bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the Psychotic Depression Assessment Scale as a Predictor of ECT Outcome
Authors: van Diermen Linda , Versyck Pieter , van den Ameele Seline , Madani Yamina , Vermeulen Tom , Fransen Erik , Sabbe Bernard G. C. , van der Mast Roos C. , Birkenhäger Tom K. , Schrijvers Didier 
Published: June 2019

Objectives
The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor.

Methods
Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors “absence/presence of psychotic symptoms” as the independent variables. Age, episode duration, and treatment resistance were added as covariates.

Results
Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission.

Conclusions
The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression.
ClinicalTrials.gov: Identifier: NCT02562846.
Pseudogene associated recurrent gene fusion in prostate cancer
Authors: Chakravarthi Balabhadrapatruni VSK , Dedigama-Arachchige Pavithra , Carskadon Shannon , Sundaram Shanker Kalyana , Li Jia , Wu Kuan-Han Hank , Chandrashekar Darshan Shimoga , Peabody James , Stricker Hans , Hwang Clara , Chitale Dhananjay , Williamson Sean , Gupta Nilesh , Navone Nora M , Rogers Craig , Menon Mani , Varambally Sooryanarayana , Palanisamy Nallasivam 
Published: June 2019

ABSTRACTAnalysis of next generation transcriptome sequencing data of prostate cancer identified a novel gene fusion formed by the fusion of a protein coding gene (KLK4) with a non-coding pseudogene (KLKP1) and expression of its cognate protein. Screening of 659 prostate cancer TMA showed about 32% of positive cases predominantly expressed in higher Gleason grade tumors. Concomitant expression with ERG but not with SPINK1 and other ETS fusion positive tumors. Fusion gene expression potentially regulated by AR and ERG. Antibody specific to the KLK4-KLKP1 fusion protein was validated by immunohistochemistry and western blot methods. Oncogenic properties were validated by in vitro and in vivo functional studies. Clinical data analysis shows significant association with prostate cancer in young men and overall survival analysis indicate favorable prognosis. Non-invasive detection in urine samples has been confirmed. Taken together, we present a novel biomarker for routine screening of high Gleason grade prostate cancer at diagnosis.SIGNIFICANCEWe discovered and validated a novel prostate cancer (PCa) specific fusion gene involving a protein coding (KLK4) and a pseudogene (KLKP1) and its cognate protein. The unique feature of this fusion gene is the conversion of the noncoding pseudogene into a protein coding gene and its unique expression only in about 30% of high Gleason grade PCa. Expression of this gene is found to be concomitant in ERG fusion positive prostate cancer but mutually exclusive with SPINK1, ETV1, ETV4 and ETV5 positive tumors. Like other ETS family gene fusions, KLK4-KLKP1 can be detected in the urine samples of patients with prostate cancer enabling non-invasive detection of high Gleason grade prostate cancer. Given the unique feature of this fusion oncogenic potential, high Gleason grade specific expression and noninvasive detection, this novel gene fusion has a potential to be used as a biomarker for early detection of high-grade prostate cancer and a therapeutic target.
N1-methyladenine safeguards against aberrant RNA-protein association during proteostasis stress
Authors: Alriquet Marion , Calloni Giulia , Martínez-Limón Adrían , Ponti Riccardo Delli , Hanspach Gerd , Hengesbach Martin , Tartaglia Gian G. , Vabulas R. Martin 
Published: June 2019

AbstractPost-transcriptional modifications of nucleotide bases can effect several aspects of mRNA function. For example, the recent work has established the role of m6A in the coordinated regulation of transcriptome turnover and translation during cellular differentiation and tumorigenesis. The levels of m1A in mRNAs reach up to 10% of those of m6A, yet the functional consequences of this modification are much less clear. Here we show that N1-methyladenine protects mRNAs against aberrant interactions during heat shock and amyloidogenesis in mammalian cells. The m1A methylation motif correlated with the enhanced sequestration of transcripts in stress granules (SG). The cognate methyltransferase TRMT6/61A accumulated and m1A was enriched in SG. Downregulation of the catalytic subunit TRMT61A enhanced amyloidogenesis in the cytosol and increased bystander protein and RNA co-aggregation with Aβ aggregates. Faulty granulation of mutant RNAs has been implicated in pathogenesis of protein aggregation disorders. Our results demonstrate that also normal mRNAs succumb to co-aggregation with proteins if RNA dynamics during stress is disturbed due to the insufficient N1-adenine methylation.
Midkine-a is required for cell cycle progression of Müller glia during neuronal regeneration
Authors: Nagashima Mikiko , D’Cruz Travis S. , Hesse Doneen , Sifuentes Christopher J. , Raymond Pamela A. , Hitchcock Peter F. 
Published: June 2019

SummaryIn zebrafish, Müller glia function as intrinsic retinal stem cells that can regenerate ablated neurons. Understanding the mechanisms governing neuronal stem cells may provide clues to regenerate neurons in mammals. We report that in Müller glia the cytokine/growth factor, Midkine-a, functions as a core autocrine regulator of the cell cycle. Utilizing midkine-a mutants, we determined that Midkine-a regulates elements of an Id2a-retinoblastoma network in reprogrammed Müller glia that controls the expression of cell cycle genes and is required for transition from G1 to S phases of the cell cycle. In mutants, Müller glia that fail to divide undergo reactive gliosis, a pathological hallmark of Müller glia in mammals. Finally, we show that activation of the Midkine-a receptor, ALK, is required for Müller glia proliferation. These data provide mechanistic insights into Müller glia stem cells in the vertebrate retina and suggest avenues for eliciting neuronal regeneration in mammals.
Gli2 is necessary for migration of ventral Neural Stem Cells to demyelinated lesions
Authors: Radecki Daniel Z. , Messling Heather , Haggerty-Skeans James R. , Samanta Jayshree , Salzer James L. 
Published: June 2019

SUMMARYEnhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells in the sub-ventricular zone are marked by Gli1 expression and do not generate oligodendrocytes. However, in response to demyelination they migrate to lesions and differentiate into oligodendrocytes. Inhibition of Gli1 further increases their contribution to remyelination. Gli1 and Gli2 are both transcriptional effectors of the Sonic Hedgehog pathway with highly conserved domains but the role of Gli2 in remyelination by ventral neural stem cells is not clear. Here we show that while genetic ablation of Gli1 in the ventral neural stem cells increases remyelination, loss of Gli2 in these cells decreases their migration to the white matter lesion and reduces their differentiation into mature oligodendrocytes. These studies indicate Gli1 and Gli2 have distinct, non-redundant functions in NSCs, including that Gli2 is essential for the enhanced remyelination mediated by Gli1 inhibition. They highlight the importance of designing specific Gli1 inhibitors that do not inhibit Gli2 as a strategy for therapies targeting the Shh pathway.Graphical Abstract
Shiny-SoSV: A web-based performance calculator for somatic structural variant detection
Authors: Gong Tingting , Hayes Vanessa M , Chan Eva KF 
Published: June 2019

AbstractSomatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools for guiding study design nor are there applications that could predict the performance of somatic structural variant detection. To address this gap, we developed Shiny-SoSV, a user-friendly web-based calculator for determining the impact of common variables on the sensitivity and precision of somatic structural variant detection, including choice of variant detection tool, sequencing depth of coverage, variant allele fraction, and variant breakpoint resolution. Using simulation studies, we determined singular and combinatoric effects of these variables, modelled the results using a generalised additive model, allowing structural variant detection performance to be predicted for any combination of predictors. Shiny-SoSV provides an interactive and visual platform for users to easily compare individual and combined impact of different parameters. It predicts the performance of a proposed study design, on somatic structural variant detection, prior to the commencement of benchwork. Shiny-SoSV is freely available at https://hcpcg.shinyapps.io/Shiny-SoSV with accompanying user’s guide and example use-cases.
An improved pig reference genome sequence to enable pig genetics and genomics research
Authors: Warr Amanda , Affara Nabeel , Aken Bronwen , Beiki H. , Bickhart Derek M. , Billis Konstantinos , Chow William , Eory Lel , Finlayson Heather A. , Flicek Paul , Girón Carlos G. , Griffin Darren K. , Hall Richard , Hannum Greg , Hourlier Thibaut , Howe Kerstin , Hume David A. , Izuogu Osagie , Kim Kristi , Koren Sergey , Liu Haibou , Manchanda Nancy , Martin Fergal J. , Nonneman Dan J. , O’Connor Rebecca E. , Phillippy Adam M. , Rohrer Gary A. , Rosen Benjamin D. , Rund Laurie A. , Sargent Carole A. , Schook Lawrence B. , Schroeder Steven G. , Schwartz Ariel S. , Skinner Ben M. , Talbot Richard , Tseng Elizabeth , Tuggle Christopher K. , Watson Mick , Smith Timothy P. L. , Archibald Alan L. 
Published: June 2019

AbstractThe domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limited its utility. We present two annotated highly contiguous chromosome-level genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.
Biphasic impact of prenatal inflammation and macrophage depletion on the wiring of neocortical inhibitory circuits
Authors: Thion Morgane Sonia , Mosser Coralie-Anne , Férézou Isabelle , Grisel Pauline , Baptista Sofia , Low Donovan , Ginhoux Florent , Garel Sonia , Audinat Etienne 
Published: June 2019

SUMMARYThe etiology of neurodevelopmental disorders is linked to defects in Parvalbumin (PV)-expressing cortical interneurons and to prenatal immune challenges. Mouse models of maternal immune activation (MIA) and microglia deficits increase the postnatal density of PV interneurons, raising the question of their functional integration. Here, we show that MIA and embryonic depletion of macrophages including microglia, have a two-step impact on PV interneurons wiring onto their excitatory target neurons in the barrel cortex. In adults, both challenges reduced the inhibitory drive from PV interneurons, as reported in neurodevelopmental disorders. In juveniles, however, we found an increased density of PV neurons, an enhanced strength of unitary connections onto excitatory cells and an aberrant horizontal inhibition with a reduced lateral propagation of sensory inputs in vivo. Our results provide a novel framework for understanding the impact of prenatal immune challenges onto the developmental trajectory of inhibitory circuits that leads to pathological brain wiring.
Matrix metalloproteinase 1 modulates invasive behavior of tracheal branches during ingression intoDrosophilaflight muscles
Authors: Sauerwald Julia , Backer Wilko , Matzat Till , Schnorrer Frank , Luschnig Stefan 
Published: June 2019

SUMMARYTubular networks like the vasculature extend branches throughout the bodies of animals, but how developing vessels interact with and invade tissues is not well understood. We investigated the underlying mechanisms using the developing tracheal tube network ofDrosophilaindirect flight muscles (IFMs) as a model. Live imaging revealed that tracheal sprouts invade IFMs directionally with growth-cone-like structures at branch tips. Ramification inside IFMs proceeds until tracheal branches fill the myotube. However, individual tracheal cells occupy largely separate territories, possibly mediated by cell-cell repulsion. Matrix metalloproteinase 1 (MMP1) is required in tracheal cells for normal invasion speed and for the dynamic organization of growth-cone-like branch tips. MMP1 remodels the Collagen IV-containing matrix around branch tips and promotes degradation of Branchless FGF in cultured cells. Thus, tracheal-derived MMP1 may play dual roles in sustaining branch invasion by modulating ECM properties as well as by shaping the distribution of the FGF chemoattractant.
Affective Touch Dimensions: From Sensitivity to Metacognition
Authors: von Mohr Mariana , Kirsch Louise P. , Loh Joey K. , Fotopoulou Aikaterini 
Published: June 2019

AbstractTouch can give rise to different sensations including sensory, emotional and social aspects. Tactile pleasure typically associated with caress-like skin stroking of slow velocities (1-10 cm/s) has been hypothesised to relate to an unmyelinated, slow-conducting C-tactile afferent system (CT system), developed to distinguish affective touch from the ‘‘noise’’ of other tactile information on hairy skin (the so-called ‘social touch hypothesis’). However, to date, there is no psychometric examination of the discriminative and metacognitive processes that contribute to accurate awareness of pleasant touch stimuli. Over two studies (total N= 194), we combined for the first time CT stimulation with signal detection theory and metacognitive measurements to assess the social touch hypothesis on the role of the CT system in affective touch discrimination. Participants’ ability to accurately discriminate pleasantness of tactile stimuli of different velocities, as well as their response bias, was assessed using a force-choice task (high versus low pleasantness response) on two different skin sites: forearm (CT-skin) and palm (non-CT skin). We also examined whether such detection accuracy was related to the confidence in their decision (metacognitive sensitivity). Consistently with the social touch hypothesis, we found higher sensitivity d’ on the forearm versus the palm, indicating that people are better at discriminating between stimuli of high and low tactile pleasantness on a skin site that contains CT afferents. Strikingly, we also found more negative response bias on the forearm versus the palm, indicating a tendency to experience all stimuli on CT-skin as ‘high-pleasant’, with such effects depending on order, likely to be explained by prior touch exposure. Finally, we found that people have greater confidence in their ability to discriminate between affective touch stimuli on CT innervated skin than on non-CT skin, possibly relating to the domain specificity of CT touch hence suggesting a domain-specific, metacognitive hypothesis that can be explored in future studies as an extension of the social touch hypothesis.HighlightsTouch mediated by C-tactile (CT) afferents on hairy skin elicits pleasant sensationsWe combine for the first time CT stimulation with signal detection theoryBetter accuracy to detect pleasantness of tactile stimuli at CT optimal speeds on CT skinHigher confidence in ability to accurately distinguish affective touch on CT skin
Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines
Authors: Wang Yan , Marrero Miguel Correa , Medema Marnix H. , van Dijk Aalt D.J. 
Published: June 2019

AbstractPolyketide synthases are multimodular enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by type I polyketide synthases (PKSs), which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein-protein interactions. The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome. Here, we introduce PKSpop, which uses a coevolution-based protein-protein interaction prediction algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (80% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for protein-protein interactions than coevolution between ketosynthase and acyl carrier protein domains.
Evaluation of Open Hollow Hydroxyapatite Microsphere on Bone Regeneration in Rat Calvarial Defects
Authors: Shen Youqu , Rahaman Mohamed , Liu Yongxian , Huang Yue-Wern 
Published: June 2019

AbstractHollow hydroxyapatite (HA) microspheres showed the ability to facilitate bone regeneration in rats with non-healing calvarial defects. However, new bone formation in the rat calvarial defect implanted with the closed HA microspheres was limited. The objective of this work is to evaluate size-, time, and structure-dependent bone regeneration between open and closed HA microspheres in an osseous model. Open HA microspheres were obtained by sectioning closed HA microspheres. The open HA microsphere had dense convex surface and rough and porous concave surface. For both size ranges (ϕ106-150 μm vs. ϕ212-250 μm), the open HA microsphere were more effective in facilitating bone regeneration than the closed HA microspheres in rat calvarial defects. Bone regeneration in the open HA microspheres (49 ± 7% for ϕ106-150 μm; 40 ± 8% for ϕ212-250 μm) were higher than the closed HA microsphere (26 ± 8% for ϕ106-150 μm; 30 ± 9% for ϕ212-250 μm) at 12 weeks. Furthermore, the open HA microspheres of smaller size showed a significant increase in bone regeneration than the open HA microspheres of larger size at both 6 weeks and 12 weeks. The difference in bone regeneration between these microspheres could be due to their differences in microstructures, namely curvature, concavity, porosity, surface roughness, and total surface area available for cells to attached to.
Insulin-like growth factor 1 receptor signaling in tenocytes is required for adult tendon growth
Authors: Disser Nathaniel P , Sugg Kristoffer B , Talarek Jeffrey R , Sarver Dylan C , Rourke Brennan J , Mendias Christopher L 
Published: June 2019

AbstractTenocytes serve to synthesize and maintain collagen fibrils and other matrix proteins in tendon. The underlying biological mechanisms of postnatal tendon growth and repair are not well understood. Insulin-like growth factor 1 (IGF1) plays an important role in the growth and remodeling of numerous tissues, but less is known about IGF1 in tendon. We hypothesized that IGF1 signaling is required for proper tendon growth in response to mechanical loading through regulation of collagen synthesis and cell proliferation. We conditionally deleted the IGF1 receptor (IGF1R) in scleraxis (Scx) expressing tenocytes, and compared to control Scx:IGF1R+ mice, Scx:IGF1RΔ mice demonstrated reduced tenocyte proliferation and smaller tendons in response to mechanical loading. Additionally, we identified that both the PI3K/Akt and ERK pathways are activated downstream of IGF1 and interact in a coordinated manner to regulate cell proliferation and protein synthesis. These studies indicate that IGF1 signaling is required for proper postnatal tendon growth.