bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice
Authors: Mahmoud Motamed Elsayed , Fereig Ragab , Nishikawa Yoshifumi 
Published: January 2017

ABSTRACTToxoplasma gondiiis a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronicT. gondiiinfection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-γ) to anhedonic and despair-related behaviors inT. gondii-infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas inT. gondii-infected mice, treatment normalized kynurenine/tryptophan (Kyn/Trp) ratios in both plasma and brain tissue. Additionally,T. gondiiinfection failed to induce anhedonic and despair-like behaviors or increase the Kyn/Trp ratio in immunocompromised (IFN-γ−/−) mice, whereas sickness behavior was observed in both immunocompetent and IFN-γ−/−mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn/Trp ratios inT. gondii-infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection withT. gondiiresulted in IFN-γ production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors.
Significance of a Posttranslational Modification of the PilA Protein of Geobacter sulfurreducens for Surface Attachment, Biofilm Formation, and Growth on Insoluble Extracellular Electron Acceptors
Authors: Richter Lubna V. , Franks Ashley E. , Weis Robert M. , Sandler Steven J. 
Published: January 2017

ABSTRACT

Geobacter sulfurreducens
, an anaerobic metal-reducing bacterium, possesses type IV pili. These pili are intrinsic structural elements in biofilm formation and, together with a number of
c
-type cytochromes, are thought to serve as conductive nanowires enabling long-range electron transfer (ET) to metal oxides and graphite anodes. Here, we report that a posttranslational modification of a nonconserved amino acid residue within the PilA protein, the structural subunit of the type IV pili, is crucial for growth on insoluble extracellular electron acceptors. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the secreted PilA protein revealed a posttranslational modification of tyrosine-32 with a moiety of a mass consistent with a glycerophosphate group. Mutating this tyrosine into a phenylalanine inhibited cell growth with Fe(III) oxides as the sole electron acceptor. In addition, this amino acid substitution severely diminished biofilm formation on graphite surfaces and impaired current output in microbial fuel cells. These results demonstrate that the capability to attach to insoluble electron acceptors plays a crucial role for the cells' ability to utilize them. The work suggests that glycerophosphate modification of Y32 is a key factor contributing to the surface charge of type IV pili, influencing the adhesion of
Geobacter
to specific surfaces.

IMPORTANCE
Type IV pili are bacterial appendages that function in cell adhesion, virulence, twitching motility, and long-range electron transfer (ET) from bacterial cells to insoluble extracellular electron acceptors. The mechanism and role of type IV pili for ET in
Geobacter sulfurreducens
is still a subject of research. In this study, we identified a posttranslational modification of the major
G. sulfurreducens
type IV pilin, suggested to be a glycerophosphate moiety. We show that a mutant in which the glycerophosphate-modified tyrosine-32 is replaced with a phenylalanine has reduced abilities for ET and biofilm formation compared with those of the wild type. The results show the importance of the glycerophosphate-modified tyrosine for surface attachment and electron transfer in electrode- or Fe(III)-respiring
G. sulfurreducens
cells.
The N Terminus of the PduB Protein Binds the Protein Shell of the Pdu Microcompartment to Its Enzymatic Core
Authors: Lehman Brent P. , Chowdhury Chiranjit , Bobik Thomas A. 
Published: January 2017

ABSTRACT
Bacterial microcompartments (MCPs) are extremely large proteinaceous organelles that consist of an enzymatic core encapsulated within a complex protein shell. A key question in MCP biology is the nature of the interactions that guide the assembly of thousands of protein subunits into a well-ordered metabolic compartment. In this report, we show that the N-terminal 37 amino acids of the PduB protein have a critical role in binding the shell of the 1,2-propanediol utilization (Pdu) microcompartment to its enzymatic core. Several mutations were constructed that deleted short regions of the N terminus of PduB. Growth tests indicated that three of these deletions were impaired MCP assembly. Attempts to purify MCPs from these mutants, followed by gel electrophoresis and enzyme assays, indicated that the protein complexes isolated consisted of MCP shells depleted of core enzymes. Electron microscopy substantiated these findings by identifying apparently empty MCP shells but not intact MCPs. Analyses of 13 site-directed mutants indicated that the key region of the N terminus of PduB required for MCP assembly is a putative helix spanning residues 6 to 18. Considering the findings presented here together with prior work, we propose a new model for MCP assembly.

IMPORTANCE
Bacterial microcompartments consist of metabolic enzymes encapsulated within a protein shell and are widely used to optimize metabolic process. Here, we show that the N-terminal 37 amino acids of the PduB shell protein are essential for assembly of the 1,2-propanediol utilization microcompartment. The results indicate that it plays a key role in binding the outer shell to the enzymatic core. We propose that this interaction might be used to define the relative orientation of the shell with respect to the core. This finding is of fundamental importance to our understanding of microcompartment assembly and may have application to engineering microcompartments as nanobioreactors for chemical production.
Validation of a care pathway for the use of faecal calprotectin in monitoring patients with Crohn's disease
Authors: Turvill James , Rook Lisa , Rawle Maxine , Robins Gerry , Smale Simon , Kant Prashant , Phillips Anne 
Published: January 2017

IntroductionWe have previously published an evidence-based care pathway for the use of faecal calprotectin (FC) to monitor patients with Crohn's disease established on therapy. Patients are treated as low, intermediate or high risk of continuing Crohn's disease activity based on their FC, whatever their phenotype and surgical status are. Low-risk patients (FC <100 µg/g) are offered 12 monthly follow-ups or step down of therapy if asymptomatic or initial expectant symptomatic treatment. Intermediate-risk patients (FC 100–250 µg/g) are reviewed at 6 months with a repeat FC. High-risk patients (two consecutive FCs >250 µg/g) are flagged up to the responsible clinician as likely having an active Crohn's disease.MethodsTo validate this care pathway over a 2-year period, by determining its negative predictive value (NPV) and positive predictive value (PPV).Results123 patients were managed by means of the care pathway for a mean of 24.4 months. The NPV and PPV were 0.97 (CI 0.93 to 0.98) and 0.85 (CI 0.80 to 0.94), respectively (sensitivity: 0.92 (0.83 to 0.96) and specificity: 0.95 (0.92 to 0.98)). Importantly 69% of patients with FC >250 µg/g were in clinical remission, the care pathway identifying patients who would benefit from presymptomatic disease modification.ConclusionsThis validation of a pragmatic clinical care pathway demonstrates a safe and effective mechanism by which to use FC to monitor risk of disease activity in patients with Crohn's disease established on therapy. It provides a framework for prioritising follow-up and for identifying patients at risk of continuing disease activity or those in whom therapy could be stepped down.
Novel exon–exon breakpoint inCIC-DUX4fusion sarcoma identified by anchored multiplex PCR (Archer FusionPlex Sarcoma Panel)
Authors: Loke Benjamin Nathanael , Lee Victor Kwan Min , Sudhanshi Jain , Wong Meng Kang , Kuick Chik Hong , Puhaindran Mark , Chang Kenneth Tou En 
Published: January 2017

AimsWe describe the clinical and pathological features and novel genetic findings of a case ofCIC-DUX4sarcoma occurring in the thigh of a 35-year-old man.MethodsFusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was used to identify the novel fusion breakpoints of thisCIC-DUX4sarcoma using formalin-fixed and paraffin-embedded tumour material.ResultsThisCIC-DUX4sarcoma has a novel fusion breakpoint between exon 20 of theCICgene and exon 1 of theDUX4gene.ConclusionsThis case report describes an additional case ofCIC-DUX4sarcoma with a novel fusion breakpoint, and demonstrates the value of this next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) in both diagnosis for patient care and in identification of a novel fusion breakpoint in this tumour type.
Combining Chk1/2 Inhibition with Cetuximab and Radiation Enhances In Vitro and In Vivo Cytotoxicity in Head and Neck Squamous Cell Carcinoma
Authors: Zeng Ling , Beggs Reena R. , Cooper Tiffiny S. , Weaver Alice N. , Yang Eddy S. 
Published: January 2017

Abstract
EGFR inhibition and radiotherapy are potent inducers of DNA damage. Checkpoint kinases 1 and 2 (Chk1/2) are critical regulators of the DNA-damage response, controlling cell-cycle checkpoints that may permit recovery from therapy-associated genomic stress. We hypothesized that Chk1/2 inhibition (CHKi) with prexasertib may enhance cytotoxicity from EGFR inhibition plus radiotherapy in head and neck squamous cell carcinoma (HNSCC). In this study, we found that the addition of CHKi to the EGFR inhibitor cetuximab with and without radiotherapy significantly decreased cell proliferation and survival fraction in human papillomavirus virus (HPV)-positive and HPV-negative HNSCC cell lines. Reduced proliferation was accompanied by decreased checkpoint activation, induced S-phase accumulation, persistent DNA damage, and increased caspase cleavage and apoptosis. Importantly, a significant tumor growth delay was observed in vivo in both HPV-positive and HPV-negative cell line xenografts receiving triple combination therapy with CHKi, cetuximab, and radiotherapy without a concomitant increase in toxicity as assessed by mouse body weight. Taken together, the combination of CHKi with cetuximab plus irradiation displayed significant antitumor effects in HNSCCs both in vitro and in vivo, suggesting that this combination therapy may increase clinical benefit. A clinical trial to test this treatment for patients with head and neck cancer is currently ongoing (NCT02555644). Mol Cancer Ther; 16(4); 591–600. ©2017 AACR.
The interaction between equipoise and logistics in clinical trials: A case study
Authors: Warshaw Meredith G , Carey Vincent J , McFarland Elizabeth J , Dawson Liza , Abrams Elaine , Melvin Ann , Fairlie Lee , Spiegel Hans , Jay Jonathan , Agwu Allison L ,   for the IMPAACT P1094 Team
Published: January 2017

Introduction: Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Background: Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician’s sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers’ willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. Case Study: A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. Discussion: When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.
Acute graft-versus-host disease is regulated by an IL-17–sensitive microbiome
Authors: Varelias Antiopi , Ormerod Kate L. , Bunting Mark D. , Koyama Motoko , Gartlan Kate H. , Kuns Rachel D. , Lachner Nancy , Locke Kelly R. , Lim Chun Y. , Henden Andrea S. , Zhang Ping , Clouston Andrew D. , Hasnain Sumaira Z. , McGuckin Michael A. , Blazar Bruce R. , MacDonald Kelli P. A. , Hugenholtz Philip , Hill Geoffrey R. 
Published: January 2017

Key PointsRecipient-derived IL-17A is critical for the prevention of intestinal acute GVHD. Increased susceptibility to acute GVHD can be transferred to WT mice via cohousing with IL-17RA or IL-17RC–deficient mice.
The Hunchback temporal transcription factor establishes, but is not required to maintain, early-born neuronal identity
Authors: Hirono Keiko , Kohwi Minoree , Clark Matt Q. , Heckscher Ellie S. , Doe Chris Q. 
Published: January 2017

Abstract

Background

Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window. Surprisingly, nothing is currently known about whether Hb acts in neuroblasts or post-mitotic neurons (or both) to specify first-born neuronal identity.

Methods
Here we selectively remove Hb from post-mitotic neurons, and assay the well-characterized NB7-1 and NB1-1 lineages for defects in neuronal identity and function.

Results
We find that loss of Hb from embryonic and larval post-mitotic neurons does not affect neuronal identity. Furthermore, removing Hb from post-mitotic neurons throughout the entire CNS has no effect on larval locomotor velocity, a sensitive assay for motor neuron and pre-motor neuron function.

Conclusions
We conclude that Hb functions in progenitors (neuroblasts/GMCs) to establish heritable neuronal identity that is maintained by a Hb-independent mechanism.
We suggest that Hb acts in neuroblasts to establish an epigenetic state that is permanently maintained in early-born neurons.
Detailed archaeomagnetic study of a ceramic workshop at Kato Achaia: New directional data and archaeomagnetic dating in Greece.
Authors: Tema E. 
Published: January 2017

New archaeomagnetic results from two ancient kilns excavated at Kato Achaia, southern Greece, are presented. According to archaeological evidence, both kilns were part of a bigger ceramic workshop, probably used for the production of bricks or ceramics. Systematic archaeomagnetic sampling was carried out collecting 9 brick samples from the first kiln (KL3) and 12 brick samples from the second kiln (KL5). Magnetic mineralogy measurements have been carried out in order to determine the main magnetic carrier of the samples and to check their thermal stability. Standard thermal demagnetization procedures have been used to determine the archaeomagnetic direction registered by the bricks during their last firing. The direction of the Characteristic Remanent Magnetization (ChRM) has been obtained from principal component analysis and the kilns mean directions were calculated using Fisher statistics. The archaeomagnetic ages of both kilns were determined using the most recent developments in data elaboration and were calculated after comparison of the kilns declination and inclination with the reference curves produced by the SCHA.DIF.3K European regional geomagnetic field model. Dating results are in good agreement with archaeological evidence of the site and suggest that both kilns were in use during Hellenistic times.
Stochastic analysis of earthquake activity in two seismogenic fault systems in Greece.
Authors: Gkarlaouni Ch. , Papadimitriou E. , Lasocki S. , Lizurek G. , Karakostas V. , Kilias A. 
Published: January 2017

Possible systematic variations in earthquake occurrence and fluctuations in seismicity behaviourof two seismically active regions in Greece which share common seismotectonic properties, is the aim of this study. Mygdonia graben in northern Greeceis characterized by arather moderate background seismicity, with small earthquakes between 2008-2012 whereas Corinth Gulf in southern Greeceexhibits a constantly high seismicity rate with several seismic activations during the recent instrumental period or before. The statistical approach of seismicity was accomplished, regardingthe magnitude, the inter-event time and distance for recent seismicity as a tool to quantify complex earthquake occurrence ordense spatial andtemporal clustering. For this reason, complete catalogues were compiled for the time period of the study. Probabilistic tests such as the smoothed bootstrap test for modality and bump–hunt were employed in order to unveil the complexity of the probability density function distribution of the above parameters. On the other handspatial earthquake distribution wasalso investigated under the frameof their fractal properties since the fractal coefficientcan largely express the clustering degree of seismicity. The goal of this stochasticanalysisis the quantification of the differentiationin seismicity propertiesinthese two important seismogenic normal fault populations in the back arc Aegean area.
"Geo-characterization" of selected areas in Crete, Greece, towards realistic assessment of seismic design actions
Authors: Vafidis A. , Steiakakis M. , Agioutantis Z. , Andronikidis N. , Kritikakis G. , Economou N. , Pandi K. , Spanoudakis N. , Savvaidis A. , Margaris B. , Theodoulidis N. , Lekidis V. , Karakostas Ch. , Mangriotis M. D. , Kalogeras I. , Koutrakis S. , Rozos D. , Loupasakis C. , Rondoyanni Th. , Tsangaratos P. , Dikmen U. , Papadopoulos N. , Sarris A. , Soupios P. , Kokkinou E. , Papadopoulos I. , Kouli M. , Vallianatos F. 
Published: January 2017

The geo-characterization of site conditions is crucial for the estimation of regional elastic spectra. The work to be done in the framework of the “GEO-CHARACTERIZATION” THALIS-project, will combine geotechnical and geophysical methods and evaluate them to estimate critical geotechnical parameters. Although geotechnical tests in lab may provide more accurate estimates of geotechnical parameters, they require costly and time consuming drilling procedures. On the other hand geophysical methods are useful in providing estimates in situ of subsurface physical properties, which are not directly related to geotechnical parameters. Within “GEO-CHARACTERIZATION” THALIS-project a pilot survey for geotechnical characterization at selected sites of Hellenic Accelerometric Network in Crete will be conducted by employing geotechnical, geological and geophysical techniques. Subsequently, by correlating “geo-data” collected within this project, relations of certain mechanical parameters obtained in laboratory or/and in situ with geophysical parameters for typical geologic formations and soils will be established. The “GEO-CHARACTERIZATION” project, will focus on the influence of dynamic loads on geotechnical phenomena related to the static stress field variation, the estimation of site effects due to seismic motion and the proposal of regional elastic spectra for seismic provisions as well as their comparison with the corresponding elastic design spectra of Eurocode 8 (EC8).
H Ποίηση μέσα στη Στιγμή ή η Στιγμή μέσα στην Ποίηση
Authors: Ioannou Yiannis E. 
Published: January 2017

Το θέμα της ποιητικής στιγμής δεν είναι νέο στη γαλλική ποίηση. Πολλοί είναι οι ποιητές που προσέγγισαν το θέμα του χρόνου και επικεντρώθηκαν στη δυνατότητα αποδιάρθρωσης του, και στη βίωση μέσα από τη διάρκεια τους, των συστατικών του στιγμών. Στη νεότερη και σύγχρονη γαλλική ποίηση, προχωρά)ντας ένα βήμα παραπέρα, ποιητές όπως ο Baudelaire, ο Rimbaud, ο Char και θεωρητικοί όπως ο Bachelard και ο Poulet αποδίδουν ή μελετούν τη διάρκεια και τη σημασία της ποιητικής στιγμής και γενικότερα του χρόνου μέσα στη διαδικασία της καλλιτεχνικής δημιουργίας. Μερικοί απ' αυτούς, έμμεσα ή άμεσα, συνειδητά ή ασυνείδητα συσχετίζουν τη διάρκεια μέσα στο στιγμιαίο και το φευγαλέο με το φαινόμενο της έμπνευσης. Ο Ελύτης, με τη σειρά του, ενήμερος και επηρεασμένος από g; τη γενεαλογία αυτή, διατυπώνει ενδιαφέρουσες απόψεις γύρω από το θέμα. Είναι η *~Γ έμπνευση μια στιγμιαία αναλαμπή που εκδηλώνεται και εξαφανίζεται αμέσο, ή μήπως πρόκειται απλά για μια κατάσταση αυτοπειθαρχίας που [κπορεί να δημιουργηθεί ανά πάσα στιγμή; Μπορεί, όπως στην περίπτωση των υπερρεαλιστών, να εκβιασθεί ή όχι; Ή ακόμα, ένα καλό ποίημα είναι συνολικά εμπνευσμένο ή μόνο μερικοί στίχοι ή εικόνες μπορούν να ανταποκριθούν στον χαρακτηρισμό αυτό, ενώ το υπόλοιπο είναι αποτέλεσμα της εντατικής και επίπονης επεξεργασίας του κειμένου; Η μελέτη της ποίησης μέσα στη στιγμή ή αντίστροφα, της στιγμής μέσα στην ποίηση, μπορεί νομίζουμε να φωτίσει το θέμα από μιά νέα οπτική γωνία και να θέσει ξανά το πρόβλημα της καλλιτεχνικής δημιουργίας γενικότερα.