Automated, high accuracy classification of Parkinsonian disorders: a pattern recognition approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process

Komarekiella atlantica gen. et sp. nov. (Nostocaceae, Cyanobacteria): a new subaerial taxon from the Atlantic Rainforest and Kauai, Hawaii

Six strains of Cyanobacteria sampled in the Brazilian Atlantic rainforest and one strain from Kauai, Hawaii, were studied using morphological and molecular approaches, including 16S rRNA gene phylogenies and 16S–23S ITS secondary structures, and are herein described as Komarekilla atlantica gen. et sp. nov.. Morphologically they are similar to Nostoc, Desmonostoc, Halotia, and Mojavia and indistinguishable from Chlorogloeopsis. The parsimony and Bayesian phylogenies of the 16S rDNA show that these strains are close to nostocacean strains, in strongly supported clades and separated from all other genera. The secondary structures of the 16S–23S ITS were very consistent between strains of K. atlantica, but distinctly different from structures in other close taxa. Of special note, the Hawaiian strain of K. atlantica had 16S sequence identities of 99.5– 100% to the Brazilian strains, and 16S–23S ITS sequence identities of 99.4–99.8% to the Brazilian strains, and consequently likely represents a very recent introduction of the species to Kauai from South America, the geographic source of many of the non–native plants in the Hawaiian Archipelago

Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

Filamentous tau inclusions are hallmarks of Alzheimer’s disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicityGrant sponsors: NIH AG027476 to Herman Moreno; NS13742/ NS/NINDS/NIH HHS to RLl; FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brasil) projects 2009/01571-6 and CinAPSe 05/56447-7 to Jorge E. Moreira.Peer Reviewe

Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

Filamentous tau inclusions are hallmarks of Alzheimer's disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity

The first 62 AGN observed with SDSS-IV MaNGA -- III: stellar and gas kinematics

We investigate the effects of Active Galactic Nuclei (AGN) on the gas kinematics of their host galaxies, using MaNGA data for a sample of 62 AGN hosts and 109 control galaxies (inactive galaxies). We compare orientation of the line of nodes (kinematic Position Angle - PA) measured from the gas and stellar velocity fields for the two samples. We found that AGN hosts and control galaxies display similar kinematic PA offsets between gas and stars. However, we note that AGN have larger fractional velocity dispersion $\sigma$ differences between gas and stars [$\sigma_{frac}=(\sigma_{\rm gas}-\sigma_{stars})/\sigma_{\rm stars}$] when compared to their controls, as obtained from the velocity dispersion values of the central (nuclear) pixel (2.5" diameter). The AGN have a median value of $\sigma_{\rm frac}$ of $_{\rm AGN}=0.04$, while the the median value for the control galaxies is $_{\rm CTR}=-0.23$. 75% of the AGN show $\sigma_{frac}>-0.13$, while 75% of the normal galaxies show $\sigma_{\rm frac}<-0.04$, thus we suggest that the parameter $\sigma_{\rm frac}$ can be used as an indicative of AGN activity. We find a correlation between the [OIII]$\lambda$5007 luminosity and $\sigma_{frac}$ for our sample. Our main conclusion is that the AGN already observed with MaNGA are not powerful enough to produce important outflows at galactic scales, but at 1-2 kpc scales, AGN feedback signatures are always present on their host galaxies.Comment: 19 pages, 8 figures, published in MNRA

Canonical Correlation Analysis and Partial Least Squares for identifying brain-behaviour associations: a tutorial and a comparative study

Canonical Correlation Analysis (CCA) and Partial Least Squares (PLS) are powerful multivariate methods for capturing associations across two modalities of data (e.g., brain and behaviour). However, when the sample size is similar or smaller than the number of variables in the data, CCA and PLS models may overfit, i.e., find spurious associations that generalise poorly to new data. Dimensionality reduction and regularized extensions of CCA and PLS have been proposed to address this problem, yet most studies using these approaches have some limitations. This work gives a theoretical and practical introduction into the most common CCA/PLS models and their regularized variants. We examine the limitations of standard CCA and PLS when the sample size is similar or smaller than the number of variables. We discuss how dimensionality reduction and regularization techniques address this problem and explain their main advantages and disadvantages. We highlight crucial aspects of the CCA/PLS analysis framework, including optimising the hyperparameters of the model and testing the identified associations for statistical significance. We apply the described CCA/PLS models to simulated data and real data from the Human Connectome Project and the Alzheimer's Disease Neuroimaging Initiative (both of n>500). We use both low and high dimensionality versions of each data (i.e., ratios between sample size and variables in the range of ∼1-10 and ∼0.1-0.01) to demonstrate the impact of data dimensionality on the models. Finally, we summarize the key lessons of the tutorial

Development and validation of a method for the analysis of Ochratoxin A in roasted coffee by liquid chromatography/electrospray-mass spectrometry in Tandem (LC/ESI-MS/MS)

A method using LC/ESI-MS/MS for the quantitative analysis of Ochratoxin A in roasted coffee was described. Linearity was demonstrated (r = 0.9175). The limits of detection and quantification were 1.0 and 3.0 ng g-1, respectively. Trueness, repeatability and intermediate precision values were 89.0-108.8%; 2.4-13.7%; 12.5-17.8%, respectively. To the best of our knowledge, this is the first report in which Ochratoxin A in roasted coffee is analysed by LC/ESI-MS/MS, contributing to the field of mycotoxin analysis, and it will be used for future production of Certified Reference Material