bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience
Authors: Hix Jeremy M.L. , Mallett Christiane L. , Latourette Matthew , Munoz Kirk A. , Shapiro Erik M. 
Published: February 2020

AbstractPigs are an important translational research model for biomedical imaging studies, and especially for modeling diseases of the liver. Dynamic contrast enhanced (DCE)-MRI is experimentally used to measure liver function in humans, but has never been characterized in pig liver. Here we performed DCE-MRI of pig liver following the delivery of two FDA approved hepato-specific MRI contrast agents, Gd-EOB-DTPA (Eovist) and Gd-BOPTA (Multihance), and the non-hepatospecific agent Magnevist, and optimized the anesthesia and animal handling protocol to acquire robust data. A single pig underwent 5 scanning sessions over six weeks, each time injected at clinical dosing either with Eovist (twice), Multihance (twice) or Magnevist (once). DCE-MRI was performed at 1.5T for 60 minutes. DCE-MRI showed rapid hepatic MRI signal enhancement following IV injection of Eovist or Multihance. Efflux of contrast agent from liver exhibited kinetics similar to that in humans, except for one hyperthermic animal where efflux was very fast. As expected, Magnevist was non-enhancing in the liver. The hepatic signal enhancement from Eovist matched that seen in humans and primates, while the hepatic signal enhancement from Multihance was different, similar to rodents and dogs, likely the result of differential hepatic organic anion transport polypeptides. This first experience with these agents in pigs provides valuable information on contrast agent dynamics in normal pig liver. Given the disparity in contrast agent uptake kinetics with humans for Multihance, Eovist should be used in porcine models for biomedical imaging. Proper animal health maintenance, especially temperature, seems essential for accurate and reproducible results.
Plasmon-Coupled Photocapacitor Neuromodulators
Authors: Melikov Rustamzhon , Srivastava Shashi Bhushan , Karatum Onuralp , Dogru Itir Bakis , Jalali Houman Bahmani , Sadeghi Sadra , Dikbas Ugur Meric , Ulgut Burak , Kavakli Ibrahim Halil , Nizamoglu Sedat 
Published: February 2020

AbstractEfficient transduction of optical energy to bioelectrical stimuli is an important goal for effective communication with biological systems. For that plasmonics has significant potential via boosting the light-matter interactions. However, plasmonics has been primarily used for heat-induced cell stimulation due to membrane capacitance change (i.e., optocapacitance). Instead, here we demonstrate that plasmonic coupling to photocapacitor biointerfaces improves safe and efficacious neuromodulating displacement charges for an average of 185% in the entire visible spectrum while maintaining the Faradaic currents below 1%. Hot-electron injection dominantly leads the enhancement of displacement current at blue spectral window, and nanoantenna effect is mainly responsible for the improvement at red-spectral region. The plasmonic photocapacitor facilitates wireless modulation of single cells at 3-orders of magnitude below the maximum retinal intensity levels corresponding to one of the most sensitive optoelectronic neural interfaces. This study introduces a new way of using plasmonics for safe and effective photostimulation of neurons and paves the way toward ultra-sensitive plasmon-assisted neurostimulation devices.
Altered GABAergic inhibition in CA1 pyramidal neurons modifies despair-like behavior in mice
Authors: Yoon Sang Ho , Chung Geehoon , Song Woo Seok , Oh Sung Pyo , Kim Jeongjin , Kim Sang Jeong , Kim Myoung-Hwan 
Published: February 2020

AbstractDespair is a common human feeling characterized by the loss of hope and is a core symptom of depressive disorders. However, little is known regarding neural circuits mediating despair and their modulation by antidepressants. Here we show that alterations in inhibitory synaptic transmission in the hippocampus affect behavioral despair in mice. Reduced interneuron density, knockdown of GABAAreceptor gamma 2 subunit gene (Gabrg2) or DREADD-mediated suppression of interneuron activity resulted in disinhibition of CA1 neurons and anti-despair-like behaviors in mice. Similarly, a low dose of pentylenetetrazol, a GABAAR antagonist, induced transient anti-despair-like behaviors, with rapid eukaryotic elongation factor 2 (eEF2) activation in the hippocampus. Conversely, pharmacological and chemogenetic potentiation of GABAergic transmission in CA1 neurons induced despair-like behaviors. The antidepressant ketamine rapidly increased c-Fos expression in CA1 neurons and induced anti-despair-like behaviors. These results suggest that the enhanced hippocampal CA1 neuron activity induces anti-despair-like behaviors and contributes to the antidepressant effects of ketamine.
The construction and application of a new 17-plex Y-STR system using universal fluorescent PCR
Authors: Liu Jinding , Wang Rongshuai , Shi Jie , Cheng Xiaojuan , Hao Ting , Guo Jiangling , Wang Jiaqi , Liu Zidong , Li Wenyan , Fan Haoliang , Yun Keming , Yan Jiangwei , Zhang Gengqian 
Published: February 2020

AbstractY-chromosomal short tandem repeat (Y-STR) polymorphisms are useful in forensic identification, population genetics and human structures. However, the current Y-STR systems are limited in discriminating distant relatives in a family with a low discrimination power. Increasing the capacity of detecting Y chromosomal polymorphisms will drastically narrow down the matching number of genealogy populations or pedigrees. In this study, we developed a system containing 17 Y-STRs that are complementary to the current commercially available Y-STR kits. This system was constructed by multiplex PCR with expected sizes of 126-400 bp labeled by different fluorescence molecules (DYS715, DYS709, DYS716, DYS713 and DYS607 labeled by FAM; DYS718, DYS723, DYS708 and DYS714 labeled by JOE; DYS712, DYS717, DYS721 and DYS605 labeled by TAMRA; and DYS719, DYS726, DYS598 and DYS722 labeled by ROX). The system was extensively tested for sensitivity, male specificity, species specificity, mixture, population genetics and mutation rates following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. The genetic data were obtained from eight populations with a total of 1260 individuals. Our results showed that all the 17 Y-STRs are human- and male-specific and include only one copy of the Y-chromosome. The 17 Y-STR system detects 143 alleles and has a high discrimination power (0.996031746). Mutation rates were different among the 17 Y-STRs, ranging from 0.30% to 3.03%. In conclusion, our study provides a robust, sensitive and cost-effective genotyping method for human identification, which will be beneficial for narrowing the search scope when applied to genealogy searching with the Y-STR DNA databank.
Epigenetic transcriptional reprogramming by WT1 mediates a repair response during podocyte injury
Authors: Ettou Sandrine , Jung Youngsook L. , Miyoshi Tomoya , Jain Dhawal , Hiratsuka Ken , Schumacher Valerie , Taglienti Mary E. , Morizane Ryuji , Park Peter J. , Kreidberg Jordan A. 
Published: February 2020

ABSTRACTIn the context of human disease, the mechanisms whereby transcription factors reprogram gene expression in response to injury are not well understood. This is particularly true in kidney podocytes, injury to which is the common and initial event in many processes that lead End Stage Kidney Disease. WT1 is a master regulator of gene expression in podocytes, binding nearly all genes known to be crucial for maintenance of the glomerular filtration barrier. Here, using purified populations of podocytes and glomeruli, we investigated WT1-mediated transcriptional reprogramming during the course of podocyte injury. Using the Adriamycin murine model of Focal Segmental Glomerulosclerosis, we discovered that podocyte injury led to increased intensity of WT1 binding and to the acquisition of new WT1 binding sites, both at previously identified target genes and at newly bound target genes, providing mechanistic insight on the transcriptional response to injury. We also observed a previously unrecognized transient increase in expression of WT1 target genes in both mice and human kidney organoids. Together, these features appear to constitute an attempt to repair the glomerular filtration barrier after podocyte injury. At later stages of injury, when proteinuria became severe, there was greatly decreased WT1 binding to most target genes. Furthermore, WT1 appeared to be required to maintain active chromatin marks at its target genes. These active marks were converted to repressive marks after loss of WT1 or Adriamycin-induced injury. This response to injury suggests that there may be a potential window of opportunity for repairing podocyte injury as a treatment for glomerular disease in humans.
Non-invasive real-time imaging of reactive oxygen species (ROS) using multispectral auto-fluorescence imaging technique: a novel tool for redox biology
Authors: Habibalahi Abbas , Moghari Mahdieh Dashtbani , Campbell Jared M. , Anwer Ayad G. , Mahbub Saabah B. , Gosnell Martin , Saad Sonia , Pollock Carol , Goldys Ewa M. 
Published: February 2020

AbstractDetecting reactive oxygen species (ROS) that play a critical role as redox modulators and signalling molecules in biological systems currently requires invasive methods such as ROS - specific indicators for imaging and quantification. We developed a non-invasive, real-time, label-free imaging technique for assessing the level of ROS in live cells and thawed cryopreserved tissues that is compatible within-vivoimaging. The technique is based on autofluorescence multispectral imaging (AFMI) carried out in an adapted fluorescence microscope with an expanded number of spectral channels spanning specific excitation (365 nm-495 nm) and emission (420 nm-700 nm) wavelength ranges. We established a strong quantitative correlation between the spectral information obtained from AFMI and the level of ROS obtained from CellROX staining. The results were obtained in several cell types (HeLa, PANC1 and mesenchymal stem cells) and in live kidney tissue. Additioanly, two spectral regimes were considered: with and without UV excitation (wavelengths > 400 nm); the latter being suitable for UV-sensitive systems such as the eye. Data were analyzed by linear regression combined with an optimization method of swarm intelligence. This allowed the calibration of AFMI signals to the level of ROS with excellent correlation (R= 0.84, p=0.00) in the entire spectral range and very good correlation (R= 0.78, p=0.00) in the limited, UV-free spectral range. We also developed a strong classifier which allowed us to distinguish moderate and high levels of ROS in these two regimes (AUC= 0.91 in the entire spectral range and AUC = 0.78 for UV-free imaging). These results indicate that ROS in cells and tissues can be imaged non-invasively, which opens the way to future clinical applications in conditions where reactive oxygen species are known to contribute to progressive disease such as in ophthalmology, diabetes, kidney disease, cancer and neurodegenerative diseases.
Fe(III) heme sets an activation threshold for processing distinct groups of pri-miRNAs in mammalian cells
Authors: Weitz Sara H. , Quick-Cleveland Jen , Jacob Jose P. , Barr Ian , Senturia Rachel , Koyano Kikuye , Xiao Xinshu , Weiss Shimon , Guo Feng 
Published: February 2020

ABSTRACTThe essential biological cofactor heme is synthesized in cells in the Fe(II) form. Oxidized Fe(III) heme is specifically required for processing primary transcripts of microRNAs (pri-miRNAs) by the RNA-binding protein DGCR8, a core component of the Microprocessor complex. It is unknown how readily available Fe(III) heme is in the largely reducing environment in human cells and how changes in cellular Fe(III) heme availability alter microRNA (miRNA) expression. Here we address the first question by characterizing DGCR8 mutants with various degrees of deficiency in heme-binding. We observed a strikingly simple correlation between Fe(III) heme affinityin vitroand the Microprocessor activity in HeLa cells, with the heme affinity threshold for activation estimated to be between 0.6-5 pM under typical cell culture conditions. The threshold is strongly influenced by cellular heme synthesis and uptake. We suggest that the threshold reflects a labile Fe(III) heme pool in cells. Based on our understanding of DGCR8 mutants, we reanalyzed recently reported miRNA sequencing data and conclude that heme is generally required for processing canonical pri-miRNAs, that heme modulates the specificity of Microprocessor, and that cellular heme level and differential DGCR8 heme occupancy alter the expression of distinct groups of miRNAs in a hierarchical fashion. Overall, our study provides the first glimpse of a labile Fe(III) heme pool important for a fundamental physiological function and reveal principles governing how Fe(III) heme modulates miRNA maturation at a genomic scale. We also discuss potential states and biological significance of the labile Fe(III) heme pool.
Striatal direct and indirect pathway neurons differentially control the encoding and updating of goal-directed learning
Authors: Peak James , Chieng Billy , Hart Genevra , Balleine Bernard W. 
Published: February 2020

SummaryThe posterior dorsomedial striatum (pDMS) is necessary for goal-directed action, however the role of the direct (dSPN) and indirect (iSPN) spiny projection neurons in the pDMS in such action remains unclear. In this series of experiments, we examined the role of pDMS SPNs in goal-directed action and found that, whereas dSPNs were critical for goal-directed learning and for energizing the learned response, iSPNs were involved in updating that learning to support response flexibility. Instrumental training elevated expression of the plasticity marker Zif268 in dSPNs only, and chemogenetic suppression of dSPN activity during training prevented goal-directed learning. Unilateral optogenetic inhibition of dSPNs induced an ipsilateral response bias in goal-directed action performance. In contrast, although initial goal-directed learning was unaffected by iSPN manipulations, optogenetic inhibition of iSPNs, but not dSPNs, impaired the updating of this learning and attenuated response flexibility after changes in the action-outcome contingency.
Localized activation of ependymal progenitors induces EMT-mediated glial bridging after spinal cord injury
Authors: Zhou Lili , Burris Brooke , Mcadow Ryan , Mokalled Mayssa H. 
Published: February 2020

ABSTRACTUnlike mammals, adult zebrafish undergo spontaneous recovery after major spinal cord injury. Whereas scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue to facilitate regeneration. Here, we performed FACS sorting and genome-wide profiling to determine the transcriptional identity of purified bridging glia. We found that Yap-Ctgf signaling activates epithelial to mesenchymal transition (EMT) in localized niches of ependymal cells to promote glial bridging and regeneration. Preferentially activated in early bridging glia, Yap is required for the expression of the glial bridging factor Ctgfa and for functional spinal cord repair. Ctgfa regulation is controlled by an injury responsive enhancer element that drives expression in early bridging glia after injury. Yap-Ctgf signaling activates a mesenchymal transcriptional program that drives glial bridging. This study revealed the molecular signatures of bridging glia and identified an injury responsive gene regulatory network that promotes spinal cord regeneration in zebrafish.
Differential Host Gene Signatures in Response toMycobacterium tuberculosisInfection
Authors: Tazi Loubna , Wang Ping , Fornage Myriam 
Published: February 2020

ABSTRACTTuberculosis (TB) represents a global public health threat and is the leading cause of morbidity and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug resistance. Yet, there is still a fundamental gap in understanding the complex and dynamic interactions between differentMycobacterium tuberculosisstrains and the host. In this project, we investigated the host immune response to differentM. tuberculosisstrains, including avirulent or virulent and rifampin-resistant or isoniazid-resistant strains in THP-1 cells. We identified major differences in the gene response profiles in response to infection with these strains. The expression of IDO1 and IL-1β in the infected cells was stronger in all virulentM. tuberculosisstrains. The most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells infected with the isoniazid-resistant strain, compared to the rifampin-drug resistant strain and the drug-sensitive strain. A transcription regulation analysis of the differentially expressed genes in infected THP-1 cells implicated two major transcription factors, NF-κB and STAT1. The differentially expressed ISGs in response to the isoniazid-resistantM. tuberculosisstrain were associated with STAT1 signaling, while the expression of many cytokines, such IL-1β, was associated with NF-κB signaling. Our data suggest that the isoniazid-resistantM. tuberculosisstrain preferentially activates STAT1 in response to cGAS-STING activation and induces a host immune response signature that is characteristic of isoniazid resistance. This study has a potential to provide important new insights into TB pathogenesis and to characterize host gene signatures specifically involved in isoniazid-resistant TB.
Inositol synthesis gene is required for circadian rhythm ofDrosophila melanogastermating behavior
Authors: Sakata Kazuki , Kawasaki Haruhisa , Ishida Norio 
Published: February 2020

AbstractAccumulating evidence indicates that the molecular circadian clock underlies the mating behavior ofDrosophila melanogaster.However, information about which gene affects circadian mating behavior is poorly understood in animals. The present study found that feedingMyo-inositol enhanced the close-proximity (CP) rhythm ofD. melanogastermating behavior and lengthened the period of the CP rhythm. Then, to understand a role for inositol synthesis to fly mating behavior, we established theInos(Myo-inositol 1-phosphate synthase)geneknock down fly strains with RNAi. Interestingly, the CP behavior of this three-different driver knock down strains was arrhythmic, but the locomotor rhythm was rhythmic. The data of three-differentInosknock down strains suggests thatInosgene expression of upper LNd, l-LNV, 5ths-LNvin brain is necessary for proper CP rhythm generation inD. melanogaster. The data indicated that theInosgene is involved in the role for the circadian rhythm ofD. melanogastermating behavior.
Bent DNA bows as amplifiers and biosensors for detecting DNA-interacting salts and molecules
Authors: Freeland Jack , Zhang Lihua , Wang Shih-Ting , Ruiz Mason , Wang Yong 
Published: February 2020

AbstractDue to the central role of DNA, its interactions with inorganic salts and small organic molecules are important for understanding various fundamental cellular processes in living systems, deciphering the mechanism of many diseases related to DNA damages, and discovering or designing inhibitors and drugs targeting DNA. However, there is still a need for improved sensitivity to detect these interactions, especially in situations where expensive sophisticated equipment is not available. Here we report our development and demonstration of bent DNA bows for amplifying, sensing, and detecting the interactions of 14 inorganic salts and small organic molecules with DNA. With the bent DNA bows, these interactions were easily visualized and quantified in gel electrophoresis, which were difficult to measure without bending. In addition, the strength of the interactions of DNA with the various salts/molecules were quantified using the modified Hill equation. This work highlights the amplification effects of the bending elastic energy stored in the DNA bows and the potential use of the DNA bows for quantitatively measuring DNA interactions with small molecules as simple economic methods; it may also pave the way for exploiting the bent DNA bows for other applications such as monitoring water quality and screening DNA-targeting molecules and drugs.
Differential TM4SF5-mediated SIRT1 modulation and signaling for chronic liver disease
Authors: Ryu Jihye , Kim Eunmi , Kang Min-Kyung , Song Dae-Geun , Shin Eun-Ae , Jung Jae Woo , Nam Seo Hee , Kim Ji Eon , Kim Hye-Jin , Lee Jeong-Hoon , Yoon Jung-Hwan , Son Taekwon , Kim Semi , Kim Hwi Young , Lee Jung Weon 
Published: February 2020

AbstractHere we show the roles of transmembrane 4 L six family member 5 (TM4SF5) in the progression of nonalcoholic steatosis (or NAFL) to steatohepatitis (NASH). The overexpression of TM4SF5 caused nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and livers exhibited lipid accumulation, decreased SIRT1, increased SREBPs levels, and inactive STAT3 via SOCS1/3 upregulation. In older animals, TM4SF5 under an inflammatory environment increased SIRT1 expression and STAT3 activity with no significant change to SOCSs and SREBPs levels, leading to active STAT3-mediated fibrotic extracellular matrix (ECM) production. Liver tissues from clinical human patients with NAFL or NASH also showed such a TM4SF5-SIRT1-STAT3-ECM relationship correlated with fibrosis score and age. Ligand-independent and TM4SF5-mediated STAT3 activity led to collagen I and laminins/laminin γ2 expression in hepatic stellate cells and hepatocytes, respectively. Laminin γ2 suppression abolished CCl4-mediated liver damage and ECM production and reduced SIRT1 and active-STAT3, but did not alter SREBP1 or SOCSs levels. These findings suggest that TM4SF5, CCL20, SIRT1, and/or laminin γ2 may be promising therapeutic targets against liver disease.
Antimicrobial silver inhibits bacterial movement and stalls flagellar motor
Authors: Russell Benjamin , Rogers Ariel , Kurilich Matthew , Krishnamurthi Venkata Rao , Chen Jingyi , Wang Yong 
Published: February 2020

AbstractSilver (Ag) has been gaining broad attention due to their antimicrobial activities and the increasing resistance of bacteria to commonly prescribed antibiotics. However, various aspects of the antimicrobial mechanism of Ag have not been understood, including how silver affects the motility of bacteria, a factor that is intimately related to bacterial virulence. Here we report our study on the antibiotic effects of Ag+ions on the motility ofE. colibacteria using swimming and tethering assays. We observed that the bacteria slowed down dramatically when subjected to Ag+ions, providing direct evidence showing that Ag inhibits the motility of bacteria. In addition, through tethering assays, we monitored the rotation of flagellar motors and observed that the tumbling frequency of bacteria increased significantly in the presence of Ag+ions. Furthermore, the rotation of bacteria in the tethering assays were analyzed using hidden Markov model (HMM); and we found that Ag+-treatment led to a significant decrease in the tumbling-to-running transition rate of the bacteria, suggesting that the rotation of bacterial flagellar motors was stalled by Ag+ions. This work provided a new quantitative understanding on the mechanism of Ag-based antimicrobial agents in bacterial motility.