascade, without any contribution from diffusion enhancement brought on by the bombardment. Calculations, using the computer code MARLOWE, were carried out for Ar bombardment of a crystalline Ge target, containing a void, using ion beam energies of 0.065, 0.5 and 1 keV. These results were used as data for a differential equation that describes the effect on void size of the simultaneous Ge atom deposition and Ar ion bombardment of a substrate containing voids. The present attempt examined the effects of irradiations on voids of 17 and 35 vacancies.
This study hypothesized that ginger (Zingiber officinale) and cranberry (Vaccinium macrocarpon) extracts would alter the physiological response to exercise as well as markers of muscle damage, and mRNA expression for the inflammatory cytokines tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-6 (IL-6) after an exhaustive bout of exercise in horses. Nine unfit Standardbred mares (age 10 ± 4 years, ~450 kg) completed three graded exercise tests (GXTs) in a crossover design, where they were assigned to the initial order of treatment in a randomized fashion. The GXTs were conducted between 07.00 and 12.00 hours, 7 days apart. Mares received either water (2 l), cranberry (~30 g in 2 l of water) or ginger (~30 g in 2 l of water) extract 1 h prior to testing. Blood samples were taken prior to dosing (pre-exercise), at the end of each step of the GXT, at the end of the exercise and at 2, 5 and 30 min, 1, 2, 4 and 24 h post-GXT. Plasma total protein (TP) concentration and haematocrit (HCT) were analysed immediately following the tests. Analysis of creatine kinase (CK) and aspartate aminotransferase (AST) was done commercially. There was no effect of treatment (P>0.05) on VO2max, run-time to fatigue, core temperature, TP or HCT. CK was substantially elevated (P < 0.05) in the ginger group at 4 h post-GXT. All CK levels returned to baseline 24 h post-GXT. No change (P>0.05) was noted in AST. A slight increase (P < 0.05) in CK was seen in all groups at 2 h post-GXT. The cranberry group had significantly lower TNF-α mRNA expression than the control and ginger groups. Ginger appeared to influence (P < 0.05) the upregulation and expression of IFN-γ mRNA at 30 min post-GXT, but, more strikingly, significantly decreased recovery time defined as the time for VO2 to recover from the peak observed at fatigue to a post-exercise plateau (ginger = 101 ± 3 s, water = 130 ± 14 s, cranberry = 131 ± 16 s). No effect of treatment or exercise (P>0.05) was seen on IL-6 mRNA expression. Results suggest that cranberry extract blunts the upregulation and expression of TNF-α mRNA, while ginger extract reduces cardiovascular recovery time in horses completing a short, exhaustive bout of exercise.
Good cognitive performance requires adherence to rules specific to the task at hand. Patients with neurological disease often make rule violation (RV) errors, but the anatomical basis for RV during cognitive testing remains debated. The present study examined the neuroanatomical correlates of RV errors made on tests of executive functioning in 166 subjects diagnosed with neurodegenerative disease or as neurologically healthy. Specifically, RV errors were voxel-wisely correlated with gray matter volume derived from high-definition magnetic resonance images using voxel-based morphometry implemented in SPM2. Latent variable analysis showed that RV errors tapped a unitary construct separate from repetition errors. This analysis was used to generate factor scores to represent what is common among RV errors across tests. The extracted RV factor scores correlated with tissue loss in the lateral middle and inferior frontal gyri and the caudate nucleus bilaterally. When a more stringent control for global cognitive functioning was applied using Mini Mental State Exam scores, only the correlations with the right lateral prefrontal cortex (PFC) remained significant. These data underscore the importance of right lateral PFC in behavioral monitoring and highlight the potential of RV error assessment for identifying patients with damage to this region. (JINS, 2009, 15, 354–364.)
The purpose of this study was to examine the relationships between
lobar volumes and set shifting. We studied 101 subjects, including 36
normal controls, 16 patients with probable Alzheimer's disease, 30
patients with frontotemporal dementia (FTD), and 19 patients with semantic
dementia (SD), using a shifting paradigm that carefully controlled for
component abilities. Subjects were administered two conditions of the
Delis–Kaplan Executive Function System (D-KEFS) Design Fluency Test.
In the control condition (DF:Control), examinees generated as many unique
designs as possible in 60 s by drawing lines connecting only unfilled
dots. In the switching condition (DF:Switch), examinees generated designs
by drawing lines alternating between filled and unfilled dots. We used
BRAINS2 software to generate volumes of the right and left frontal,
temporal, and parietal lobes. Partial correlations and multiple
regressions showed that, after controlling for Mini-Mental State
Examination and DF:Control, only the right and left frontal lobe volumes
significantly correlated with the DF:Switch, most clearly in the FTD and
SD groups. Follow-up analyses indicated that frontal contributions to
shifting were not related to working memory. Results highlight the
importance of carefully controlling for component cognitive processes when
studying executive functioning. (JINS, 2007, 13,
This study tested the hypothesis that the hippocampus has a
relatively specific role in retaining information over delays.
Thirty-seven subjects with probable Alzheimer's disease were
evaluated with a verbal memory task and structural MRI. Cortical gray
matter but not hippocampal volume predicted immediate free recall. In
contrast, hippocampal volume was the best predictor of how well
information was retained over a delay, even after controlling for
levels of immediate recall. Results suggest that the role of the
hippocampus is relatively specific to the consolidation of new
memories. (JINS, 2004, 10, 639–643.)
In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.