bluuebunny/crossref_metadata_2025_split huggingface dataset:
Original association of ion transporters mediates the ECM-induced breast cancer cell survival: Kv10.1-Orai1-SPCA2 partnership
Authors: Peretti Marta , Badaoui Mehdi , Girault Alban , Van Gulick Laurence , Mabille Marie-Pierre , Tebbakha Riad , Sevestre Henri , Morjani Hamid , Ouadid-Ahidouch Halima 
Published: February 2019

AbstractIn the last years it has been shown that many components of tumor microenvironment (TM) can induce cell signaling that permit to breast cancer cells (BC) to maintain their aggressiveness. Ion channels have a role in mediating TM signal; recently we have demonstrated a functional collaboration between Kv10.1 and Orai1 channels in mediating the pro-survival effect of collagen 1 on BC cells. Here we show how SPCA2 (Secretory Pathway Ca2+ ATPase) has a role in this process and is able to support survival and proliferation induced by collagen 1. By participating to an auto-sustaining loop, SPCA2 enhances membrane expression of Kv10.1 and Orai1; the activity of every component of this trio is necessary to mediate a store independent calcium entry (SICE). This SICE is fundamental to maintain both the activation of the pro-survival pathway and the membrane localization and consequently the activity of the two channels. Moreover, the three proteins and the collagen receptor DDR1 are overexpressed only in aggressive tumors tissues. In this work, we propose a novel association between SPCA2, Kv10.1 and Orai1 involved in mediating transduction signals from TM to the BC cells that can be potentially exploited in the search of novel therapeutic targets specific to tumor tissues.
Mass Effect Deformation Heterogeneity (MEDH) on Gadolinium-contrast T1-weighted MRI is associated with decreased survival in patients with right cerebral hemisphere Glioblastoma: A feasibility study
Authors: Prasanna Prateek , Mitra Jhimli , Beig Niha , Nayate Ameya , Patel Jay , Ghose Soumya , Thawani Rajat , Partovi Sasan , Madabhushi Anant , Tiwari Pallavi 
Published: February 2019

AbstractSubtle tissue deformations caused by mass-effect in Glioblastoma (GBM) are often not visually evident, and may cause neurological deficits, impacting survival. Radiomic features provide sub-visual quantitative measures to uncover disease characteristics. We present a new radiomic feature to capture mass effect-induced deformations in the brain on Gadolinium-contrast (Gd-C) T1w-MRI, and their impact on survival. Our rationale is that larger variations in deformation within functionally eloquent areas of the contralateral hemisphere are likely related to decreased survival. Displacements in the cortical and subcortical structures were measured by aligning the Gd-C T1w-MRI to a healthy atlas. The variance of deformation magnitudes was measured and defined as Mass Effect Deformation Heterogeneity (MEDH) within the brain structures. MEDH values were then correlated with overall-survival of 89 subjects on the discovery cohort, with tumors on the right (n = 41) and left (n = 48) cerebral hemispheres, and evaluated on a hold-out cohort (n = 49 subjects). On both cohorts, decreased survival time was found to be associated with increased MEDH in areas of language comprehension, social cognition, visual perception, emotion, somato-sensory, cognitive and motor-control functions, particularly in the memory areas in the left-hemisphere. Our results suggest that higher MEDH in functionally eloquent areas of the left-hemisphere due to GBM in the right-hemisphere may be associated with poor-survival.
The oncological safety in minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis
Authors: Yang Du-Jiang , Xiong Jun-Jie , Lu Hui-Min , Wei Yi , Zhang Ling , Lu Shan , Hu Wei-Ming 
Published: February 2019

AbstractThe safety of minimally invasive distal pancreatectomy (MIDP) and open distal pancreatectomy (ODP) regarding oncological outcomes of pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. Therefore, the aim of this study was to examine the oncological safety of MIDP and ODP for PDAC. Major databases including PubMed, Embase, Science Citation Index Expanded, and the Cochrane Library were searched for studies comparing outcomes in patients undergoing MIDP and ODP for PDAC from January 1994 to August 2018. In total, 11 retrospective comparative studies with 4829 patients (MIDP: 1076, ODP: 3753) were included. The primary outcome was long-term survival, including 3-year overall survival (OS) and 5-year OS. The 3-year OS (hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.89, 1.21; P = 0.66) and 5-year OS (HR: 0.91, 95% CI: 0.65, 1.28; P = 0.59) showed no significant differences between the two groups. Furthermore, the positive surgical margin rate (weighted mean difference (WMD): 0.71, 95% CI: 0.56, 0.89, P = 0.003) was lower in the MIDP group. However, patients in the MIDP group had less intraoperative blood loss (WMD: −250.03, 95% CI: −359.68, −140.39; P < 0.00001), a shorter hospital stay (WMD: −2.76, 95% CI: −3.73, −1.78; P < 0.00001) and lower morbidity (OR: 0.57, 95% CI: 0.46, 0.71; P < 0.00001) and mortality (OR: 0.50, 95% CI: 0.31, 0.81, P = 0.005) than patients in the ODP group. The limited evidence suggested that MIDP might be safer with regard to oncological outcomes in PDAC patients. Therefore, future high-quality studies are needed to examine the oncological safety of MIDP.
Compton-based prompt gamma imaging using ordered origin ensemble algorithm with resolution recovery in proton therapy
Authors: Yao Zhiyang , Xiao Yongshun , Chen Zhiqiang , Wang Bo , Hou Qinhan 
Published: February 2019

AbstractPrompt gamma ray (PG) imaging based on Compton camera (CC) is promising to realize in vivo verification during the proton therapy. However, the finite spatial and energy resolution of current CC, as well as the Doppler broaden effect, degrade the quality and resolution of PG images. In addition, due to the inherent geometrical complexity of Compton camera data, PG imaging can be time-consuming and difficult to reconstruct in real-time, while using standard techniques such as filtered back-projection or maximum likelihood-expectation maximization. In this paper, we propose three modifications of origin ensembles with resolution recovery (OE-RR) algorithm based on Markov chains to accelerate the convergence to equilibrium of OE-RR algorithm and improve the image quality. For evaluation, we performed a Monte Carlo simulation of a three-stage CZT Compton camera with resolution loss to detect the PG produced by a proton beam in a water phantom, and evaluate image quality of the gamma rays emitted during proton irradiation. The results show that our ordered OE-RR algorithm realized a good resolution recovery and accurate estimation of the position, including the peak and the distal falloff of the PG emission with remarkably faster reconstruction, thus demonstrating the feasibility of this new method in non-idealized PG-based proton range verification.
The Placental Transcriptome in Late Gestational Hypoxia Resulting in Murine Intrauterine Growth Restriction Parallels Increased Risk of Adult Cardiometabolic Disease
Authors: Chu Alison , Casero David , Thamotharan Shanthie , Wadehra Madhuri , Cosi Amy , Devaskar Sherin U. 
Published: February 2019

AbstractIntrauterine growth restriction (IUGR) enhances risk for adult onset cardiovascular disease (CVD). The mechanisms underlying IUGR are poorly understood, though inadequate blood flow and oxygen/nutrient provision are considered common endpoints. Based on evidence in humans linking IUGR to adult CVD, we hypothesized that in murine pregnancy, maternal late gestational hypoxia (LG-H) exposure resulting in IUGR would result in (1) placental transcriptome changes linked to risk for later CVD, and 2) adult phenotypes of CVD in the IUGR offspring. After subjecting pregnant mice to hypoxia (10.5% oxygen) from gestational day (GD) 14.5 to 18.5, we undertook RNA sequencing from GD19 placentas. Functional analysis suggested multiple changes in structural and functional genes important for placental health and function, with maximal dysregulation involving vascular and nutrient transport pathways. Concordantly, a ~10% decrease in birthweights and ~30% decrease in litter size was observed, supportive of placental insufficiency. We also found that the LG-H IUGR offspring exhibit increased risk for CVD at 4 months of age, manifesting as hypertension, increased abdominal fat, elevated leptin and total cholesterol concentrations. In summary, this animal model of IUGR links the placental transcriptional response to the stressor of gestational hypoxia to increased risk of developing cardiometabolic disease.
Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity
Authors: Manzo Giorgia , Ferguson Philip M. , Gustilo V. Benjamin , Hind Charlotte K. , Clifford Melanie , Bui Tam T. , Drake Alex F. , Atkinson R. Andrew , Sutton J. Mark , Batoni Giovanna , Lorenz Christian D. , Phoenix David A. , Mason A. James 
Published: February 2019

AbstractAntimicrobial peptides (AMPs) are a potential source of new molecules to counter the increase in antimicrobial resistant infections but a better understanding of their properties is required to understand their native function and for effective translation as therapeutics. Details of the mechanism of their interaction with the bacterial plasma membrane are desired since damage or penetration of this structure is considered essential for AMPs activity. Relatively modest modifications to AMPs primary sequence can induce substantial changes in potency and/or spectrum of activity but, hitherto, have not been predicted to substantially alter the mechanism of interaction with the bacterial plasma membrane. Here we use a combination of molecular dynamics simulations, circular dichroism, solid-state NMR and patch clamp to investigate the extent to which temporin B and its analogues can be distinguished both in vitro and in silico on the basis of their interactions with model membranes. Enhancing the hydrophobicity of the N-terminus and cationicity of the C-terminus in temporin B improves its membrane activity and potency against both Gram-negative and Gram-positive bacteria. In contrast, enhancing the cationicity of the N-terminus abrogates its ability to trigger channel conductance and renders it ineffective against Gram-positive bacteria while nevertheless enhancing its potency against Escherichia coli. Our findings suggest even closely related AMPs may target the same bacterium with fundamentally differing mechanisms of action.
Electrospun patterned porous scaffolds for the support of ovarian follicles growth: a feasibility study
Authors: Liverani Liliana , Raffel Nathalie , Fattahi Amir , Preis Alexander , Hoffmann Inge , Boccaccini Aldo R. , Beckmann Matthias W. , Dittrich Ralf 
Published: February 2019

AbstractRecently, the interest of the scientific community is focused on the application of tissue engineering approach for the fertility restoration. In this paper innovative patterned electrospun fibrous scaffolds were fabricated and used as 3D system for porcine follicles culture. The obtained scaffolds demonstrated to be a suitable support which did not alter or interfere with the typical spherical follicles morphology. The fibrillar structure of the scaffolds mimics the morphology of the healthy native tissue. The use of porcine follicles implied many advantages respect to the use of mouse model. Relevant results showed that more than the scaffold pattern and struts dimension, the selection of proper biomaterials improve the follicles adhesion and development.
A continuous fluorescence assay for simple quantification of bile salt hydrolase activity in the gut microbiome
Authors: Brandvold Kristoffer R. , Weaver Jacqueline M. , Whidbey Christopher , Wright Aaron T. 
Published: February 2019

AbstractThe microbiota of the mammalian gut plays a dynamic role in controlling host physiology. The effect of gut microbiota activity on host health is particularly evident in the case of bile homeostasis. Bile is produced by the host and is modified by the gut microbiota, which impacts the net hydrophobicity of the total bile acid pool, and also modulates host signaling pathways. A key mechanism by which the microbiota modify bile is through deconjugation of bile salts through bile salt hydrolase (BSH) enzymatic activity, which is postulated to be a prerequisite for all further microbial metabolism. BSH activity in the gut is largely considered to be beneficial for the host, and genes encoding BSHs are found in the genomes of many taxa found in over-the-counter probiotics. Despite the therapeutic relevance of this enzyme, there is no sensitive and simple assay for continuous monitoring of BSH activity, and there are no non-destructive means of characterizing its activity in whole cell or microbial community samples. Herein, we describe a continuous fluorescence assay that can be used for characterization of BSH activity with purified protein, cell lysates, whole cells, and in human gut microbiome samples. The method is a “turn-on” reporter strategy, which employs synthetic substrates that yield a fluorescent product upon BSH-dependent turnover. This assay is used to show the first in vivo characterization of BSH activity. We also demonstrate continuous, non-destructive quantification of BSH activity in a human fecal microbiome sample containing recombinant BSH.
Determination of basal phosphodiesterase activity in mouse rod photoreceptors with cGMP clamp
Authors: Turunen Teemu T. , Koskelainen Ari 
Published: February 2019

AbstractLight regulates cGMP concentration in the photoreceptor cytoplasm by activating phosphodiesterase (PDE) molecules through a G-protein signalling cascade. Spontaneous PDE activity is present in rod outer segments even in darkness. This basal PDE activity (βdark) has not been determined in wild type mammalian photoreceptor cells although it plays a key role in setting the sensitivity and recovery kinetics of rod responses. We present a novel method for determination of βdark using local electroretinography (LERG) from isolated mouse retinas. The method is based on the ability of PDE inhibitors to decrease βdark, which can be counterbalanced by increasing PDE activity with light. This procedure clamps cytoplasmic cGMP to its dark value. βdark can be calculated based on the amount of light needed for the “cGMP clamp” and information extracted from the registered rod photoresponses. Here we apply this method to determine βdark values for the first time in the mammalian rods and obtain the following estimates for different mouse models: 3.9 s−1 for wild type, 4.5 s−1 for guanylate cyclase activating proteins (GCAPs) knockout, and 4.4 s−1 for GCAPs and recoverin double knockout mice. Our results suggest that depletion of GCAPs or recoverin do not affect βdark.
Observation of Restored Topological Surface States in Magnetically Doped Topological Insulator
Authors: Kim Jinsu , Shin Eun-Ha , Sharma Manoj K. , Ihm Kyuwook , Dugerjav Otgonbayar , Hwang Chanyong , Lee Hwangho , Ko Kyung-Tae , Park Jae-Hoon , Kim Miyoung , Kim Hanchul , Jung Myung-Hwa 
Published: February 2019

AbstractThe introduction of ferromagnetic order in topological insulators in general breaks the time-reversal symmetry and a gap is opened in topological surface bands. Various studies have focused on gap-opened magnetic topological insulators, because such modified band structures provide a promising platform for observing exotic quantum physics. However, the role of antiferromagnetic order in topological insulators is still controversial. In this report, we demonstrate that it is possible to restore the topological surface states by effectively reducing the antiferromagnetic ordering in Gd-substituted Bi2Te3. We successfully control the magnetic impurities via thermal treatments in ultra-high vacuum condition and observe apparent restoration of topological surface band dispersions. The microscopic mechanism of atomic rearrangements and the restoration process of topological surface states are unraveled by the combination of scanning tunneling microscopy measurements and density functional theory calculations. This work provides an effective way to control the magnetic impurities which is strongly correlated with topological surface states.
Nanoparticle-mediated magnetic hyperthermia is an effective method for killing the human-infective protozoan parasite Leishmania mexicana in vitro
Authors: Berry Sarah L. , Walker Karen , Hoskins Clare , Telling Neil D. , Price Helen P. 
Published: January 2019

AbstractCutaneous leishmaniasis is a neglected tropical disease characterized by disfiguring skin lesions. Current chemotherapeutic options depend on toxic, expensive drugs that are both difficult to administer and becoming less effective due to increasing levels of resistance. In comparison, thermotherapy displays greater patient compliance and less adverse systemic effects, but there are still significant issues associated with this. The procedure is painful, requiring local anaesthetic, and is less effective against large lesions. Using nanoparticles to controllably generate heat in a localized manner may provide an alternative solution. Here we evaluate magnetic hyperthermia, using iron oxide magnetic nanoparticles, as a localized, heat-based method to kill the human-infective parasite in vitro. We assessed the effectiveness of this method against the differentiated, amastigote form of the parasite using three distinct viability assays: PrestoBlue, Live/Dead stain and a novel luciferase-based assay. Changes in amastigote morphology and ultrastructure were assessed by immunofluorescence, scanning and transmission electron microscopy. Our findings show that magnetic hyperthermia is an effective method to kill host-infective amastigotes, with morphological changes consistent with heat treatment. This method has the potential to be a step-change for research into new therapeutic options that moves away from the expensive chemotherapeutics currently dominating the research climate.
Acidogenesis, solventogenesis, metabolic stress response and life cycle changes in Clostridium beijerinckii NRRL B-598 at the transcriptomic level
Authors: Patakova Petra , Branska Barbora , Sedlar Karel , Vasylkivska Maryna , Jureckova Katerina , Kolek Jan , Koscova Pavlina , Provaznik Ivo 
Published: February 2019

AbstractClostridium beijerinckii NRRL B-598 is a sporulating, butanol and hydrogen producing strain that utilizes carbohydrates by the acetone-butanol-ethanol (ABE) fermentative pathway. The pathway consists of two metabolic phases, acidogenesis and solventogenesis, from which the latter one can be coupled with sporulation. Thorough transcriptomic profiling during a complete life cycle and both metabolic phases completed with flow cytometry, microscopy and a metabolites analysis helped to find out key genes involved in particular cellular events. The description of genes/operons that are closely involved in metabolism or the cell cycle is a necessary condition for metabolic engineering of the strain and will be valuable for all C. beijerinckii strains and other Clostridial species. The study focused on glucose transport and catabolism, hydrogen formation, metabolic stress response, binary fission, motility/chemotaxis and sporulation, which resulted in the composition of the unique image reflecting clostridial population changes. Surprisingly, the main change in expression of individual genes was coupled with the sporulation start and not with the transition from acidogenic to solventogenic metabolism. As expected, solvents formation started at pH decrease and the accumulation of butyric and acetic acids in the cultivation medium.
The Dissociable Effects of Induced Positive and Negative Moods on Cognitive Flexibility
Authors: Hsieh Shulan , Lin Siang Jyun 
Published: February 2019

AbstractThis study investigates how different valences of induced moods modulate cognitive flexibility in a task-switching paradigm. Forty-eight participants aged 19–25 years performed task switching after watching emotional film clips to induce an emotion (neutral, positive, or negative emotions). Two indicators of flexibility were evaluated: (1) the performance decrement reflected by increased reaction time (RT) or errors on the task-switch trial relative to a task-repetition trial, which is known as the “switching cost,” and (2) the performance improvement reflected by decreased RT or errors when switching from a task-switching context to a single-task context, which is known as the “fade-out” effect. These indicators reflect cognitive flexibility on short and long time scales, respectively. The results show that negative moods reduced switching costs, particularly in incongruent trials. In addition, negative moods were found to cause a prolonged fade-out effect compared with neutral and positive moods, indicating that participants required more trials to adjust to the single-task condition after experiencing the task-switching context. The result suggests that only negative moods and not positive moods modulated both the short and long time scales of cognitive flexibility but with dissociable effects. Possible explanations are discussed.
Identification and characterization of synthetic chondroitin-4-sulfate binding peptides in neuronal functions
Authors: Loers Gabriele , Liao Yonghong , Hu Chengliang , Xue Weikang , Shen Huifan , Zhao Weijiang , Schachner Melitta 
Published: January 2019

AbstractChondroitin sulfate proteoglycans (CSPGs), up-regulated in and around the glial scar after mammalian spinal cord injury, have been suggested to be key inhibitory molecules for functional recovery by impeding axonal regrowth/sprouting and synaptic rearrangements. CSPG-mediated inhibition is mainly associated with the glycosaminoglycan chains of CSPGs, and chondroitin-4-sulfate (C4S) is the predominant sulfated structure that regulates axonal guidance and growth in the adult nervous system. With the aim to find molecules that neutralize the inhibitory functions of C4S, we screened a phage display library for peptides binding to C4S. From the phage clones binding to C4S we selected three peptides for further analysis. We observed that these peptides bind to C4S, but not chondroitin-6-sulfate, heparin sulfate or dermatan sulfate, in a concentration-dependent and saturable manner, whereas the scrambled peptides showed highly reduced or no binding to C4S. The C4S-binding peptides, but not their scrambled counterparts, when added to cultures of mouse cerebellar neurons and human neuroblastoma cells, neutralized the inhibitory functions of the C4S- and CSPG-coated substrate on cell adhesion, neuronal migration and neurite outgrowth. These results indicate that the C4S-binding peptides neutralize several inhibitory functions of CSPGs, suggesting that they may be beneficial in repairing mammalian nervous system injuries.