Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases. While conventional magnetic resonance imaging (MRI) is widely used for brain and cerebellar morphologic evaluation, advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics. Volumetry, voxel-based morphometry, diffusion MRI based fiber tractography, resting state and task related functional MRI, perfusion, and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum. In the present review, after providing a brief description of each technique's advantages and limitations, we focus on their application to the study of cerebellar injury in major neurodegenerative diseases, such as multiple sclerosis, Parkinson's and Alzheimer's disease and hereditary ataxia. A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease, followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance

A Determination of the Phase Diagram of Relaxed Langmuir Monolayers of Behenic Acid

Grazing incidence x‐ray scattering (GIXS) and Brewster angle microscopy (BAM) are used to determine the $\pi–T$ phase diagram of Behenic acid monolayers supported on the surface of water (pH=2.0) over the temperature range of 3$^\circ$C to 20.6$^\circ$C. The phase diagram is constructed from measurements taken during isothermal compressions in which the surface pressure relaxed to a stable value at each surface density, and during temperature scans at fixed average surface density. The phase diagram is different than those previously reported for Behenic acid primarily because of the surface pressure relaxation. For temperatures less than 12$^\circ$C the phase diagram exhibits similar phases and topology as the published diagrams, although the location of the phases in the $\pi–T$ plane is different. Temperature scans combined with the isotherms, and the Clausius–Clapeyron relation are used to determine three coexistence lines that meet in a triple point. Changes in entropy across the phase boundaries are determined. Near room temperature (20.6$^\circ$C) only one phase is measured over the range of surface pressure from 0 dynes/cm to the collapse pressure in contrast to reported measurements on monolayers out of equilibrium (i.e., when the surface pressure is not allowed to relax) that exhibit several phases near room temperature at pressures higher than the collapse pressure. Discrepancies are observed between the average area per molecule ($A_T$) and the area per molecule determined from measurements of the unit cell ($A_X$) in the close packed regions of the phase diagram. It is conjectured that the $\pi–A_X$ plane is a better representation of the ordered equilibrium monolayer phases than the $\pi–A_T$ plane. Isotherms plotted in the $\pi–A_X$ plane are used to determine the compressibility of the ordered phases and the nature of the phase transitions.Engineering and Applied Science

Position Sense Deficits at the Lower Limbs in Early Multiple Sclerosis: Clinical and Neural Correlates

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols

A long-term time series of global and diffuse photosynthetically active radiation in the Mediterranean: interannual variability and cloud effects

Abstract. Measurements of global and diffuse photosynthetically active radiation (PAR) have been carried out on the island of Lampedusa, in the central Mediterranean Sea, since 2002. PAR is derived from observations made with multi-filter rotating shadowband radiometers (MFRSRs) by comparison with a freshly calibrated PAR sensor and by relying on the on-site Langley plots. In this way, a long-term calibrated record covering the period 2002–2016 is obtained and is presented in this work. The monthly mean global PAR peaks in June, with about 160 W m−2, while the diffuse PAR reaches 60 W m−2 in spring or summer. The global PAR displays a clear annual cycle with a semi amplitude of about 52 W m−2. The diffuse PAR annual cycle has a semi amplitude of about 12 W m−2. A simple method to retrieve the cloud-free PAR global and diffuse irradiances in days characterized by partly cloudy conditions has been implemented and applied to the dataset. This method allows retrieval of the cloud-free evolution of PAR and calculation of the cloud radiative effect, CRE, for downwelling PAR. The cloud-free monthly mean global PAR reaches 175 W m−2 in summer, while the diffuse PAR peaks at about 40 W m−2. The cloud radiative effect, CRE, on global and diffuse PAR is calculated as the difference between all-sky and cloud-free measurements. The annual average CRE is about −14.7 W m−2 for the global PAR and +8.1 W m−2 for the diffuse PAR. The smallest CRE is observed in July, due to the high cloud-free condition frequency. Maxima (negative for the global, and positive for the diffuse component) occur in March–April and in October, due to the combination of elevated PAR irradiances and high occurrence of cloudy conditions. Summer clouds appear to be characterized by a low frequency of occurrence, low altitude, and low optical thickness, possibly linked to the peculiar marine boundary layer structure. These properties also contribute to produce small radiative effects on PAR in summer. The cloud radiative effect has been deseasonalized to remove the influence of annual irradiance variations. The monthly mean normalized CRE for global PAR can be well represented by a multi-linear regression with respect to monthly cloud fraction, cloud top pressure, and cloud optical thickness, as determined from satellite MODIS observations. The behaviour of the normalized CRE for diffuse PAR can not be satisfactorily described by a simple multi-linear model with respect to the cloud properties, due to its non-linear dependency, in particular on the cloud optical depth. The analysis suggests that about 77 % of the global PAR interannual variability may be ascribed to cloud variability in winter

Saharan dust aerosol over the central Mediterranean Sea: PM₁₀ chemical composition and concentration versus optical columnar measurements

This study aims to determine the mineral contribution to PM₁₀ in the central Mediterranean Sea, based on 7 yr of daily PM₁₀ samplings made on the island of Lampedusa (35.5° N, 12.6° E). <br><br> The chemical composition of the PM₁₀ samples was determined by ion chromatography for the main ions, and, on selected samples, by particle-induced X-ray emission (PIXE) for the total content of crustal markers. Aerosol optical depth measurements were carried out in parallel to the PM₁₀ sampling. <br><br> The average PM₁₀ concentration at Lampedusa over the period June 2004–December 2010 is 31.5 μg m⁻³, with low interannual variability. The annual means are below the EU annual standard for PM₁₀, but 9.9% of the total number of daily data exceeds the daily threshold value established by the European Commission for PM (50 μg m⁻³, European Community, EC/30/1999). <br><br> The Saharan dust contribution to PM₁₀ was derived by calculating the contribution of Al, Si, Fe, Ti, non-sea-salt (nss) Ca, nssNa, and nssK oxides in samples in which PIXE data were available. Cases in which crustal content exceeded the 75th percentile of the crustal oxide content distribution were identified as elevated dust events. Using this threshold, we obtained 175 events. Fifty-five elevated dust events (31.6%) displayed PM₁₀ higher than 50 μg m⁻³, with dust contributing by 33% on average. <br><br> The crustal contribution to PM₁₀ has an annual average value of 5.42 μg m⁻³, and reaches a value as high as 67.9 μg m⁻³ (corresponding to 49% of PM₁₀) during an intense Saharan dust event. <br><br> The crustal content estimated from a single tracer, such as Al or Ca, is in good agreement with the one calculated as the sum of the metal oxides. Conversely, larger crustal contents are derived by applying the EU guidelines for demonstration and subtraction of exceedances in PM₁₀ levels due to high background of natural aerosol. The crustal aerosol amount and contribution to PM₁₀ showed a very small seasonal dependence; conversely, the dust columnar burden displays an evident annual cycle, with a strong summer maximum (monthly average aerosol optical depth at 500 nm up to 0.28 in June–August). We found that 71.3% of the dust events identified from optical properties over the atmospheric column display a high dust content at the ground level. Conversely, the remaining 28.7% of cases present a negligible or small impact on the surface aerosol composition due to the transport processes over the Mediterranean Sea, where dust frequently travels above the marine boundary layer, especially in summer. <br><br> Based on backward trajectories, two regions, one in Algeria–Tunisia, and one in Libya, are identified as main source areas for intense dust episodes occurring mainly in autumn and winter. Data on the bulk composition of mineral aerosol arising from these two source areas are scarce; results on characteristic ratios between elements show somewhat higher values of Ca / Al and (Ca + Mg) / Fe (2.5 ± 1.0, and 4.7 ± 2.0, respectively) for Algeria–Tunisia than for Libyan origin (Ca / Al = 1.9 ± 0.7 and (Ca + Mg) / Fe = 3.3 ± 1.1)

Heat sensitivity of first host and cercariae may restrict parasite transmission in a warming sea

To predict global warming impacts on parasitism, we should describe the thermal tolerance of all players in host–parasite systems. Complex life-cycle parasites such as trematodes are of particular interest since they can drive complex ecological changes. This study evaluates the net response to temperature of the infective larval stage of Himasthla elongata, a parasite inhabiting the southwestern Baltic Sea. The thermal sensitivity of (i) the infected and uninfected first intermediate host (Littorina littorea) and (ii) the cercarial emergence, survival, self-propelling, encystment, and infection capacity to the second intermediate host (Mytilus edulis sensu lato) were examined. We found that infection by the trematode rendered the gastropod more susceptible to elevated temperatures representing warm summer events in the region. At 22 °C, cercarial emergence and infectivity were at their optimum while cercarial survival was shortened, narrowing the time window for successful mussel infection. Faster out-of-host encystment occurred at increasing temperatures. After correcting the cercarial emergence and infectivity for the temperature-specific gastropod survival, we found that warming induces net adverse effects on the trematode transmission to the bivalve host. The findings suggest that gastropod and cercariae mortality, as a tradeoff for the emergence and infectivity, will hamper the possibility for trematodes to flourish in a warming ocean

Direct calibration of PICKY-designed microarrays

Abstract Background Few microarrays have been quantitatively calibrated to identify optimal hybridization conditions because it is difficult to precisely determine the hybridization characteristics of a microarray using biologically variable cDNA samples. Results Using synthesized samples with known concentrations of specific oligonucleotides, a series of microarray experiments was conducted to evaluate microarrays designed by PICKY, an oligo microarray design software tool, and to test a direct microarray calibration method based on the PICKY-predicted, thermodynamically closest nontarget information. The complete set of microarray experiment results is archived in the GEO database with series accession number GSE14717. Additional data files and Perl programs described in this paper can be obtained from the website http://www.complex.iastate.edu under the PICKY Download area. Conclusion PICKY-designed microarray probes are highly reliable over a wide range of hybridization temperatures and sample concentrations. The microarray calibration method reported here allows researchers to experimentally optimize their hybridization conditions. Because this method is straightforward, uses existing microarrays and relatively inexpensive synthesized samples, it can be used by any lab that uses microarrays designed by PICKY. In addition, other microarrays can be reanalyzed by PICKY to obtain the thermodynamically closest nontarget information for calibration

Shared probe design and existing microarray reanalysis using PICKY

<p>Abstract</p> <p>Background</p> <p>Large genomes contain families of highly similar genes that cannot be individually identified by microarray probes. This limitation is due to thermodynamic restrictions and cannot be resolved by any computational method. Since gene annotations are updated more frequently than microarrays, another common issue facing microarray users is that existing microarrays must be routinely reanalyzed to determine probes that are still useful with respect to the updated annotations.</p> <p>Results</p> <p><smcaps>PICKY</smcaps> 2.0 can design shared probes for sets of genes that cannot be individually identified using unique probes. <smcaps>PICKY</smcaps> 2.0 uses novel algorithms to track sharable regions among genes and to strictly distinguish them from other highly similar but nontarget regions during thermodynamic comparisons. Therefore, <smcaps>PICKY</smcaps> does not sacrifice the quality of shared probes when choosing them. The latest <smcaps>PICKY</smcaps> 2.1 includes the new capability to reanalyze existing microarray probes against updated gene sets to determine probes that are still valid to use. In addition, more precise nonlinear salt effect estimates and other improvements are added, making <smcaps>PICKY</smcaps> 2.1 more versatile to microarray users.</p> <p>Conclusions</p> <p>Shared probes allow expressed gene family members to be detected; this capability is generally more desirable than not knowing anything about these genes. Shared probes also enable the design of cross-genome microarrays, which facilitate multiple species identification in environmental samples. The new nonlinear salt effect calculation significantly increases the precision of probes at a lower buffer salt concentration, and the probe reanalysis function improves existing microarray result interpretations.</p