Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders

Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically-informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key grey matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant for effective treatment. We demonstrate how this approach can be validated in the treatment of Parkinson’s disease by identifying connectivity patterns that can be used as biomarkers for treatment planning and thus refine the traditional approach of DBS planning that uses only grey matter landmarks. Finally we describe how this approach could be used in planning DBS treatment of psychiatric disorders

Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

Controls on mangrove forest-atmosphere carbon dioxide exchanges in western Everglades National Park

We report on net ecosystem production (NEP) and key environmental controls on net ecosystem exchange (NEE) of carbon dioxide (CO2) between a mangrove forest and the atmosphere in the coastal Florida Everglades. An eddy covariance system deployed above the canopy was used to determine NEE during January 2004 through August 2005. Maximum daytime NEE ranged from −20 to −25 mmol (CO2) m−2 s−1 between March and May. Respiration (Rd) was highly variable (2.81 ± 2.41 mmol (CO2) m−2 s−1), reaching peak values during the summer wet season. During the winter dry season, forest CO2 assimilation increased with the proportion of diffuse solar irradiance in response to greater radiative transfer in the forest canopy. Surface water salinity and tidal activity were also important controls on NEE. Daily light use efficiency was reduced at high (\u3e34 parts per thousand (ppt)) compared to low (ppt) salinity by 46%. Tidal inundation lowered daytime Rd by ∼0.9 mmol (CO2) m−2 s−1 and nighttime Rd by ∼0.5 mmol (CO2) m−2 s−1. The forest was a sink for atmospheric CO2, with an annual NEP of 1170 ± 127 g C m−2 during 2004. This unusually high NEP was attributed to year‐round productivity and low ecosystem respiration which reached a maximum of only 3 g C m−2 d−1. Tidal export of dissolved inorganic carbon derived from belowground respiration likely lowered the estimates of mangrove forest respiration. These results suggest that carbon balance in mangrove coastal systems will change in response to variable salinity and inundation patterns, possibly resulting from secular sea level rise and climate change. Citation: Barr, J. G., V. Engel, J. D. Fuentes

Spitzer-IRS Spectroscopy of the Prototypical Starburst Galaxy NGC7714

We present observations of the starburst galaxy NGC 7714 with the Infrared Spectrograph IRS on board the Spitzer Space Telescope. The spectra yield a wealth of ionic and molecular features that allow a detailed characterization of its properties. NGC 7714 has an HII region-like spectrum with strong PAH emission features. We find no evidence for an obscured active galactic nucleus, and with [NeIII]/[NeII]~0.73, NGC7714 lies near the upper end of normal-metallicity starburst galaxies. With very little slicate absorption and a temperature of the hottest dust component of 340K, NGC 7714 is the perfect template for a young, unobscured starburstComment: To appear in the special ApJSS issue on early results from Spitze

New Observations of Extra-Disk Molecular Gas in Interacting Galaxy Systems, Including a Two-Component System in Stephan's Quintet

We present new CO (1 - 0) observations of eleven extragalactic tails and bridges in nine interacting galaxy systems, almost doubling the number of such features with sensitive CO measurements. Eight of these eleven features were undetected in CO to very low CO/HI limits, with the most extreme case being the NGC 7714/5 bridge. This bridge contains luminous H II regions and has a very high HI column density (1.6 X 10^21 cm^-2 in the 55" CO beam), yet was undetected in CO to rms T(R)* = 2.4 mK. The HI column density is higher than standard H2 and CO self-shielding limits for solar-metallicity gas, suggesting that the gas in this bridge is metal-poor and has an enhanced N(H2)/I(CO) ratio compared to the Galactic value. Only one of the eleven features in our sample was unambiguously detected in CO, a luminous HI-rich star formation region near an optical tail in the compact group Stephan's Quintet. We detect CO at two widely separated velocities in this feature, at ~6000 km/s and ~6700 km/s. Both of these components have HI and H-alpha counterparts. These velocities correspond to those of galaxies in the group, suggesting that this gas is material that has been removed from two galaxies in the group. The CO/HI/H-alpha ratios for both components are similar to global values for spiral galaxies.Comment: 39 pages, Latex, 15 figures, Astronomical Journal, in pres

ISO observations of Hickson Compact Group 31 with the central Wolf-Rayet galaxy NGC 1741

Hickson Compact Group (HCG) 31, consisting of the Wolf-Rayet galaxy NGC 1741 and its irregular dwarf companions, was observed using the Infrared Space Observatory. The deconvolved ISOCAM maps of the galaxies using the 7.7 micron and 14.3 micron (LW6 and LW3) filters are presented, along with ISOPHOT spectrometry of the central starburst region of NGC 1741 and the nucleus of galaxy HCG 31A. Strong mid-IR emission was detected from the central burst in NGC 1741, along with strong PAH features and a blend of features including [S IV] at 10.5 micron. The 14.3/6.75 micron flux ratio, where the 6.75 micron flux was synthesized from the PHT-S spectrum, and 14.3/7.7 micron flux ratios suggest that the central burst within NGC 1741 may be moving towards the post-starburst phase. Diagnostic tools including the ratio of the integrated PAH luminosity to the 40 to 120 micron infrared luminosity and the far-infrared colours reveal that despite the high surface brightness of the nucleus, the properties of NGC 1741 can be explained in terms of a starburst and do not require the presence of an AGN. The Tycho catalogue star TYC 04758-466-1, with m$_{V}$ = 11.3 and spectral type F6, was detected at 7.7 and 14.3 microns.Comment: 27 pages, 7 figures. Accepted for publication in the Astrophysical Journa

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

The Herschel Exploitation of Local Galaxy Andromeda (HELGA). I: Global far-infrared and sub-mm morphology

We have obtained Herschel images at five wavelengths from 100 to 500 micron of a ~5.5x2.5 degree area centred on the local galaxy M31 (Andromeda), our nearest neighbour spiral galaxy, as part of the Herschel guaranteed time project "HELGA". The main goals of HELGA are to study the characteristics of the extended dust emission, focusing on larger scales than studied in previous observations of Andromeda at an increased spatial resolution, and the obscured star formation. In this paper we present data reduction and Herschel maps, and provide a description of the far-infrared morphology, comparing it with features seen at other wavelengths. We use high--resolution maps of the atomic hydrogen, fully covering our fields, to identify dust emission features that can be associated to M31 with confidence, distinguishing them from emission coming from the foreground Galactic cirrus. Thanks to the very large extension of our maps we detect, for the first time at far-infrared wavelengths, three arc-like structures extending out to ~21, ~26 and ~31 kpc respectively, in the south-western part of M31. The presence of these features, hosting ~2.2e6 Msol of dust, is safely confirmed by their detection in HI maps. Overall, we estimate a total dust mass of ~5.8e7 Msol, about 78% of which is contained in the two main ring-like structures at 10 and 15 kpc, at an average temperature of 16.5 K. We find that the gas-to-dust ratio declines exponentially as a function of the galacto-centric distance, in agreement with the known metallicity gradient, with values ranging from 66 in the nucleus to ~275 in the outermost region. [Abridged]Comment: 15 Pages, 9 Figures. Accepted for publication in Astronomy and Astrophysics. A high resolution version of the paper can be found at http://wazn.ugent.be/jfritz/HelgaI_final.pd

Program analysis is harder than verification: A computability perspective

We study from a computability perspective static program analysis, namely detecting sound program assertions, and verification, namely sound checking of program assertions. We first design a general computability model for domains of program assertions and correspond- ing program analysers and verifiers. Next, we formalize and prove an instantiation of Rice\u2019s theorem for static program analysis and verifica- tion. Then, within this general model, we provide and show a precise statement of the popular belief that program analysis is a harder prob- lem than program verification: we prove that for finite domains of pro- gram assertions, program analysis and verification are equivalent prob- lems, while for infinite domains, program analysis is strictly harder than verification

Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine (n=49). We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza (n=54), and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). We demonstrate that circulating markers of complement activation are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials