Natural emotion vocabularies and borderline personality disorder

Background Emotion dysregulation is a characteristic central to borderline personality disorder (BPD). Valuably, verbal behaviour can provide a unique perspective for studying emotion dysregulation in BPD, with recent research suggesting that the varieties of emotion words one actively uses (i.e., active emotion vocabularies [EVs]) reflect habitual experience and potential dysregulation therein. Accordingly, the present research examined associations between BPD and active EVs across two studies. Methods Study 1 (N = 530) comprised a large non-clinical sample recruited from online forums, whereby BPD traits were measured via self-report. Study 2 (N = 64 couples) consisted of mixed-gender romantic couples in which the woman had a BPD diagnosis, as well as a control group of couples. In both studies, participants’ verbal behaviours were analysed to calculate their active EVs. Results Results from both studies revealed BPD to be associated with larger negative EV (i.e., using a broad variation of unique negative emotion words), which remained robust when controlling for general vocabulary size and negative affect word frequency in Study 2. The association between BPD and negative EV was insensitive to context. Limitations Limitations of this research include: 1) the absence of a clinical control group; 2) typical constraints surrounding word-counting approaches; and 3) the cross-sectional design (causality cannot be inferred). Conclusions Our findings contribute to BPD theory as well as the broader language and emotion literature. Importantly, these findings provide new insight into how individuals manifesting BPD attend to and represent their emotional experiences, which could be used to inform clinical practice

Lagrangian Variational Framework for Boundary Value Problems

A boundary value problem is commonly associated with constraints imposed on a system at its boundary. We advance here an alternative point of view treating the system as interacting "boundary" and "interior" subsystems. This view is implemented through a Lagrangian framework that allows to account for (i) a variety of forces including dissipative acting at the boundary; (ii) a multitude of features of interactions between the boundary and the interior fields when the boundary fields may differ from the boundary limit of the interior fields; (iii) detailed pictures of the energy distribution and its flow; (iv) linear and nonlinear effects. We provide a number of elucidating examples of the structured boundary and its interactions with the system interior. We also show that the proposed approach covers the well known boundary value problems.Comment: 41 pages, 3 figure

Real-time quantum error correction beyond break-even

The ambition of harnessing the quantum for computation is at odds with the fundamental phenomenon of decoherence. The purpose of quantum error correction (QEC) is to counteract the natural tendency of a complex system to decohere. This cooperative process, which requires participation of multiple quantum and classical components, creates a special type of dissipation that removes the entropy caused by the errors faster than the rate at which these errors corrupt the stored quantum information. Previous experimental attempts to engineer such a process faced an excessive generation of errors that overwhelmed the error-correcting capability of the process itself. Whether it is practically possible to utilize QEC for extending quantum coherence thus remains an open question. We answer it by demonstrating a fully stabilized and error-corrected logical qubit whose quantum coherence is significantly longer than that of all the imperfect quantum components involved in the QEC process, beating the best of them with a coherence gain of $G = 2.27 \pm 0.07$. We achieve this performance by combining innovations in several domains including the fabrication of superconducting quantum circuits and model-free reinforcement learning

Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, pae-diatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telen-cephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants (CNVs) of the ARX locus found in patients presenting wide-ranging phenotypic variations including ID, speech delay, hypotonia and psychiatric abnormalities. We also report on a further novel Xp21.3 duplication detected in a male patient with moderate ID and carrying a fully duplicated copy of the ARX locus and the ultraconserved enhancers. As consequences of this rearrangement, the patient-derived lymphoblastoid cell line shows abnormal activity of the ARX-KDM5C-SYN1 regulatory axis. Moreover, the three-dimensional (3D) structure of the Arx locus, both in mouse embryonic stem cells and cortical neurons, provides new insight for the functional consequences of ARX duplications. Finally, by comparing the clinical features of the 16 CNVs affecting the ARX locus, we conclude that—depending on the involvement of tissue-specific enhancers—the ARX duplications are ID-associated risk CNVs with variable expressivity and penetrance

ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems

ToppCluster is a web server application that leverages a powerful enrichment analysis and underlying data environment for comparative analyses of multiple gene lists. It generates heatmaps or connectivity networks that reveal functional features shared or specific to multiple gene lists. ToppCluster uses hypergeometric tests to obtain list-specific feature enrichment P-values for currently 17 categories of annotations of human-ortholog genes, and provides user-selectable cutoffs and multiple testing correction methods to control false discovery. Each nameable gene list represents a column input to a resulting matrix whose rows are overrepresented features, and individual cells per-list P-values and corresponding genes per feature. ToppCluster provides users with choices of tabular outputs, hierarchical clustering and heatmap generation, or the ability to interactively select features from the functional enrichment matrix to be transformed into XGMML or GEXF network format documents for use in Cytoscape or Gephi applications, respectively. Here, as example, we demonstrate the ability of ToppCluster to enable identification of list-specific phenotypic and regulatory element features (both cis-elements and 3′UTR microRNA binding sites) among tissue-specific gene lists. ToppCluster’s functionalities enable the identification of specialized biological functions and regulatory networks and systems biology-based dissection of biological states. ToppCluster can be accessed freely at http://toppcluster.cchmc.org

Detection of epithelial to mesenchymal transition in airways of a bleomycin induced pulmonary fibrosis model derived from an α-smooth muscle actin-Cre transgenic mouse

BACKGROUND: Epithelial to mesenchymal transition (EMT) in alveolar epithelial cells (AECs) has been widely observed in patients suffering interstitial pulmonary fibrosis. In vitro studies have also demonstrated that AECs could convert into myofibroblasts following exposure to TGF-β1. In this study, we examined whether EMT occurs in bleomycin (BLM) induced pulmonary fibrosis, and the involvement of bronchial epithelial cells (BECs) in the EMT. Using an α-smooth muscle actin-Cre transgenic mouse (α-SMA-Cre/R26R) strain, we labelled myofibroblasts in vivo. We also performed a phenotypic analysis of human BEC lines during TGF-β1 stimulation in vitro. METHODS: We generated the α-SMA-Cre mouse strain by pronuclear microinjection with a Cre recombinase cDNA driven by the mouse α-smooth muscle actin (α-SMA) promoter. α-SMA-Cre mice were crossed with the Cre-dependent LacZ expressing strain R26R to produce the double transgenic strain α-SMA-Cre/R26R. β-galactosidase (βgal) staining, α-SMA and smooth muscle myosin heavy chains immunostaining were carried out simultaneously to confirm the specificity of expression of the transgenic reporter within smooth muscle cells (SMCs) under physiological conditions. BLM-induced peribronchial fibrosis in α-SMA-Cre/R26R mice was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. To confirm in vivo observations of BECs undergoing EMT, we stimulated human BEC line 16HBE with TGF-β1 and examined the localization of the myofibroblast markers α-SMA and F-actin, and the epithelial marker E-cadherin by immunofluorescence. RESULTS: βgal staining in organs of healthy α-SMA-Cre/R26R mice corresponded with the distribution of SMCs, as confirmed by α-SMA and SM-MHC immunostaining. BLM-treated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some AECs in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by α-SMA immunostaining. In vitro, addition of TGF-β1 to 16HBE cells could also stimulate the expression of α-SMA and F-actin, while E-cadherin was decreased, consistent with an EMT. CONCLUSION: We observed airway EMT in BLM-induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis

Multi-institutional Evaluation of Producing and Testing a Novel 3D-Printed Laparoscopic Trainer

To create, distribute, and evaluate the efficacy of a portable, cost effective 3D-printed laparoscopic trainer for surgical skills development.Objective: To create, distribute, and evaluate the efficacy of a portable, cost-effective 3D-printed laparoscopic trainer for surgical skills development. Methods: The UCI Trainer (UCiT) laparoscopic simulator was developed via computer-aided designs (CAD), which were used to 3D-print the UCiT. Once assembled, a tablet computer with a rear-facing camera was attached for video and optics. Four institutions were sent the UCiT CAD files with a 3D-printer and instructions for UCiT assembly. For a comparison of the UCiT to a standard trainer, peg transfer and intracorporeal knot tying skills were accessed. These tasks were scored, and participants were asked to rate their experience with the trainers. Lastly, a questionnaire was given to individuals who 3D-printed and assembled the UCiT. Results: We recruited 25 urologists; none had any 3D-printing experience. The cost of printing each trainer was $26.50 USD. Each institution used the Apple iPad for optics. Six of eight participants assembled the UCiT in < 45 minutes, and rated assembly as somewhat easy. On objective scoring, participants performed tasks equally well on the UCiT vs the conventional trainer. On subjective scoring, the conventional trainer provided a significantly better experience vs the UCiT; however, all reported that the UCiT was useful for surgical education. Conclusion: The UCiT is a low cost, portable training tool that is easy to assemble and use. UCiT provided a platform whereby participants performed laparoscopic tasks equal to performing the same tasks on the more expensive, nonportable standard trainer

Susceptibility of common weeds and cultivated crops in major maize growing agroecological zones of Uganda to viruses causing maize lethal necrosis disease

Maize lethal necrosis (MLN) disease is caused when maize plants become co-infected with Maize chlorotic mottle virus (MCMV) and potyviruses notably Sugarcane Mosaic Virus (SCMV). Apart from maize, little is known about susceptibility of weed species and cultivated crop species usually growing in proximity with maize to MLN viruses in Uganda. The common weeds and crop plants were mechanically inoculated with combined sap from MCMV and SCMV infected maize plants. Samples were tested for MLN causing viruses by Double Antibody Sandwich Enzyme-Linked Immunosorbent Assay (DAS-ELISA) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The weeds that were susceptible to MCMV were Digitaria abyssinica, Eleusine africana and Roetboellia cochinchinensis; while those susceptible to SCMV were Pennisetum purpureum, Panicum maximum and Roetboellia cochinchinensis. The cultivated crops were susceptible only to MCMV and included cassava (Manihot esculenta), groundnut (Arachis hypogaea) and bean (Phaseolus vulgaris). Common weeds and cultivated crops growing close to maize in Uganda have differential susceptibility to MLN causing viruses and can act as reservoirs of MLN causing viruses. It is critical to identify non-MLN hosts in cultivated crops for crop rotation and early weeding to reduce on MLN virus inoculum in cropping syste

Retinoid-Induced Expression and Activity of an Immediate Early Tumor Suppressor Gene in Vascular Smooth Muscle Cells

Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE) located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β) in cultured smooth muscle cells (SMC) as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA) regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall