Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides

International audienceLong non-coding RNAs (lncRNAs) are an emerging class of regulatory RNA that may be implicated in psychiatric disorders. Here we performed RNA-sequencing in the rostral anterior cingulate cortex of 26 depressed suicides and 24 matched controls. We first performed differential lncRNA expression analysis, and then conducted Weighted Gene Co-expression Network Analysis (WGCNA) to identify co-expression modules associating with depression and suicide. We identified 23 differentially expressed lncRNAs (FDR < 0.1) as well as their differentially expressed overlapping and antisense protein-coding genes. Several of these overlapping or antisense genes were associated with interferon signaling, which is a component of the innate immune response. Using WGCNA, we identified modules of highly co-expressed genes associated with depression and suicide and found protein-coding genes highly connected to differentially expressed lncRNAs within these modules. These protein-coding genes were located distal to their associated lncRNAs and were found to be part of several GO terms enriched in the significant modules, which include: cytoskeleton organization, plasma membrane, cell adhesion, nucleus, DNA-binding, and regulation of dendrite development and morphology. Altogether, we report that lncRNAs are differentially expressed in the brains of depressed individuals who died by suicide and may represent regulators of important molecular functions and biological processes

Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides

International audienceThe nociceptin/orphanin FQ (N/OFQ)-Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration

Homeostasis, homeorhesis, and the “logic of life”: Envisaging plasticity and stability in molecular research on trauma and its effects

How does a trait develop, and what makes it persist? This question is at the heart of studies of 21st-century neurosciences that attempt to identify how people develop specific personality traits and how these may become permanently anchored in their neurobiological profiles and temperaments. Such studies have documented the neuromolecular effects of early life adversity and have contributed to an understanding of subsequent life trajectories as being disproportionately affected by early negative experiences. This view has arisen despite little evidence of the stability of the presumably early-developed molecular traits and their potential effects on phenotypes Moreover, the overall understanding of these trajectories raises questions as to the origin of the potential stability of molecular traits: namely, whether they simply persist or whether they are actively maintained, and potentially augmented by, ongoing life adversity. These two perspectives have potentially significant implications for the understanding of the malleability of life trajectories and commitments to support people in shaping their trajectories. Through an analysis of historical and contemporary scientific literature and ethnographic research with neuroscientists, we consider how trauma came to be associated with specific psychological and neurobiological effects grounded in understandings of homeostasis and homeorhesis (trajectories). We then consider the ways in which neuroscientific researchers conceptualize the relationships between early adversity and elevated suicide risk later in life. We conclude with a consideration of the conceptual, ontological, and ethical implications of framing persistent life traits as the result of the persistence of long-embodied biological traits, persistent life environments, or both

The QSO HE0450-2958: Scantily dressed or heavily robed? A normal quasar as part of an unusual ULIRG

(Abridged) The luminous z=0.286 quasar HE0450-2958 is interacting with a companion galaxy at 6.5 kpc distance and the whole system is a ULIRG. A so far undetected host galaxy triggered the hypothesis of a mostly "naked" black hole (BH) ejected from the companion by three-body interaction. We present new HST/NICMOS 1.6micron imaging data at 0.1" resolution and VLT/VISIR 11.3micron images at 0.35" resolution that for the first time resolve the system in the near- and mid-infrared. We combine these with existing optical HST and CO maps. (i) At 1.6micron we find an extension N-E of the quasar nucleus that is likely a part of the host galaxy, though not its main body. If true, this places HE0450-2958 directly onto the M_BH-M_bulge-relation for nearby galaxies. (ii) HE0450-2958 is consistent with lying at the high-luminosity end of Narrow-Line Seyfert 1 Galaxies, and more exotic explanations like a "naked quasar" are unlikely. (iii) All 11.3micron radiation in the system is emitted by the quasar nucleus, which is radiating at super-Eddington rate, L/L_Edd=6.2+3.8-1.8, or 12 M_sun/yr. (iv) The companion galaxy is covered in optically thick dust and is not a collisional ring galaxy. It emits in the far infrared at ULIRG strength, powered by Arp220-like star formation (strong starburst-like). An M82-like SED is ruled out. (v) With its black hole accretion rate HE0450-2958 produces not enough new stars to maintain its position on the M_BH-M_bulge-relation, and star formation and black hole accretion are spatially disjoint; the bulge has to grow by redistribution of preexisting stars. (vi) Systems similar to HE0450-2958 with spatially disjoint ULIRG-strength star formation and quasar activity are rare. At z<0.43 we only find <4% (3/77) candidates for a similar configuration.Comment: 12 pages, 6 figures, accepted for publication in Ap

Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals

The mu opioid receptor (MOR) is a G protein-coupled receptor that plays an essential role in reward and hedonic processes, and that has been implicated in disorders such as depression and addiction. Over the last decade, several brain imaging studies in depressed patients have consistently found that dysregulation of MOR function occurs in particular in the anterior insular cortex, an important brain site for the perception of internal states and emotional regulation. To investigate molecular mechanisms that may underlie these effects, here we assessed genetic polymorphisms, expression, and functional G-protein coupling of MOR in a large post-mortem cohort (N = 95) composed of depressed individuals who died by suicide, and healthy controls. Results indicated that depression, but not comorbid substance use disorder or acute opiate consumption, was associated with increased MOR activity. This effect was partly explained by a specific increase in expression of the inhibitory alpha G-protein subunit GNAI2. Consistent with previous neuroimaging studies, our findings support the notion that enhanced endogenous opioidergic tone in the anterior insula may buffer negative affective states in depressed individuals, a mechanism that could potentially contribute to the antidepressant efficacy of emerging opioid-based medications.journal articleresearch support, non-u.s. gov't2021 042021 02 02importe

Reception Test of Petals for the End Cap TEC+ of the CMS Silicon Strip Tracker

The silicon strip tracker of the CMS experiment has been completed and was inserted into the CMS detector in late 2007. The largest sub system of the tracker are its end caps, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted onto the TEC support structures. Each end cap consists of 144 such petals, which were built and fully qualified by several institutes across Europe. Fro

Integration of the End Cap TEC+ of the CMS Silicon Strip Tracker

The silicon strip tracker of the CMS experiment has been completed and inserted into the CMS detector in late 2007. The largest sub-system of the tracker is its end cap system, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted into the TEC support structures. Each end cap consists of 144 petals, and the insertion of these petals into the end cap structure is referred to as TEC integration. The two end caps were integrated independently in Aachen (TEC+) and at CERN (TEC--). This note deals with the integration of TEC+, describing procedures for end cap integration and for quality control during testing of integrated sections of the end cap and presenting results from the testing

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures