bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an early cell fate regulator by detecting dynamics in transcriptional heterogeneity and co-regulation during astrocyte differentiation
Authors: Ando Tatsuya , Kato Ryuji , Honda Hiroyuki 
Published: May 2019

AbstractThere are an increasing number of reports that characterize the temporal behavior of gene expression at the single-cell level during cell differentiation. Despite accumulation of data describing the heterogeneity of biological responses, the dynamics of gene expression heterogeneity and its regulation during the differentiation process have not been studied systematically. To understand transcriptional heterogeneity during astrocyte differentiation, we analyzed single-cell transcriptional data from cells representing the different stages of astrocyte differentiation. When we compared the transcriptional variability of co-expressed genes between the undifferentiated and differentiated states, we found that there was significant increase in transcriptional variability in the undifferentiated state. The genes showing large changes in both “variability” and “correlation” between neural stem cells (NSCs) and astrocytes were found to be functionally involved in astrocyte differentiation. We determined that these genes are potentially regulated by Ascl1, a previously known oscillatory gene in NSCs. Pharmacological blockade of Ntsr2, which is transcriptionally co-regulated with Ascl1, showed that Ntsr2 may play an important role in the differentiation from NSCs to astrocytes. This study shows the importance of characterizing transcriptional heterogeneity and rearrangement of the co-regulation network between different cell states. It also highlights the potential for identifying novel regulators of cell differentiation that will further increase our understanding of the molecular mechanisms underlying the differentiation process.
A sea-level plateau preceding the Marine Isotope Stage 2 minima revealed by Australian sediments
Authors: Ishiwa Takeshige , Yokoyama Yusuke , Okuno Jun’ichi , Obrochta Stephen , Uehara Katsuto , Ikehara Minoru , Miyairi Yosuke 
Published: May 2019

AbstractFurther understanding of past climate requires a robust estimate of global ice volume fluctuations that in turn rely on accurate global sea-level reconstructions. An advantage of Marine Isotope Stage 2 (MIS 2) is the availability of suitable material for radiocarbon dating to allow comparison of sea-level data with other paleoclimatic proxies. However, the number and accuracy of sea-level records during MIS 2 is currently lacking. Here we present the history of MIS 2 eustatic sea-level change as recorded in the Bonaparte Gulf, northwestern Australia by reconstructing relative sea level and then modeling glacial isostatic adjustment. The isostatically-corrected global sea-level history indicates that sea-level plateaued from 25.9 to 20.4 cal kyr BP (modeled median probability) prior reaching its minimum (19.7 to 19.1 cal kyr BP). Following the plateau, we detect a 10-m global sea-level fall over ~1,000 years and a short duration of the Last Glacial Maximum (global sea-level minimum; 19.7 to 19.1 cal kyr BP). These large changes in ice volume over such a short time indicates that the continental ice sheets never reached their isostatic equilibrium during the Last Glacial Maximum.
v-P2O5 micro-clustering in P-doped silica studied by a first-principles Raman investigation
Authors: Giacomazzi Luigi , Martin-Samos L. , Alessi A. , Richard N. , Boukenter A. , Ouerdane Y. , Girard S. , Valant M. , De Gironcoli S. 
Published: May 2019

AbstractSynthetic vitreous silica is currently the preferred material for the production of optical fibres because of the several excellent properties of this glass, e.g. high transmission in the visible and IR domains, high mechanical strength, chemical durability, and ease of doping with various materials. For instance, fiber lasers and amplifiers exploit the light amplification properties provided by rare-earth ions employed as dopants in the core of silica-based optical fibers. The structure and composition of the nearest neighbor shell surrounding rare-earth ions in silica-based optical fibers and amplifiers have been intensively debated in the last decade. To reduce aggregation effects between rare-earth ions, co-dopants such as phosphorus and aluminium are added as structural modifiers; phosphorus-doping, in particular, has proved to be very efficient in dissolving rare-earth ions. In this work, we provide further insights concerning the embedding of P atoms into the silica network, which may be relevant for explaining the ease of formation of a phosphorus pentoxide nearest-neighbor shell around a rare-earth dopant. In particular, by means of first-principles calculations, we discuss alternative models for an irradiation (UV, x–, γ-rays) induced paramagnetic center, i.e. the so called room-temperature phosphorus-oxygen-hole center, and its precursors. We report that the most likely precursor of a room-temperature phosphorus-oxygen-hole center comprises of a micro-cluster of a few (at least two) neighboring phosphate tetrahedra, and correspondingly that the occurrence of isolated [(O-)2P(=O)2]− units is unlikely even at low P-doping concentrations. In fact, this work predicts that the symmetric stretching of P=O bonds in isolated [(O-)2P(=O)2]− units appears as a Raman band at a frequency of ~1110 cm−1, and only by including at least another corner-sharing phosphate tetrahedron, it is shown to shift to higher frequencies (up to ~40 cm−1) due to the shortening of P=O bonds, thereby leading to an improved agreement with the observed Raman band located at ~1145 cm−1.
Diet quality and depression risk in a Japanese population: the Japan Public Health Center (JPHC)-based Prospective Study
Authors: Okubo Ryo , Matsuoka Yutaka J. , Sawada Norie , Mimura Masaru , Kurotani Kayo , Nozaki Shoko , Shikimoto Ryo , Tsugane Shoichiro 
Published: May 2019

AbstractThe association of overall diet quality based on the Japanese Food Guide Spinning Top with risk of depression is not known. This prospective cohort study aimed to determine whether higher adherence to the Japanese food guide reduced the risk of depression. Of 12,219 residents enrolled at baseline, we extracted 1,112 participants who completed a 5-year follow-up (1995) and participated in a mental health screening (2014–2015). Diet quality was scored based on adherence to the Japanese food guide and the ratio of white to red meat according to the Alternative Healthy Index and ranged from 0 (worst) to 80 (best). We calculated odds ratios and 95% confidence intervals for current psychiatrist-diagnosed depression per quartile of total score and of eight component scores with the lowest quartile as reference. Mean age of the participants was 73 years and 59% were women. Total diet quality score was not significantly associated with risk of depression 20 years after the baseline assessment. Among the eight components on the diet quality score, there was a significantly reduced risk for the highest quartile of the white to red meat ratio score. In conclusion, our results do not indicate that higher adherence to the Japanese food guide prevents depression.
Confidence as a diagnostic tool for perceptual aftereffects
Authors: Gallagher Regan M. , Suddendorf Thomas , Arnold Derek H. 
Published: May 2019

AbstractPerceptual judgements are, by nature, a product both of sensation and the cognitive processes responsible for interpreting and reporting subjective experiences. Changed perceptual judgements may thus result from changes in how the world appears (perception), or subsequent interpretation (judgement). This ambiguity has led to persistent debates about how to interpret changes in decision-making, and if higher-order cognitions can change how the world looks, or sounds, or feels. Here we introduce an approach that can help resolve these ambiguities. In three motion-direction experiments, we measured perceptual judgements and subjective confidence. We show that each measure is sensitive to sensory information and can index sensory adaptation. Each measure is also sensitive to decision biases, but response bias impacts the central tendency of decision and confidence distributions differently. Our findings show that subjective confidence, when measured in addition to perceptual decisions, can supply important diagnostic information about the cause of aftereffects.
Platelet function in HIV plus dengue coinfection associates with reduced inflammation and milder dengue illness
Authors: Hottz Eugenio D. , Quirino-Teixeira Anna Cecíllia , Valls-de-Souza Rogério , Zimmerman Guy A. , Bozza Fernando A. , Bozza Patrícia T. 
Published: May 2019

AbstractHIV-infected subjects under virological control still exhibit a persistent proinflammatory state. Thus, chronic HIV infection changes the host homeostasis towards an adapted immune response that may affect the outcome of coinfections. However, little is known about the impact of HIV infection on inflammatory amplification and clinical presentation in dengue. Platelets have been shown to participate in immune response in dengue and HIV. We hypothesized that altered platelet responses in HIV-infected subjects may contribute to altered inflammatory milieu and disease progression in dengue. We prospectively followed a cohort of 84 DENV-infected patients of whom 29 were coinfected with HIV under virological control. We report that dengue and HIV coinfection progress with reduced inflammation and milder disease progression with lower risk of vascular instability. Even though the degree of thrombocytopenia and platelet activation were similar between dengue-infected and HIV plus dengue-coinfected patients, plasma levels of the platelet-derived chemokines RANTES/CCL5 and PF4/CXCL4 were lower in coinfection. Consistently, platelets from coinfected patients presented defective secretion of the stored-chemokines PF4 and RANTES, but not newly synthesized IL-1β, when cultured ex vivo. These data indicate that platelets from HIV-infected subjects release lower levels of chemokines during dengue illness, which may contribute to milder clinical presentation during coinfection.
Simultaneous Quantitation of Cationic and Non-ionic Contrast Agents in Articular Cartilage Using Synchrotron MicroCT Imaging
Authors: Saukko Annina E. A. , Turunen Mikael J. , Honkanen Miitu K. M. , Lovric Goran , Tiitu Virpi , Honkanen Juuso T. J. , Grinstaff Mark W. , Jurvelin Jukka S. , Töyräs Juha 
Published: May 2019

AbstractEarly diagnosis of acute cartilage injuries enables monitoring of disease progression and improved treatment option planning to prevent post-traumatic osteoarthritis. In contrast-enhanced computed tomography (CECT), the changes in cationic agent diffusion within the tissue reflect cartilage degeneration. The diffusion in degenerated cartilage depends on proteoglycan (PG) content and water content, but each having an opposite effect on diffusion, thus compromising the diagnostic sensitivity. To overcome this limitation, we propose the simultaneous imaging of cationic (sensitive to PG and water contents) and non-ionic (sensitive to water content) agents. In this study, quantitative dual-energy CT (QDECT) imaging of two agents is reported for the first time at clinically feasible imaging time points. Furthermore, this is the first time synchrotron microCT with monochromatic X-rays is employed in cartilage CECT. Imaging was conducted at 1 and 2 h post contrast agent immersion. Intact, PG-depleted, and mechanically injured + PG-depleted cartilage samples (n = 33) were imaged in a mixture of cationic (iodine-based CA4+) and non-ionic (gadolinium-based gadoteridol) agents. Concurrent evaluation of CA4+ and gadoteridol partitions in cartilage is accomplished using QDECT. Subsequent normalization of the CA4+ partition with that of the gadoteridol affords CA4+ attenuations that significantly correlate with PG content – a key marker of OA.
Microbiota alter metabolism and mediate neurodevelopmental toxicity of 17β-estradiol
Authors: Catron Tara R. , Swank Adam , Wehmas Leah C. , Phelps Drake , Keely Scott P. , Brinkman Nichole E. , McCord James , Singh Randolph , Sobus Jon , Wood Charles E. , Strynar Mark , Wheaton Emily , Tal Tamara 
Published: May 2019

AbstractEstrogenic chemicals are widespread environmental contaminants associated with diverse health and ecological effects. During early vertebrate development, estrogen receptor signaling is critical for many different physiologic responses, including nervous system function. Recently, host-associated microbiota have been shown to influence neurodevelopment. Here, we hypothesized that microbiota may biotransform exogenous 17-βestradiol (E2) and modify E2 effects on swimming behavior. Colonized zebrafish were continuously exposed to non-teratogenic E2 concentrations from 1 to 10 days post-fertilization (dpf). Changes in microbial composition and predicted metagenomic function were evaluated. Locomotor activity was assessed in colonized and axenic (microbe-free) zebrafish exposed to E2 using a standard light/dark behavioral assay. Zebrafish tissue was collected for chemistry analyses. While E2 exposure did not alter microbial composition or putative function, colonized E2-exposed larvae showed reduced locomotor activity in the light, in contrast to axenic E2-exposed larvae, which exhibited normal behavior. Measured E2 concentrations were significantly higher in axenic relative to colonized zebrafish. Integrated peak area for putative sulfonated and glucuronidated E2 metabolites showed a similar trend. These data demonstrate that E2 locomotor effects in the light phase are dependent on the presence of microbiota and suggest that microbiota influence chemical E2 toxicokinetics. More broadly, this work supports the concept that microbial colonization status may influence chemical toxicity.
Rim-to-Disc Ratio Outperforms Cup-to-Disc Ratio for Glaucoma Prescreening
Authors: Kumar J. R. Harish , Seelamantula Chandra Sekhar , Kamath Yogish Subraya , Jampala Rajani 
Published: May 2019

AbstractWe present a novel and fully automated fundus image processing technique for glaucoma prescreening based on the rim-to-disc ratio (RDR). The technique accurately segments the optic disc and optic cup and then computes the RDR based on which it is possible to differentiate a normal fundus from a glaucomatous one. The technique performs a further categorization into normal, moderate, or severely glaucomatous classes following the disc-damage-likelihood scale (DDLS). To the best of our knowledge, this is the first engineering attempt at using RDR and DDLS to perform glaucoma severity assessment. The segmentation of the optic disc and cup is based on the active disc, whose parameters are optimized to maximize the local contrast. The optimization is performed efficiently by means of a multiscale representation, accelerated gradient-descent, and Green’s theorem. Validations are performed on several publicly available databases as well as data provided by manufacturers of some commercially available fundus imaging devices. The segmentation and classification performance is assessed against expert clinician annotations in terms of sensitivity, specificity, accuracy, Jaccard, and Dice similarity indices. The results show that RDR based automated glaucoma assessment is about 8% to 10% more accurate than a cup-to-disc ratio (CDR) based system. An ablation study carried out considering the ground-truth expert outlines alone for classification showed that RDR is superior to CDR by 5.28% in a two-stage classification and about 3.21% in a three-stage severity grading.
Novel CMKLR1 Inhibitors for Application in Demyelinating Disease
Authors: Kumar Vineet , LaJevic Melissa , Pandrala Mallesh , Jacobo Sam A. , Malhotra Sanjay V. , Zabel Brian A. 
Published: May 2019

AbstractSmall molecules that disrupt leukocyte trafficking have proven effective in treating patients with multiple sclerosis (MS). We previously reported that chemerin receptor chemokine-like receptor 1 (CMKLR1) is required for maximal clinical and histological experimental autoimmune encephalomyelitis (EAE); and identified CMKLR1 small molecule antagonist 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) that significantly suppressed disease onset in vivo. Here we directly compared α-NETA versus FDA-approved MS drug Tecfidera for clinical efficacy in EAE; characterized key safety/toxicity parameters for α-NETA; identified structure-activity relationships among α-NETA domains and CMKLR1 inhibition; and evaluated improved α-NETA analogs for in vivo efficacy. α-NETA proved safe and superior to Tecfidera in suppressing clinical EAE. In addition, we discovered structurally differentiated α-NETA analogs (primarily ortho- or para-methoxy substitutions) with significantly improved target potency in vitro and improved efficacy in vivo. These findings suggest that α-NETA-based CMKLR1 inhibitors may prove safe and effective in treating demyelinating diseases and potentially other autoimmune disorders.
Reconstruction of larval origins based on genetic relatedness and biophysical modeling
Authors: Segura-García I. , Garavelli L. , Tringali M. , Matthews T. , Chérubin L. M. , Hunt J. , Box S. J. 
Published: May 2019

AbstractThe assessment of the mechanisms and patterns of larval connectivity between geographically separated populations leads to a better understanding of benthic marine population dynamics, especially in commercially valuable species. This study investigated for the first time the fine-scale temporal genetic variability of new settlers and their origins in a benthic marine organism with one of the longest pelagic larval phases, the Caribbean spiny lobster (Panulirus argus). We genotyped newly settled postlarvae in the Florida Keys and adults of spiny lobster from the Florida Keys and throughout the Caribbean Sea. We identified strong larval connectivity between Dominican Republic, Belize, Nicaragua, the Florida Keys, and West-Florida. The larval dispersal modeling suggests that Florida’s lobster population could receive recruits from within and from other areas outside its state and national maritime boundaries. The genetic analyses refine the oceanographic model indicating that the connectivity patterns described could also result from unknown parental populations sourcing adults and postlarvae in different spawning seasons to the Florida Keys. We discuss the importance of small temporal scales to identify patterns in larval export. Our findings are significant on two levels. From the larval dispersal perspective, genetic results and biophysical modeling identify patterns of gene flow enhancing persistence of local populations. From an economic and fishery perspective, P. argus is the most important commercial species in the Caribbean and our results inform how considering larval source and sink dynamics across international boundaries could improve management plans at local, national, and regional levels.
The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish
Authors: Stanic Karen , Reig German , Figueroa Ricardo J. , Retamal Pedro A. , Wichmann Ignacio A. , Opazo Juan C. , Owen Gareth I. , Corvalán Alejandro H. , Concha Miguel L. , Amigo Julio D. 
Published: May 2019

AbstractThe Reprimo gene family comprises a group of single-exon genes for which their physiological function remains poorly understood. Heretofore, mammalian Reprimo (RPRM) has been described as a putative p53-dependent tumor suppressor gene that functions at the G2/M cell cycle checkpoint. Another family member, Reprimo-like (RPRML), has not yet an established role in physiology or pathology. Importantly, RPRML expression pattern is conserved between zebrafish and human species. Here, using CRISPR-Cas9 and antisense morpholino oligonucleotides, we disrupt the expression of rprml in zebrafish and demonstrate that its loss leads to impaired definitive hematopoiesis. The formation of hemangioblasts and the primitive wave of hematopoiesis occur normally in absence of rprml. Later in development there is a significant reduction in erythroid-myeloid precursors (EMP) at the posterior blood island (PBI) and a significant decline of definitive hematopoietic stem/progenitor cells (HSPCs). Furthermore, loss of rprml also increases the activity of caspase-3 in endothelial cells within the caudal hematopoietic tissue (CHT), the first perivascular niche where HSPCs reside during zebrafish embryonic development. Herein, we report an essential role for rprml during hematovascular development in zebrafish embryos, specifically during the definitive waves of hematopoiesis, indicating for the first time a physiological role for the rprml gene.
Symptom trajectories in patients with panic disorder in a primary care intervention: Results from a randomized controlled trial (PARADISE)
Authors: Lukaschek Karoline , Hiller Thomas S. , Schumacher Ulrike , Teismann Tobias , Breitbart Jörg , Brettschneider Christian , König Hans-Helmut , Margraf Jürgen , Gensichen Jochen 
Published: May 2019

AbstractThis analysis aims to identify and characterize symptom trajectories in primary care patients with panic disorder with/without agoraphobia (PD/AG) who participated in a primary care team based training involving elements of cognitive behavioural therapy (CBT). Growth Mixture Modeling was used to identify different latent classes of change in patients with PD/AG (N = 176) who underwent treatment including CBT elements. We identified three patient classes with distinct similar trajectories. Class 1 (n = 58, mean age: 46.2 years ± 13.4 years, 81% women) consisted of patients with an initially high symptom burden, but symptoms declined constantly over the intervention period. Symptoms of patients in class 2 (n = 89, mean age: 44.2 years ± 14.5 years, 67.4% women) declined rapidly at the beginning, then patients went into a plateau-phase. The third class (n = 29, mean age: 47.0 years ± 12.4 years, 65.5% women) was characterized by an unstable course and had the worse outcome. Our findings show that only a minority did not respond to the treatment. To identify this minority and refer to a specialist would help patients to get intensive care in time.
Key nutritional factors and interactions during larval development of pikeperch (Sander lucioperca)
Authors: El Kertaoui Najlae , Lund Ivar , Assogba Hospice , Domínguez David , Izquierdo Maria S. , Baekelandt Sébastien , Cornet Valérie , Mandiki Syaghalirwa N. M. , Montero Daniel , Kestemont Patrick 
Published: May 2019

AbstractThe effects of 8 nutritional variables (Ca/P, Eicosapentaenoic acid (20:5n-3) + Docosahexaenoic acid (22:6n − 3) (EPA + DHA), Arachidonic acid (20:4n − 6) (ARA), Se, vitamins E, C, D and A) were investigated to identify their respective importance and interactions in pikeperch larval development. In this respect, two modalities (low and high levels) of each variable were tested through a fractional factorial experimental design allowing a reduction from 256 (28) to 16 (28 – 4) experimental units. Survival was significantly higher in larvae fed a high Ca/P diet while larval growth was significantly lower in larvae fed the same diet variant, associated with a higher incidence of kyphosis and pectoral anomalies in these larvae. Lordosis and scoliosis seemed to be mostly affected by dietary long chain polyunsaturated fatty acids (LC-PUFAs). A significant interaction was shown between n-3 LC-PUFA and vitamin C on jaw anomalies, while myocyte-specific enhancer factor 2C (mef2c) gene expression correlated positively with dietary vitamin C increment. Results also demonstrated an effect of the different nutrients and their interactions on the activity levels of digestive enzymatic activities. The results of the present study highlight the importance of the interactions between Ca/P, LC-PUFAs and vitamins C and E, suggesting their essential roles as key nutritional factors influencing pikeperch larval development.