Translational insights into the genetic etiology of mental health disorders: Examining risk factor models, neuroimaging, and current dissemination practices

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a translation-genetic competence gap whereby genetic knowledge reinforces linear frameworks and genetic competence is needed to achieve effective translation in this content area. Second, a new risk factor model for social anxiety was created that incorporated genetic, environmental, and neurophysiological risk factors (behavioral inhibition, parental bonding, emotion reactivity). Findings indicate that genetic etiology is more informative knowledge that can influence risk factor models and possibly prevention and intervention efforts for social anxiety. Overall this dissertation paves the way for examining the translational capacity of psychiatric genetics in a clinical setting. It constitutes the first examination of barriers to and a potential solution for the most effective translation of psychiatric genetic information

Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane

p53 is a transcription factor that induces growth arrest or apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after γ-irradiation of whole animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent apoptosis

The truth about torsion in the CM case

We show that the upper order of the size of the torsion subgroup of a CM elliptic curve over a degree d number field is d log log d.Comment: 6 pages. This is a minor revision incorporating expository suggestions made by the refere

Avian cerebellar floccular fossa size is not a proxy for flying ability in birds

Extinct animal behavior has often been inferred from qualitative assessments of relative brain region size in fossil endocranial casts. For instance, flight capability in pterosaurs and early birds has been inferred from the relative size of the cerebellar flocculus, which in life protrudes from the lateral surface of the cerebellum. A primary role of the flocculus is to integrate sensory information about head rotation and translation to stabilize visual gaze via the vestibulo-occular reflex (VOR). Because gaze stabilization is a critical aspect of flight, some authors have suggested that the flocculus is enlarged in flying species. Whether this can be further extended to a floccular expansion in highly maneuverable flying species or floccular reduction in flightless species is unknown. Here, we used micro computed-tomography to reconstruct “virtual” endocranial casts of 60 extant bird species, to extract the same level of anatomical information offered by fossils. Volumes of the floccular fossa and entire brain cavity were measured and these values correlated with four indices of flying behavior. Although a weak positive relationship was found between floccular fossa size and brachial index, no significant relationship was found between floccular fossa size and any other flight mode classification. These findings could be the result of the bony endocranium inaccurately reflecting the size of the neural flocculus, but might also reflect the importance of the flocculus for all modes of locomotion in birds. We therefore conclude that the relative size of the flocculus of endocranial casts is an unreliable predictor of locomotor behavior in extinct birds, and probably also pterosaurs and non-avian dinosaurs

Risk analysis to support operation and maintenance of an ageing dock-gate for the Port of Marseille Authority

The dry dock n°10 is a strategic infrastructure of the Port of Marseille Authority: its dimensions (465 x 85 m) place it among the biggest dry docks in Europe. Built in the seventies, it is isolated from the sea by a dock-gate in prestressed concrete. Faced to the ageing of this dock-gate, the Port of Marseille Authority wished to make the most of its knowledge in order to assess the feasibility of two considered operation scenarios: use the dry dock for ship repair or for building new civil engineering structures. In this context, OXAND and the Port of Marseille Authority worked together so as to obtain formal and objective decision-making indicators. These indicators took into account the different operation stakes of the dry dock (security, availability), the condition diagnosis and the ageing prognosis of components and facilities of the dock-gate, along with adapted maintenance actions and related costs. The risk analysis methodology used for this study allowed (1) to characterize the risks linked to each foreseen operation scenario, (2) to identify the most appropriate actions to control these risks, integrating operation constraints (e.g.: need to put the dock-gate in dry dock), (3) to rank these actions regarding their cost/benefit ratio and thus (4), to build a maintenance plan

Unital quantum operators on the Bloch ball and Bloch region

For one qubit systems, we present a short, elementary argument characterizing unital quantum operators in terms of their action on Bloch vectors. We then show how our approach generalizes to multi-qubit systems, obtaining inequalities that govern when a ``diagonal'' superoperator on the Bloch region is a quantum operator. These inequalities are the n-qubit analogue of the Algoet-Fujiwara conditions. Our work is facilitated by an analysis of operator-sum decompositions in which negative summands are allowed.Comment: Revised and corrected, to appear in Physical Review

New Nd-142 Evidence for a Non-Chondritic Composition of the Moon

The coupled Sm-147,146-Nd-143,142 systematics of lunar samples has been extensively studied for estimating the timescale of lunar differentiation. The published datasets yield consistent ages for Nd isotopic closure within the lunar mantle of approx.200 Myr after CAI formation. Although this time constraint is consistent with estimates derived from Hf-W chronometry of the Moon (>60 Myr after CAI formation), there is debate as to whether this age has chronological significance. Furthermore, there are discrepancies regarding the Nd isotope composition of the bulk Moon. Rankenburg et al. obtained a epsilon Nd-142 vs. Sm-147/Nd-144 correlation for lunar samples passing though the chondritic reference value (Sm-147/Nd-144 = 0.1967, epsilon Nd-142 = -0.21), suggesting that the Moon has a chondritic bulk composition. In contrast, the other datasets define a correlation line that passes approx.10-20 ppm above, suggesting that the Moon has a superchondritic Sm-147/Nd-144 (approx.0.206), close to that of the early depleted Earth (EDM). We present new Sm-Nd data for a high-Ti mare basalt (70135), two low-Ti mare basalt (LAP 02205 and MIL 05035) and a KREEPy low-Ti mare basalt (NWA 2977). These data are used to evaluate the significance of the Sm-Nd systematics for constraining the timescale of lunar differentiation and the bulk Nd isotope composition of the Moon