bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemically defined and xenogeneic-free differentiation of human pluripotent stem cells into definitive endoderm in 3D culture
Authors: Diekmann Ulf , Wolling Hanna , Dettmer Rabea , Niwolik Isabell , Naujok Ortwin , Buettner Falk F. R. 
Published: January 2019

AbstractIn vitro differentiation of human pluripotent stem cells (hPSCs) into definitive endoderm (DE) represents a key step towards somatic cells of lung, liver and pancreas. For future clinical applications, mass production of differentiated cells at chemically defined conditions and free of xenogeneic substances is envisioned. In this study we adapted our previously published two-dimensional (2D) DE induction protocol to three-dimensional (3D) static suspension culture in the absence of the xenogeneic extracellular matrix Matrigel. Next, fetal calf serum and bovine serum albumin present in the standard medium were replaced by a custom-made and xeno-free B-27. This yielded in a chemically defined and xenogeneic-free 3D culture protocol for differentiation of hPSCs into DE at efficiencies similar to standard 2D conditions. This novel protocol successfully worked with different hPSC lines including hESCs and hiPSCs maintained in two different stem cell media prior to differentiation. DE cells obtained by our novel BSA-free 3D protocol could be further differentiated into PDX1- or NKX6.1-expressing pancreatic progenitor cells. Notably, upon DE differentiation, we also identified a CXCR4+/NCAM+/EpCAMlow cell population with reduced DE marker gene expression. These CXCR4+/NCAM+/EpCAMlow cells emerge as a result of Wnt/beta-catenin hyperactivation via elevated CHIR-99021 concentrations and likely represent misspecified DE.
Intelectin 3 is dispensable for resistance against a mycobacterial infection in zebrafish (Danio rerio)
Authors: Ojanen Markus J. T. , Uusi-Mäkelä Meri I. E. , Harjula Sanna-Kaisa E. , Saralahti Anni K. , Oksanen Kaisa E. , Kähkönen Niklas , Määttä Juha A. E. , Hytönen Vesa P. , Pesu Marko , Rämet Mika 
Published: January 2019

AbstractTuberculosis is a multifactorial bacterial disease, which can be modeled in the zebrafish (Danio rerio). Abdominal cavity infection withMycobacterium marinum, a close relative ofMycobacterium tuberculosis, leads to a granulomatous disease in adult zebrafish, which replicates the different phases of human tuberculosis, including primary infection, latency and spontaneous reactivation. Here, we have carried out a transcriptional analysis of zebrafish challenged with low-dose ofM. marinum, and identifiedintelectin 3(itln3) among the highly up-regulated genes. In order to clarify thein vivosignificance of Itln3 in immunity, we created nonsenseitln3mutant zebrafish by CRISPR/Cas9 mutagenesis and analyzed the outcome ofM. marinuminfection in both zebrafish embryos and adult fish. The lack of functionalitln3did not affect survival or the mycobacterial burden in the zebrafish. Furthermore, embryonic survival was not affected when another mycobacterial challenge responsiveintelectin,itln1, was silenced using morpholinos either in the WT oritln3mutant fish. In addition,M. marinuminfection in dexamethasone-treated adult zebrafish, which have lowered lymphocyte counts, resulted in similar bacterial burden in both WT fish and homozygousitln3mutants. Collectively, althoughitln3expression is induced uponM. marinuminfection in zebrafish, it is dispensable for protective mycobacterial immune response.
Serotonin transporter binding is increased in Tourette syndrome with Obsessive Compulsive Disorder
Authors: Müller-Vahl K. R. , Szejko N. , Wilke F. , Jakubovski E. , Geworski L. , Bengel F. , Berding G. 
Published: January 2019

AbstractWhile the importance of the serotonergic system in obsessive compulsive disorder (OCD) is well established, its role in Tourette syndrome (TS) is uncertain. Particularly in TS patients with comorbid OCD (TS + OCD), decreased serotonin transporter (SERT) binding has been suggested. Here, we investigated for the first time SERT binding in TS patients with and without OCD (TS − OCD) compared to both healthy controls (HC) and OCD patients as well as the influence of escitalopram using the potent SERT imaging ligand [123I]2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([123I]ADAM) and single-photon emission tomography (SPECT). We included 33 adult subjects (10 HC, 10 TS − OCD, 8 TS + OCD and 5 OCD). In patients with OCD and TS + OCD [123I]ADAM SPECT was repeated after 12–16 weeks treatment with escitalopram. SERT binding was normal in patients with OCD and TS − OCD, but significantly increased (p < 0.05) in those with TS + OCD, particularly in caudate and midbrain compared to both HC and TS − OCD. Treatment with escitalopram resulted in a significant overall reduction in SERT binding (range, 19 to 79%, p values between 0.0409 and <0.0001) without any correlation with clinical improvement. Our results provide further evidence that alterations in the serotonergic system in TS are related to comorbid OCD and do not represent the primary cause of the disease.
The role of metalloproteases in fertilisation in the ascidian Ciona robusta
Authors: Nakazawa Shiori , Shirae-Kurabayashi Maki , Sawada Hitoshi 
Published: January 2019

AbstractIn the ascidian Ciona robusta (formerly C. intestinalis type A), the mechanism underlying sperm penetration through the egg investment remains unknown. We previously reported that proteins containing both an astacin metalloprotease domain and thrombospondin type 1 repeats are abundant in the sperm surface protein-enriched fraction of C. robusta. Here we investigated the involvement of those proteins in fertilisation. We refined the sequences of astacin metalloproteases, confirmed that five of them are present in the sperm, and labelled them as tunicate astacin and thrombospondin type 1 repeat-containing (Tast) proteins. Fertilisation of C. robusta eggs was potently inhibited by a metalloprotease inhibitor GM6001. The eggs cleaved normally when they were vitelline coat-free or the inhibitor was added after insemination. Furthermore, vitelline coat proteins were degraded after incubation with intact sperm. These results suggest that sperm metalloproteases are indispensable for fertilisation, probably owing to direct or indirect mediation of vitelline-coat digestion during sperm penetration. TALEN-mediated knockout of Tast genes and the presence of GM6001 impaired larval development at the metamorphic stage, suggesting that Tast gene products play a key role in late development.
QD laser eyewear as a visual field aid in a visual field defect model
Authors: Iyama Chigusa , Shigeno Yuta , Hirano Eri , Kamoshita Mamoru , Nagai Norihiro , Suzuki Misa , Minami Sakiko , Kurihara Toshihide , Sonobe Hideki , Watanabe Kazuhiro , Shinoda Hajime , Tsubota Kazuo , Ozawa Yoko 
Published: January 2019

AbstractVisual field defects interfere with free actions and influence the quality of life of patients with retinitis pigmentosa; the prevalence of this disease is increasing in aging societies. Patients with progressive disease may require visual aids; however, no such devices are currently available. We utilized a retinal projection eyewear system, QD laser eyewear, which includes a projector inside the spectacle frame, to draw the image taken by a connected portable camera with a wide field lens. The images are projected onto the retina using a Maxwellian view optical system, which is not influenced by refractive error or the amount of incident light. Goldmann perimetry and figure recognition tests with the QD laser eyewear showed increased visual field areas and angles, and shortened the time for recognition of the number of figures in a sheet, in a limited visual field model that we developed by using a pin-hole system to simulate the tunnel vision of retinitis pigmentosa in 19 healthy adults. The device supported the quality of vision. Additionally, the visual field defect model used in healthy adults was useful for validating the device in the development stage of the study, to clarify both advantages and future goals for improving the device.
Acute and chronic demyelinated CNS lesions exhibit opposite elastic properties
Authors: Urbanski Mateusz M. , Brendel Matthew B. , Melendez-Vasquez Carmen V. 
Published: January 2019

AbstractIncreased deposition of extracellular matrix (ECM) is a known inhibitor of axonal regrowth and remyelination. Recent in vitro studies have demonstrated that oligodendrocyte differentiation is impacted by the physical properties of the ECM. However, characterization of the mechanical properties of the healthy and injured CNS myelin is challenging, and has largely relied on non-invasive, low-resolution methods. To address this, we have employed atomic force microscopy to perform micro-indentation measurements of demyelinated tissue at cellular scale. Analysis of mouse and human demyelinated brains indicate that acute demyelination results in decreased tissue stiffness that recovers with remyelination; while chronic demyelination is characterized by increased tissue stiffness, which correlates with augmented ECM deposition. Thus, changes in the mechanical properties of the acutely (softer) or chronically (stiffer) demyelinated brain might contribute to differences in their regenerative capacity. Our findings are relevant to the optimization of cell-based therapies aimed at promoting CNS regeneration and remyelination.
Spatial structure of depression in South Africa: A longitudinal panel survey of a nationally representative sample of households
Authors: Cuadros Diego F. , Tomita Andrew , Vandormael Alain , Slotow Rob , Burns Jonathan K. , Tanser Frank 
Published: January 2019

AbstractWider recognition of the mental health burden of disease has increased its importance as a global public health concern. However, the spatial heterogeneity of mental disorders at large geographical scales is still not well understood. Herein, we investigate the spatial distribution of incident depression in South Africa. We assess depressive symptomatology from a large longitudinal panel survey of a nationally representative sample of households, the South African National Income Dynamics Study. We identified spatial clusters of incident depression using spatial scan statistical analysis. Logistic regression was fitted to establish the relationship between clustering of depression and socio-economic, behavioral and disease risk factors, such as tuberculosis. There was substantial geographical clustering of depression in South Africa, with the excessive numbers of new cases concentrated in the eastern part of the country. These clusters overlapped with those of self-reported tuberculosis in the same region, as well as with poorer, less educated people living in traditional rural communities. Herein, we demonstrate, for the first time, spatial structuring of depression at a national scale, with clear geographical ‘hotspots’ of concentration of individuals reporting new depressive symptoms. Such geographical clustering could reflect differences in exposure to various risk factors, including socio-economic and epidemiological factors, driving or reinforcing the spatial structure of depression. Identification of the geographical location of clusters of depression should inform policy decisions.
Creation of haemoglobin A1c direct oxidase from fructosyl peptide oxidase by combined structure-based site specific mutagenesis and random mutagenesis
Authors: Ogawa Noriyuki , Kimura Takehide , Umehara Fumi , Katayama Yuki , Nagai Go , Suzuki Keiko , Aisaka Kazuo , Maruyama Yukie , Itoh Takafumi , Hashimoto Wataru , Murata Kousaku , Ichimura Michio 
Published: January 2019

AbstractThe currently available haemoglobin A1c (HbA1c) enzymatic assay consists of two specific steps: proteolysis of HbA1c and oxidation of the liberated fructosyl peptide by fructosyl peptide oxidase (FPOX). To develop a more convenient and high throughput assay, we devised novel protease-free assay system employing modified FPOX with HbA1c oxidation activity, namely HbA1c direct oxidase (HbA1cOX). AnFPOX-15, a modified FPOX from Aspergillus nidulans, was selected for conversion to HbA1cOX. As deduced from the crystal structure of AnFPOX-15, R61 was expected to obstruct the entrance of bulky substrates. An R61G mutant was thus constructed to open the gate at the active site. The prepared mutant exhibited significant reactivity for fructosyl hexapeptide (F-6P, N-terminal amino acids of HbA1c), and its crystal structure revealed a wider gate observed for AnFPOX-15. To improve the reactivity for F-6P, several mutagenesis approaches were performed. The ultimately generated AnFPOX-47 exhibited the highest F-6P reactivity and possessed HbA1c oxidation activity. HbA1c levels in blood samples as measured using the direct assay system using AnFPOX-47 were highly correlated with the levels measured using the conventional HPLC method. In this study, FPOX was successfully converted to HbA1cOX, which could represent a novel in vitro diagnostic modality for diabetes mellitus.
Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan
Authors: Saji Naoki , Niida Shumpei , Murotani Kenta , Hisada Takayoshi , Tsuduki Tsuyoshi , Sugimoto Taiki , Kimura Ai , Toba Kenji , Sakurai Takashi 
Published: January 2019

AbstractDysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of ‘other’ bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.
A high-throughput integrated microfluidics method enables tyrosine autophosphorylation discovery
Authors: Nevenzal Hadas , Noach-Hirsh Meirav , Skornik-Bustan Or , Brio Lev , Barbiro-Michaely Efrat , Glick Yair , Avrahami Dorit , Lahmi Roxane , Tzur Amit , Gerber Doron 
Published: January 2019

AbstractAutophosphorylation of receptor and non-receptor tyrosine kinases is a common molecular switch with broad implications for pathogeneses and therapy of cancer and other human diseases. Technologies for large-scale discovery and analysis of autophosphorylation are limited by the inherent difficulty to distinguish between phosphorylation and autophosphorylation in vivo and by the complexity associated with functional assays of receptors kinases in vitro. Here, we report a method for the direct detection and analysis of tyrosine autophosphorylation using integrated microfluidics and freshly synthesized protein arrays. We demonstrate the efficacy of our platform in detecting autophosphorylation activity of soluble and transmembrane tyrosine kinases, and the dependency of in vitro autophosphorylation assays on membranes. Our method, Integrated Microfluidics for Autophosphorylation Discovery (IMAD), is high-throughput, requires low reaction volumes and can be applied in basic and translational research settings. To our knowledge, it is the first demonstration of posttranslational modification analysis of membrane protein arrays.
Metamaterial‐based wideband circularly polarised antenna with rotated V‐shaped metasurface for small satellite applications
Authors: Ameen M. , Chaudhary R.K. 
Published: January 2019

This Letter explains the design and development of a wideband circularly polarised (CP) antenna based on composite metamaterial (MTM) structures which are applicable for use in small satellite applications. The presented antenna is based on a modified co‐planar waveguide feeding technique. The proposed antenna unit cell offers compact size due to its MTM property with dimensions of 0.088λ0 × 0.19λ0 at 2.4 GHz. The CP radiation is obtained by placing two composite right/left‐handed transmission line unit cells orthogonally and exciting two orthogonally‐polarised modes simultaneously. A new 4 × 4 unit cell artificial magnetic conductor metasurface is designed with a compact size at the same operating frequency of MTM‐based CP antenna as a ground plane for the proposed antenna, which is found to be increased bandwidth, improved gain, and wider axial ratio bandwidth without altering the antenna compactness. The final antenna obtains an overall dimension of 0.37λ0 × 0.37λ0 × 0.18λ0 at 2.5 GHz. The measured result shows a wider impedance bandwidth of 860 MHz (33.07%), improved axial ratio bandwidth of 410 MHz (15.92%), and a good gain of 5.76 dBic is obtained which are adequate for the use in modern small satellite applications.
Care and education in adolescents with sleep and eating disorders: Experience of the Mediterranean Adolescent Center
Authors: Bat-Pitault F. , Campredon S. , Da Fonseca D. 
Published: January 2019

Eating disorders and school refusal behavior with delayed sleep phase are pathologies associated with very different or even inverse school problems. It is through these two prisms that we will develop the idea of school care, which is being set up in the innovative framework of the Mediterranean Area of the Adolescent, integrating a National Education Unit within the Child and Adolescent Psychiatry unit.
This specific care seems to us interesting in the adolescent because it allows a work in «natural» environment of certain difficulties related to the different psychiatric disorders and seems to us as a help to the revival of the adolescent process.
Adverse effects of eating disorders on the oral health of teenagers
Authors: Colon P. , Cougot N. , Famery C. 
Published: January 2019

Eating disorders in teenager’s population has a wide range of expressions from a large consumption of sodas or sugar, to binge drinking, anorexia nervosa and anorexia bulimia. Tooth wear or high caries risk could be the clinical expression of such harmful habits and the dental clinical examination could be the way for an early diagnosis of eating disorders
In this kind of situation, discussion with the teenager should be preferred. Epidemiological studies have demonstrated a higher prevalence of such eating behaviors especially for teenagers. Vomiting and gastro esophageal reflux to lead to dental erosion could also be correlated to bruxism and attrition. Prevention and interception of harmful habits are the best way to stop teeth degradation purpose restorative procedure is sometimes required.
Orthodontic therapy is a good opportunity for discussion with teenagers to identify risk factors, but an advised selection of biomaterials is also required during the orthodontic treatment.
Sleep bruxism and sleep disorders
in adolescents
Authors: Carra M. C. 
Published: January 2019

Sleep Bruxism, the sleep-related movement disorder of tooth grinding and clenching, is highly reported in pediatrics with a prevalence of up to 40 % during childhood and adolescence. The precise etiology of sleep bruxism remains unknown, but it may involve genetic and psychosocial components (such as anxiety and stress).
Clinicians should be aware that quite often sleep bruxism is associated with other disorders, such as snoring, sleep-disordered breathing, sleep complaints, and behavioral problems. These comorbidities should be investigated, because they may be severe and prolonged if they are not treated.
SB may lead to morning jaw muscle soreness or pain, headache, masticatory muscle hypertrophy, temporomandibular disorders, and tooth wear. Especially in pediatrics, sleep bruxism is usually managed with conservative therapies, such as sleep hygiene, behavioral modifications, biofeedback, familial counseling and, only in cases of severe tooth wear or other serious possible consequences of SB, soft occlusal splints.
Surprising Bone and Soft Tissue Lesions of the Chest: Pictorial Review
Authors: Degrieck Bert , Bazzocchi Alberto , Verstraete Koenraad 
Published: January 2019

AbstractAlthough plain radiographs of the chest are usually requested to evaluate the heart, lung, and mediastinum, many bone and soft tissue, metabolic, and congenital lesions can be visible presenting as surprising lesions. Thorough analysis of the lesion characteristics on the chest radiograph, eventually in conjunction with more advanced imaging techniques and in combination with the clinical findings, will lead to the correct diagnosis.
Differential Diagnosis of Spine Tumors: My Favorite Mistake
Authors: Albano Domenico , Messina Carmelo , Gitto Salvatore , Papakonstantinou Olympia , Sconfienza Luca 
Published: January 2019

AbstractImaging has a pivotal role in the detection and characterization of spine bone tumors (SBTs), especially using magnetic resonance (MR) imaging and computed tomography (CT). Although MR performed with conventional pulse sequences has a robust reliability in the assessment of SBTs, some imaging features of benign lesions and malignancies overlap, making the differential diagnosis challenging. Several imaging tools are now available to perform a correct interpretation of images of SBTs including diffusion-weighted imaging, dynamic contrast-enhanced MR, Dixon sequences, and dual-energy CT. Nevertheless, strengths and weaknesses of imaging modalities should be kept in mind, and it is crucial to be aware of the pitfalls that can be encountered in daily clinical practice when dealing with these lesions. This review provides an overview on the main challenges encountered when dealing with SBTs, providing some tricks of the trade to avoid possible diagnostic traps.