bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory effect of two Trichinella spiralis serine protease inhibitors on the host’s immune system
Authors: Xu Jingyun , Yu Pengcheng , Wu Lijia , Liu Mingxu , Lu Yixin 
Published: November 2019

AbstractTrichinella spiralis (T. spiralis) is widely distributed throughout the world and can cause serious zoonotic parasitic diseases. Serine protease inhibitors (SPIs) have unique enzyme inhibitory activity and occupy an important position in the interaction between parasites and hosts. In order to further understand the immunoprotective effect of SPIs on T. spiralis invasion in vivo, the Kazal and Serpin type SPI of T. spiralis (TsKaSPI and TsAdSPI) were mixed with Freund’s adjuvant in equal volume to immunize mice. The results showed that the expression of IgG1 and IgG2a in serum, the proliferation of spleen cells, and the expression level of cytokines were all increased. The results of flow cytometry showed that the expression of CD4+CD25+Foxp3+ Tregs, CD8+CD28− T cells, CD19+CD5+CD1dhi Bregs in spleen were also increased. Therefore, both TsKaSPI and TsAdSPI could induce strong humoral and cellular immune responses. And the results of adult reduction rate and pathological changes of intestine after adult invasion also indicated that both TsKaSPI and TsAdSPI could prevent T. spiralis from invading intestine. To explore the regulatory effects of TsKaSPI and TsAdSPI on the immune function of macrophage, the results of ELISA showed that the expression of cytokines in cell supernatant were increased. And the results of Western blot showed that both TsKaSPI and TsAdSPI could induce phosphorylation of JAK2 and STAT3 receptors, thereby affecting the signal transduction of macrophages. This experiment demonstrated that SPIs could act as effector molecules affecting the immune function of host when infected with T. spiralis.
Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli
Authors: Rojas-Lopez Maricarmen , Martinelli Manuele , Brandi Valentina , Jubelin Grégory , Polticelli Fabio , Soriani Marco , Pizza Mariagrazia , Desvaux Mickaël , Rosini Roberto 
Published: November 2019

AbstractEnterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.
Functional and structural basis of E. coli enolase inhibition by SF2312: a mimic of the carbanion intermediate
Authors: Krucinska Jolanta , Lombardo Michael N. , Erlandsen Heidi , Hazeen Akram , Duay Searle S. , Pattis Jason G. , Robinson Victoria L. , May Eric R. , Wright Dennis L. 
Published: November 2019

AbstractMany years ago, the natural secondary metabolite SF2312, produced by the actinomycete Micromonospora, was reported to display broad spectrum antibacterial properties against both Gram-positive and Gram-negative bacteria. Recent studies have revealed that SF2312, a natural phosphonic acid, functions as a potent inhibitor of human enolase. The mechanism of SF2312 inhibition of bacterial enolase and its role in bacterial growth and reproduction, however, have remained elusive. In this work, we detail a structural analysis of E. coli enolase bound to both SF2312 and its oxidized imide-form. Our studies support a model in which SF2312 acts as an analog of a high energy intermediate formed during the catalytic process. Biochemical, biophysical, computational and kinetic characterization of these compounds confirm that altering features characteristic of a putative carbanion (enolate) intermediate significantly reduces the potency of enzyme inhibition. When SF2312 is combined with fosfomycin in the presence of glucose-6 phosphate, significant synergy is observed. This suggests the two agents could be used as a potent combination, targeting distinct cellular mechanism for the treatment of bacterial infections. Together, our studies rationalize the structure-activity relationships for these phosphonates and validate enolase as a promising target for antibiotic discovery.
Field cress genome mapping: Integrating linkage and comparative maps with cytogenetic analysis for rDNA carrying chromosomes
Authors: Desta Zeratsion Abera , Kolano Bozena , Shamim Zeeshan , Armstrong Susan J. , Rewers Monika , Sliwinska Elwira , Kushwaha Sandeep Kumar , Parkin Isobel A. P. , Ortiz Rodomiro , de Koning Dirk-Jan 
Published: November 2019

AbstractField cress (Lepidium campestreL.), despite its potential as a sustainable alternative oilseed plant, has been underutilized, and no prior attempts to characterize the genome at the genetic or molecular cytogenetic level have been conducted. Genetic maps are the foundation for anchoring and orienting annotated genome assemblies and positional cloning of candidate genes. Our principal goal was to construct a genetic map using integrated approaches of genetic, comparative and cytogenetic map analyses. In total, 503 F2interspecific hybrid individuals were genotyped using 7,624 single nucleotide polymorphism markers. Comparative analysis demonstrated that ~57% of the sequenced loci inL. campestrewere congruent withArabidopsis thaliana(L.) genome and suggested a novel karyotype, which predates the ancestral crucifer karyotype. Aceto-orcein chromosome staining and fluorescencein situhybridization (FISH) analyses confirmed thatL. campestre,L. heterophyllumBenth. and their hybrids had a chromosome number of 2n = 2x = 16. Flow cytometric analysis revealed that both species possess 2C roughly 0.4 picogram DNA. Integrating linkage and comparative maps with cytogenetic map analyses assigned two linkage groups to their particular chromosomes. Future work could incorporate FISH utilizingA. thalianamapped BAC clones to allow the chromosomes of field cress to be identified reliably.
Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab
Authors: Funazo Tomoko Yamamoto , Nomizo Takashi , Ozasa Hiroaki , Tsuji Takahiro , Yasuda Yuto , Yoshida Hironori , Sakamori Yuichi , Nagai Hiroki , Hirai Toyohiro , Kim Young Hak 
Published: November 2019

AbstractNivolumab improves the prognosis of non-small cell lung cancer (NSCLC) but can cause immune-related adverse events (irAEs). Reports have indicated longer progression-free survivals (PFSs) in patients with irAEs than in those without irAEs. We reported associations between programmed death ligand-1 (PD-L1) single nucleotide polymorphisms (SNPs) and PFS after nivolumab treatment. We hypothesized that adverse events might be associated with the SNPs of PD-L1. We analyzed data from 111 patients with NSCLC treated with nivolumab. The response rate was 14%, and the median PFS was 68 days. We found patients with the adverse event of low free tetraiodothyronine (fT4) had significantly longer PFSs than those without low fT4 (not reached vs 67 days; hazard ratio [HR], 0.297; P = 0.010). Moreover, median overall survival was longer in patients with low fT4 than those without low fT4 (not reached vs 556 days, HR, 0.139; P = 0.020). Patients with the T allele of rs1411262 (P = 0.0073) and with the A allele of rs822339 (P = 0.0204) developed low fT4. Patients with the T/T genotype had longer PFSs than with those with the C/T and C/C genotypes of rs1411262 (165 vs. 67 days, HR, 1.65; P = 0.040), and those with the A/A genotype had longer PFSs than those with the A/G and G/G genotypes of rs822339 (182 vs. 67 days, HR, 1.76; P = 0.025). In the patients with advanced NSCLC, low fT4 after nivolumab treatment was associated with significantly longer PFSs. The SNPs of PD-L1 may be associated with the adverse events of nivolumab.
Monolayer MoS2 field effect transistor with low Schottky barrier height with ferromagnetic metal contacts
Authors: Gupta Sachin , Rortais F. , Ohshima R. , Ando Y. , Endo T. , Miyata Y. , Shiraishi M. 
Published: November 2019

AbstractTwo-dimensional MoS2 has emerged as promising material for nanoelectronics and spintronics due to its exotic properties. However, high contact resistance at metal semiconductor MoS2 interface still remains an open issue. Here, we report electronic properties of field effect transistor devices using monolayer MoS2 channels and permalloy (Py) as ferromagnetic (FM) metal contacts. Monolayer MoS2 channels were directly grown on SiO2/Si substrate via chemical vapor deposition technique. The increase in current with back gate voltage (Vg) shows the tunability of FET characteristics. The Schottky barrier height (SBH) estimated for Py/MoS2 contacts is found to be +28.8 meV (at Vg = 0V), which is the smallest value reported so-far for any direct metal (magnetic or non-magnetic)/monolayer MoS2 contact. With the application of positive gate voltage, SBH shows a reduction, which reveals ohmic behavior of Py/MoS2 contacts. Low SBH with controlled ohmic nature of FM contacts is a primary requirement for MoS2 based spintronics and therefore using directly grown MoS2 channels in the present study can pave a path towards high performance devices for large scale applications.
Continuation of tropical Pacific Ocean temperature trend may weaken extreme El Niño and its linkage to the Southern Annular Mode
Authors: Lim Eun-Pa , Hendon Harry H. , Hope Pandora , Chung Christine , Delage Francois , McPhaden Michael J. 
Published: November 2019

AbstractObservational records show that occurrences of the negative polarity of the Southern Annular Mode (low SAM) is significantly linked to El Niño during austral spring and summer, potentially providing long-lead predictability of the SAM and its associated surface climate conditions. In this study, we explore how this linkage may change under a scenario of a continuation of the ocean temperature trends that have been observed over the past 60 years, which are plausibly forced by increasing greenhouse gas concentrations. We generated coupled model seasonal forecasts for three recent extreme El Niño events by initialising the forecasts with observed ocean anomalies of 1 September 1982, 1997 and 2015 added into (1) the current ocean mean state and into (2) the ocean mean state updated to include double the recent ocean temperature trends. We show that the strength of extreme El Niño is reduced with the warmer ocean mean state as a result of reduced thermocline feedback and weakened rainfall-wind-sea surface temperature coupling over the tropical eastern Pacific. The El Niño-low SAM relationship also weakens, implying the possibility of reduced long-lead predictability of the SAM and associated surface climate impacts in the future.
The burden of submicroscopic and asymptomatic malaria in India revealed from epidemiology studies at three varied transmission sites in India
Authors: van Eijk Anna Maria , Sutton Patrick L. , Ramanathapuram Lalitha , Sullivan Steven A. , Kanagaraj Deena , Priya G. Sri Lakshmi , Ravishankaran Sangamithra , Asokan Aswin , Sangeetha V. , Rao Pavitra N. , Wassmer Samuel C. , Tandel Nikunj , Patel Ankita , Desai Nisha , Choubey Sandhya , Ali Syed Zeeshan , Barla Punam , Oraon Rajashri Rani , Mohanty Stuti , Mishra Shobhna , Kale Sonal , Bandyopadhyay Nabamita , Mallick Prashant K. , Huck Jonathan , Valecha Neena , Singh Om P. , Pradhan K. , Singh Ranvir , Sharma S. K. , Srivastava Harish C. , Carlton Jane M. , Eapen Alex 
Published: November 2019

AbstractMalaria in India, while decreasing, remains a serious public health problem, and the contribution of submicroscopic and asymptomatic infections to its persistence is poorly understood. We conducted community surveys and clinic studies at three sites in India differing in their eco-epidemiologies: Chennai (Tamil Nadu), Nadiad (Gujarat), and Rourkela (Odisha), during 2012–2015. A total of 6,645 subject blood samples were collected for Plasmodium diagnosis by microscopy and PCR, and an extensive clinical questionnaire completed. Malaria prevalence ranged from 3–8% by PCR in community surveys (24 infections in Chennai, 56 in Nadiad, 101 in Rourkela), with Plasmodium vivax dominating in Chennai (70.8%) and Nadiad (67.9%), and Plasmodium falciparum in Rourkela (77.3%). A proportional high burden of asymptomatic and submicroscopic infections was detected in community surveys in Chennai (71% and 71%, respectively, 17 infections for both) and Rourkela (64% and 31%, 65 and 31 infections, respectively). In clinic studies, a proportional high burden of infections was identified as submicroscopic in Rourkela (45%, 42 infections) and Chennai (19%, 42 infections). In the community surveys, anemia and fever were significantly more common among microscopic than submicroscopic infections. Exploratory spatial analysis identified a number of potential malaria hotspots at all three sites. There is a considerable burden of submicroscopic and asymptomatic malaria in malarious regions in India, which may act as a reservoir with implications for malaria elimination strategies.
Chaperone Sigma1R mediates the neuroprotective action of afobazole in the 6-OHDA model of Parkinson’s disease
Authors: Voronin Mikhail V. , Kadnikov Ilya A. , Voronkov Dmitry N. , Seredenin Sergey B. 
Published: November 2019

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disease with limited treatment options. Therefore, the identification of therapeutic targets is urgently needed. Previous studies have shown that the ligand activation of the sigma-1 chaperone (Sigma1R) promotes neuroprotection. The multitarget drug afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) was shown to interact with Sigma1Rs and prevent decreases in striatal dopamine in the 6-hydroxydopamine (6-OHDA)-induced parkinsonism model. The aim of the present study was to elucidate the role of Sigma1Rs in afobazole pharmacological activity. Using ICR mice we found that administration of afobazole (2.5 mg/kg, i.p.) or selective agonist of Sigma1R PRE-084 (1.0 mg/kg, i.p.) over 14 days normalizes motor disfunction and prevents decreases in dopamine in the 6-OHDA-lesioned striatum. Afobazole administration also prevents the loss of TH + neurons in the substantia nigra. The pre-administration of selective Sigma1R antagonist BD-1047 (3.0 mg/kg, i.p.) abolishes the activity of either afobazole or PRE-084, as determined using the rotarod test and the analysis of striatal dopamine content. The current study demonstrates the contribution of Sigma1Rs in the neuroprotective effect of afobazole in the 6-OHDA model of Parkinson’s disease and defines the therapeutic perspective of Sigma1R agonists in the clinic.
Inferring correlations associated to causal interactions in brain signals using autoregressive models
Authors: López-Madrona Víctor J. , Matias Fernanda S. , Mirasso Claudio R. , Canals Santiago , Pereda Ernesto 
Published: November 2019

AbstractThe specific connectivity of a neuronal network is reflected in the dynamics of the signals recorded on its nodes. The analysis of how the activity in one node predicts the behaviour of another gives the directionality in their relationship. However, each node is composed of many different elements which define the properties of the links. For instance, excitatory and inhibitory neuronal subtypes determine the functionality of the connection. Classic indexes such as the Granger causality (GC) quantifies these interactions, but they do not infer into the mechanism behind them. Here, we introduce an extension of the well-known GC that analyses the correlation associated to the specific influence that a transmitter node has over the receiver. This way, the G-causal link has a positive or negative effect if the predicted activity follows directly or inversely, respectively, the dynamics of the sender. The method is validated in a neuronal population model, testing the paradigm that excitatory and inhibitory neurons have a differential effect in the connectivity. Our approach correctly infers the positive or negative coupling produced by different types of neurons. Our results suggest that the proposed approach provides additional information on the characterization of G-causal connections, which is potentially relevant when it comes to understanding interactions in the brain circuits.
Gold-Hybridized Zinc Oxide Nanorods as Real-Time Low-Cost NanoBiosensors for Detection of virulent DNA signature of HPV-16 in Cervical Carcinoma
Authors: Ramesh Thevendran , Foo Kai Loong , R. Haarindraprasad , Sam Annie Jeyachristy , Solayappan Maheswaran 
Published: November 2019

AbstractDetection of host integrated viral oncogenes are critical for early and point-of-care molecular diagnostics of virus-induced carcinoma. However, available diagnostic approaches are incapable of combining both cost-efficient medical diagnosis and high analytical performances. To circumvent this, we have developed an improved IDE-based nanobiosensor for biorecognition of HPV-16 infected cervical cancer cells through electrochemical impedance spectroscopy. The system is fabricated by coating gold (Au) doped zinc oxide (ZnO) nanorods interfaced with HPV-16 viral DNA bioreceptors on top of the Interdigitated Electrode (IDE) chips surface. Due to the concurrently improved sensitivity and biocompatibility of the designed nanohybrid film, Au decorated ZnO-Nanorod biosensors demonstrate exceptional detection of HPV-16 E6 oncogene, the cancer biomarker for HPV infected cervical cancers. This sensor displayed high levels of sensitivity by detecting as low as 1fM of viral E6 gene target. The sensor also exhibited a stable functional life span of more than 5 weeks, good reproducibility and high discriminatory properties against HPV-16. Sensor current responses are obtained from cultured cervical cancer cells which are close to clinical cancer samples. Hence, the developed sensor is an adaptable tool with high potential for clinical diagnosis especially useful for economically challenged countries/regions.
Fanconi anemia proteins counteract the implementation of the oncogene-induced senescence program
Authors: Helbling-Leclerc Anne , Dessarps-Freichey Françoise , Evrard Caroline , Rosselli Filippo 
Published: November 2019

AbstractFanconi Anemia (FA), due to the loss-of-function of the proteins that constitute the FANC pathway involved in DNA replication and genetic stability maintainance, is a rare genetic disease featuring bone marrow failure, developmental abnormalities and cancer predisposition. Similar clinical stigmas have also been associated with alterations in the senescence program, which is activated in physiological or stress situations, including the unscheduled, chronic, activation of an oncogene (oncogene induced senescence, OIS). Here, we wanted to determine the crosstalk, if any, between the FANC pathway and the OIS process. OIS was analyzed in two known cellular models, IMR90-hTERT/ER:RASG12V and WI38-hTERT/ER:GFP:RAF1, harboring 4-hydroxytamoxifen-inducible oncogenes. We observed that oncogene activation induces a transitory increase of both FANCA and FANCD2 as well as FANCD2 monoubiquitination, readout of FANC pathway activation, followed by their degradation. FANCD2 depletion, which leads to a pre-senescent phenotype, anticipates OIS progression. Coherently, FANCD2 overexpression or inhibition of its proteosomal-dependent degradation slightly delays OIS progression. The pro-senescence protease cathepsin L, which activation is anticipated during OIS in FANCD2-depleted cells, also participates to FANCD2 degradation. Our results demonstrate that oncogene activation is first associated with FANCD2 induction and activation, which may support initial cell proliferation, followed by its degradation/downregulation when OIS proceeds.
The effect of Substance P/Heparin conjugated PLCL polymer coating of bioinert ePTFE vascular grafts on the recruitment of both ECs and SMCs for accelerated regeneration
Authors: Kim Donghak , Chung Justin J. , Jung Youngmee , Kim Soo Hyun 
Published: November 2019

AbstractArtificial vascular grafts consisting of ePTFE have been mainly used in clinics for the treatment of cardiovascular disease. However, artificial grafts can become clogged after a long time due to thrombosis, as graft maturation by endothelialization is limited. The strategy introduced in this study is to induce graft remodeling through interaction between the bioinert graft and the body. The Substance P (SP) and heparin were covalently conjugated with PLCL, an elastic biocompatible copolymer and the Substance P-conjugated PLCL (SP-PLCL) and/or heparin-conjugated PLCL (Hep-PLCL) were vacuum-coated onto ePTFE vascular grafts. To assess the effectiveness of the coating, coated samples were evaluated by implanting them subcutaneously into SD-Rats. Coatings allow grafts to be remodeled by creating a microenvironment where cells can grow by infiltrating into the grafts while also greatly enhancing angiogenesis. In particular, a double coating of Hep-PLCL and SP-PLCL (Hep/SP-PLCL) at four weeks showed markedly improved vascular remodeling through the recruitment of mesenchymal stem cells (MSCs), vascular cells (ECs, SMCs) and M2 macrophages. Based on these results, it is expected that when the Hep/SP-PLCL-coated ePTFE vascular grafts are implantedin situ, long-term patency will be assured due to the appropriate formation of an endothelial layer and smooth muscle cells in the grafts like native vessels.
Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions
Authors: Han Kyung Ah , Kim Jinhu , Kim Hyeonho , Kim Dongwook , Lim Dongseok , Ko Jaewon , Um Ji Won 
Published: November 2019

AbstractMembers of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons.