bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAPAS: A Thresholding Approach for Probability Map Automatic Segmentation in Multiple Sclerosis
Authors: Valcarcel Alessandra M. , Muschelli John , Pham Dzung L. , Martin Melissa Lynne , Yushkevich Paul , Calabresi Peter A. , Bakshi Rohit , Shinohara Russell T. 
Published: April 2019

AbstractTotal brain white matter lesion (WML) volume is the most widely established magnetic resonance imaging (MRI) outcome measure in studies of multiple sclerosis (MS). To estimate WML volume, there are a number of automatic segmentation methods, yet, manual delineation remains the gold standard approach. These approaches often yield a probability map to which a threshold is applied to create lesion segmentation masks. Unfortunately, few approaches systematically determine the threshold employed; many methods use a manually selected threshold, thus introducing human error and bias into the automated procedure. In this study, we propose and validate an automatic thresholding algorithm, Thresholding Approach for Probability Map Automatic Segmentation in Multiple Sclerosis (TAPAS), to obtain subject-specific threshold estimates for probability map automatic segmentation of T2-weighted (T2) hyperintense WMLs. Using multimodal MRI, the proposed method applies an automatic segmentation algorithm to obtain probability maps. We obtain the true subject-specific threshold that maximizes Sørensen-Dice Similarity Coefficient (DSC). Then the subject-specific thresholds are modeled on a naive estimate of volume using a general additive model. Applying this model, we predict a subject-specific threshold in data not used for training. We ran a Monte Carlo-resampled split-sample cross-validation (100 validation sets) using two data sets: the first obtained from the Johns Hopkins Hospital (JHH) on a Philips 3 Tesla (3T) scanner (n = 94) and a second collected at the Brigham and Women’s Hospital (BWH) using a Siemens 3T scanner (n = 40). By means of the proposed automated technique, in the JHH data, we found an average reduction in subject-level absolute error of 0.1 mL per one mL increase in manual volume. Using Bland-Altman analysis, we found that volumetric bias associated with group-level thresholding is mitigated when applying TAPAS. The BWH data showed similar absolute error estimates using group-level thresholding or TAPAS likely since Bland-Altman analyses indicate no systematic biases associated with group or TAPAS volume estimates. The current study presents the first validated fully automated method for subject-specific threshold prediction to segment brain lesions.
Quantitative proteomics identifies novel PIAS1 substrates involved in cell migration and motility
Authors: Li Chongyang , McManus Francis P. , Plutoni Cédric , Pascariu Cristina Mirela , Nelson Trent , Delsin Lara Elis Alberici , Emery Gregory , Thibault Pierre 
Published: April 2019

ABSTRACTThe Protein Inhibitor of Activated STAT 1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways, including STAT signaling, p53 pathway, and the steroid hormone signaling pathway. PIAS1 can SUMOylate PML (at Lys-65 and Lys-160) and PML-RARα promoting their ubiquitin-mediated degradation. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. To understand the mechanism of action of PIAS1, we developed a quantitative SUMO proteomic approach to identify potential substrates of PIAS1 in a system-wide manner. Our analyses enabled the profiling of 983 SUMO sites on 544 proteins, of which 204 SUMO sites on 123 proteins were identified as putative PIAS1 substrates. These substrates are involved in different cellular processes, such as transcriptional regulation, DNA binding and cytoskeleton dynamics. Further functional studies on Vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, revealed that PIAS1 exerts its effects on cell migration and cell invasion through the SUMOylation of VIM at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly, and cells expressing a non-SUMOylatable VIM mutant showed reduced levels of proliferation and migration. Our approach not only provides a novel strategy for the identification of E3 SUMO ligase substrates, but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.
Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core
Authors: Deroche Marion A. , Lassalle Olivier , Manzoni Olivier J. 
Published: April 2019

ABSTRACTThe nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs and feedforward inhibition that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). Feedforward inhibition of MSN firing too, was input and cell-type specific: while minimal at vHipp-D1 and vHipp-D2 inputs; it inhibited with similar efficacy BLA-D1 or BLA-D2 inputs, was minimal at PFC-D1 but maximal at PFC-D2 inputs. We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, while CB1 receptors (CB1R) uniformly depress excitatory pathways irrespective of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity.SIGNIFICANCE STATEMENTWe examined the impact of connections from the ventral hippocampus (vHipp,) basolateral amygdala (BLA) and prefrontal cortex (PFC) onto identified medium spiny neurons (MSN) in the adult accumbens core. We found BLA inputs were strongest at D1 MSNs while PFC inputs dominate D2 MSNs. We evaluated the role of the endocannabinoid system in pathway- and cell-specific plasticity and found that CB1 receptors (CB1R) and TRPV1 receptors (TRPV1R) bidirectionally control synaptic transmission and plasticity onto accumbens’ MSNs in a pathway- and cell-specific manner. Finally, we clarify how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses.
Preparation of PLGA Nanoparticles Encapsulated with Fluorescent Probe Coumarin-6
Authors: Purr Elizebeth , Marshall Jacob , Smith John 
Published: April 2019

AbstractIn this report, we provided a novel platform to prepare fluorescent probe coumarin-6 nanoparticles by using biodegradable material polylactic acid-glycolic acid copolymer (PLGA) as material. The coumarin-6-PLGA nanoparticles were prepared by double emulsion and solvent evaporation. The encapsulation efficiency and releasing kinetics were also investigated. Results indicate that the encapsulation efficiency of coumarin-6 nanoparticles was 51.6%, the utilization rate was 81.9%, the average particle size was 135 nm, and the leakage rate of coumarin-6 in vitro was lower than 72 h. 2%. Our experimental results provide evidence that PLGA nanoparticles can effectively encapsulate fluorescent probe Coumarin-6 and release the probe in a controlled manner.
IMAGE: High-powered detection of genetic effects on DNA methylation using integrated methylation QTL mapping and allele-specific analysis
Authors: Fan Yue , Vilgalys Tauras P. , Sun Shiquan , Peng Qinke , Tung Jenny , Zhou Xiang 
Published: April 2019

AbstractIdentifying genetic variants that are associated with methylation variation – an analysis commonly referred to as methylation quantitative trait locus (mQTL) mapping -- is important for understanding the epigenetic mechanisms underlying genotype-trait associations. Here, we develop a statistical method, IMAGE, for mQTL mapping in sequencing-based methylation studies. IMAGE properly accounts for the count nature of bisulfite sequencing data and incorporates allele-specific methylation patterns from heterozygous individuals to enable more powerful mQTL discovery. We compare IMAGE with existing approaches through extensive simulation. We also apply IMAGE to analyze two bisulfite sequencing studies, in which IMAGE identifies more mQTL than existing approaches.
Rho-kinase planar polarisation at tissue boundaries depends on phospho-regulation of membrane residence time
Authors: Sidor Clara , Stevens Tim J. , Jin Li , Boulanger Jérôme , Röper Katja 
Published: April 2019

SummaryRho-kinase (Rok) is a major myosin II activator during morphogenesis. In theDrosophilaembryonic salivary gland placode Rok is planar polarised at the tissue boundary, through a negative regulation by the apical polarity protein Crumbs that is anisotropically localised at the boundary. However, in inner cells of the placode both Crumbs and Rok are isotropically enriched at junctions. We propose a model that reconciles both behaviours through modulation of Rok membrane residence time by Crumbs and downstream effectors. Using FRAP in embryos expressing endogenously-tagged Rok combined within silicosimulations, we find that the lower membrane dissociation rate (koff) of Rok at the tissue boundary, where Crumbs membrane levels are lower, explains this boundary-specific effect. The S/T-kinase Pak1 negatively affects Rok membrane associationin vivowithin the epidermis, andin vitrocan phosphorylate Rok near the PH domain that mediates membrane association. Pak1 is recruited to the membrane by Cdc42 which, like its binding partner Crumbs, shows anisotropic localisation at the boundary. These data reveal an important mechanism of modulation of Rok membrane residence time via affecting the koffthat may be widely employed during tissue morphogenesis.
Phylogenomics of Selaginellaceae with special reference to the enigmatic sanguinolenta group
Authors: Zhang Hong-Rui , Wei Ran , Xiang Qiao-Ping , Zhang Xian-Chun 
Published: April 2019

AbstractSelaginellaceae has been repeatedly proved as monophyly by previous studies with only one genus being recognized. However, the subgeneric classification has been debated during the recent decades. Furthermore, phylogenetic position of the newly identified sanguinolenta group has not been resolved, varying depending on the datasets and analysis methods. We carried out the phylogenomic analyses of twenty-six species from Selaginellaceae with ten species being newly sequenced and three species representing the sanguinolenta group. Four of the ten newly sequenced plastomes are assembled into the complete molecules, whereas the other six species are only assembled into five to sixteen contigs owing to high numbers of repeats. The phylogenetic framework from our study is basically congruent with the subgeneric classification of Weststrand and Korall (2016b). The position of sanguinolenta group was resolved as the basal clade in subg. Stachygynandrum, which support the position β proposed by Weststrand and Korall (2016a), also supported by the morphological characters of dimorphic vegetative leaves, monomorphic sporophylls and intermixed sporangial arrangements. Both values of dS, dN and GC content in Selaginellaceae plastomes were significantly higher than those of other lycophytes (Isoetaceae and Lycopodiaceae). The correlation analysis showed that the elevated synonymous substitution rate was significantly correlated with the high GC content in Selaginellaceae. Besides, the values of dS and dN differs significantly between branches in the phylogenetic tree of Selaginellaceae. We propose that both high GC content and the extensive RNA editing sites contributed to the elevated substitution rate in Selaginellaceae, and all of these three factors could influence the stability of phylogenetic topology of Selaginellaceae.
Two Y chromosome-encoded genes determine sex in kiwifruit
Authors: Akagi Takashi , Pilkington Sarah M. , Varkonyi-Gasic Erika , Henry Isabelle M. , Sugano Shigeo S. , Sonoda Minori , Firl Alana , McNeilage Mark A. , Douglas Mikaela J. , Wang Tianchi , Rebstock Ria , Voogd Charlotte , Datson Paul , Allan Andrew C. , Beppu Kenji , Kataoka Ikuo , Tao Ryutaro 
Published: April 2019

ABSTRACTDioecy, the presence of male and female individuals, has evolved independently in multiple flowering plant lineages. Although theoretical models for the evolution of dioecy, such as the “two-mutation” model, are well established, little is known about the specific genes determining sex and their evolutionary history. Kiwifruit, a major tree crop consumed worldwide, is a dioecious species. In kiwifruit, we had previously identified a Y-encoded sex-determinant candidate gene acting as the suppressor of feminization (SuF), named Shy Girl (SyGI). Here, we identified a second Y-encoded sex-determinant that we named Friendly boy (FrBy), which exhibits strong expression in tapetal cells. Gene-editing and complementation analyses in Arabidopsis thaliana and Nicotiana tabacum indicated that FrBy acts for the maintenance of male (M) functions, independently of SyGI, and that these functions are conserved across angiosperm species. We further characterized the genomic architecture of the small (< 1 Mb) male specific region of the Y-chromosome (MSY), which harbors only two genes significantly expressed in developing gynoecia and androecia, respectively: SyGI and FrBy. Resequencing of the genome of a natural hermaphrodite kiwifruit revealed that this individual is genetically male but carries deletion(s) of parts of the Y-chromosome, including SyGI. Additionally, expression of FrBy in female kiwifruit resulted in hermaphrodite plants. These results clearly indicate that Y-encoded SyGI and FrBy act independently as the SuF and M factors in kiwifruit, respectively, and provide insight into the evolutionary path leading to a two-factor sex determination system but also a new breeding approach for dioecious species.
A genetic selection reveals functional metastable structures embedded in a toxin-encoding mRNA
Authors: Masachis Sara , Tourasse Nicolas J. , Lays Claire , Faucher Marion , Chabas Sandrine , Iost Isabelle , Darfeuille Fabien 
Published: April 2019

AbstractPost-transcriptional regulation plays important roles to finely tune gene expression in bacteria. In particular, regulation of type I toxin-antitoxin (TA) systems is achieved through sophisticated mechanisms involving toxin mRNA folding. Here, we set up a genetic approach to decipher the molecular underpinnings behind the regulation of a type I TA in Helicobacter pylori. We used the lethality induced by chromosomal inactivation of the antitoxin to select mutations that suppress toxicity. We found that single point mutations are sufficient to allow cell survival. Mutations located either in the 5’ untranslated region or within the open reading frame of the toxin hamper its translation by stabilizing stem-loop structures that sequester the Shine-Dalgarno sequence. We propose that these short hairpins correspond to metastable structures that are transiently formed during transcription to avoid premature toxin expression. This work uncovers the co-transcriptional inhibition of translation as an additional layer of TA regulation in bacteria.
Regenerative growth is constrained bybrain tumorto ensure proper patterning inDrosophila
Authors: Abidi Syeda Nayab Fatima , Hsu Felicity Ting-Yu , Smith-Bolton Rachel K. 
Published: April 2019

AbstractSome animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent overgrowth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in theDrosophilawing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.Author SummaryWhile much has been published about the signals that stimulate regeneration, the mechanisms that constrain and/or terminate regeneration have not been well characterized. Thus, we do not understand what limits may exist on the rate of regenerative growth, what mechanisms constrain regeneration, and what the consequences might be of enhancing regrowth. Here, we detail our discovery and characterization of a mechanism that constrains regeneration, and the deleterious effects of reducing that constraint. In this manuscript, we describe our identification of the RNA regulator Brat as a factor that constrains regenerative growth. Without this constraint on regenerative growth, patterning mistakes occur leading to a malformed regenerated structure. We demonstrate that the patterning errors are not due to faster growth itself, but are due to the overexpression of the pro-growth transcription factor Myc.
Decreased viability and neurite length in neural cells treated with chitosan-dextran sulfate nanocomplexes
Authors: Zamproni Laura N. , Teixeira Daniela , Alliegro Amanda Arnaut , Maugéri Ieda Longo , Rieux Anne des , Porcionatto Marimelia A. 
Published: April 2019

AbstractCXCL12 is a chemokine known to regulate migration, proliferation, and differentiation of neural stem cells (NSCs) and to play a neuroprotective role in ischemic stroke. Chitosan-dextran sulfate nanocomplexes (Ch/DS NC) are known nanoparticulated systems used to efficiently deliver heparin-binding factors. Here we evaluate Ch/DS NC as carriers for CXCL12 in a mouse model of stroke. Free CXCL12 reduced the size of the ischemic brain lesion. However, when Ch/DS NC were administrated, the stroke volume increased. Neurotoxic screening revealed that Ch/DS NC reduced neuronal viability, decreased the extension of neurites and impaired NSC migration in vitro. To the best of our knowledge, neurotoxicity of Ch/DS NC has not been reported and further screenings will be needed in order to evaluate the biological safety of these nanocomposites. Our results add new data on nanoparticle neurotoxicity and may help us to better understand the complex interactions of the nanostructures with biological components.
Zinc restriction promotes β-cell hyper-hormonemia and endocrine pancreas degeneration in mice
Authors: Sisnande Tháyna , Lima Cleverton K. , da Silva Dayana Cabral , Beninatto Thayana Moulin , Alves Natália Leão , Amaral Mariana J. , Miranda-Alves Leandro , Lima Luís Maurício T. R. 
Published: April 2019

AbstractZinc is a key component of proteins, including interaction with varying pancreatic hormones, including insulin and amylin. Zinc is key in insulin crystallinity in ZnT8 knock-out mice models, although the dietary role of zinc restriction over both energetic metabolism and ß-pancreatic hormonemia and morphology remained unexplored. We aimed to test whether dietary zinc restriction on swiss male mice would impact over endocrine pancreas and metabolic phenotype. We evaluated the role of dietary zinc restriction on ß-pancreatic hormonemia on non-transgenic Swiss male mice weaned onto a control or low-zinc diet for 4 weeks. Growth, glycemia, insulinemia, amylinemia and pancreatic islet were smaller in intervention group despite insulin crystallinity in secretory granules. We have found overlabelling for insulin, amylin and toxic oligomers in apoptotic pancreatic islet. High production of β-pancreatic hormones in zinc-restricted animals counteract the decreasing islet size due to their apoptotic cells. We conclude that zinc deficiency is sufficient to promote islet β-cell hormonal disruption and degeneration.
Can fallopian tube anatomy predict pregnancy and pregnancy outcomes after tubal reversal surgery?
Authors: de Souza Rafael S. , Berger Gary S. 
Published: April 2019

ABSTRACTWe conducted this study to determine if postoperative fallopian tube anatomy can predict the likelihood of pregnancy and pregnancy outcomes after tubal sterilisation reversal.We built a flexible, non-parametric, multivariate model via generalised additive models to assess the effects of these tubal parameters observed during tubal reparative surgery: tubal lengths; differences in tubal segment location and diameters at the anastomosis sites; and, fibrosis of the tubal muscularis.Age and tubal length (in that order) are the primary features determining the likelihood of pregnancy. For pregnancy outcomes, age is the primary predictor of miscarriage, but tubal length is the most influential predictor of the odds of birth and ectopic pregnancy. Segment location and diameters contribute slightly to the odds of miscarriage and ectopic pregnancy, whereas fibrosis has little apparent effect.This study is the first to show that a statistical learning predictive model based on fallopian tube anatomy can predict both pregnancy and pregnancy outcome probabilities after tubal reversal surgery.
Metabolic Perceptrons for Neural Computing in Biological Systems
Authors: Pandi Amir , Koch Mathilde , Voyvodic Peter L , Soudier Paul , Bonnet Jerome , Kushwaha Manish , Faulon Jean-Loup 
Published: April 2019

AbstractSynthetic biological circuits are promising tools for developing sophisticated systems for medical, industrial, and environmental applications. So far, circuit implementations commonly rely on gene expression regulation for information processing using digital logic. Here, we present a new approach for biological computation through metabolic circuits designed by computer-aided tools, implemented in both whole-cell and cell-free systems. We first combine metabolic transducers to build an analog adder, a device that sums up the concentrations of multiple input metabolites. Next, we build a weighted adder where the contributions of the different metabolites to the sum can be adjusted. Using a computational model trained on experimental data, we finally implement two four-input “perceptrons” for desired binary classification of metabolite combinations by applying model-predicted weights to the metabolic perceptron. The perceptron-mediated neural computing introduced here lays the groundwork for more advanced metabolic circuits for rapid and scalable multiplex sensing.