bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine
Authors: Longley Rhea J. , Halbroth Benedict R. , Salman Ahmed M. , Ewer Katie J. , Hodgson Susanne H. , Janse Chris J. , Khan Shahid M. , Hill Adrian V. S. , Spencer Alexandra J. 
Published: December 2016

ABSTRACT

Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the
Plasmodium falciparum
antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric
P. berghei
parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type
P. berghei
parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to
P. falciparum
parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate
P. falciparum
thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric
P. berghei
-
P. falciparum
parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type
P. berghei
; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced.
The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum
Authors: Reedy Jennifer L. , Negoro Paige E. , Feliu Marianela , Lord Allison K. , Khan Nida S. , Lukason Dan P. , Wiederhold Nathan P. , Tam Jenny M. , Mansour Michael K. , Patterson Thomas F. , Vyas Jatin M. 
Published: December 2016

ABSTRACT

Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on
Exserohilum rostratum
, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing
Exserohilum
. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production.
In vivo
soft tissue infection in wild-type mice demonstrated that
Exserohilum
provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to
Exserohilum
and that corticosteroids potently attenuate the immune response to this pathogen.
Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization
Authors: Hyre Amanda N. , Kavanagh Kylie , Kock Nancy D. , Donati George L. , Subashchandrabose Sargurunathan 
Published: December 2016

ABSTRACT

Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic
Escherichia coli
(UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens
Proteus mirabilis
and
Klebsiella pneumoniae
, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI.
Polynucleotide Phosphorylase, RNase E/G, and YbeY Are Involved in the Maturation of 4.5S RNA in Corynebacterium glutamicum
Authors: Maeda Tomoya , Tanaka Yuya , Wachi Masaaki , Inui Masayuki 
Published: December 2016

ABSTRACT

Corynebacterium glutamicum
has been applied for the industrial production of various metabolites, such as amino acids. To understand the biosynthesis of the membrane protein in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP is found in all three domains of life and plays an important role in the membrane insertion of proteins. SRP RNA is initially transcribed as precursor molecules; however, relatively little is known about its maturation. In
C. glutamicum
, SRP consists of the Ffh protein and 4.5S RNA lacking an Alu domain. In this study, we found that 3′-to-5′ exoribonuclease, polynucleotide phosphorylase (PNPase), and two endo-type RNases, RNase E/G and YbeY, are involved in the 3′ maturation of 4.5S RNA in
C. glutamicum
. The mature form of 4.5S RNA was inefficiently formed in Δ
rneG
Δ
pnp
mutant cells, suggesting the existence of an alternative pathway for the 3′ maturation of 4.5S RNA. Primer extension analysis also revealed that the 5′ mature end of 4.5S RNA corresponds to that of the transcriptional start site. Immunoprecipitated Ffh protein contained immature 4.5S RNA in Δ
pnp
, Δ
rneG
, and Δ
ybeY
mutants, suggesting that 4.5S RNA precursors can interact with Ffh. These results imply that the maturation of 4.5S RNA can be performed in the 4.5S RNA-Ffh complex.

IMPORTANCE
Overproduction of a membrane protein, such as a transporter, is useful for engineering of strains of
Corynebacterium glutamicum
, which is a workhorse of amino acid production. To understand membrane protein biogenesis in this bacterium, we investigated the process of signal recognition particle (SRP) assembly. SRP contains the Ffh protein and SRP RNA and plays an important role in the membrane insertion of proteins. Although SRP RNA is highly conserved among the three domains of life, relatively little is known about its maturation. We show that PNPase, RNase E/G, and YbeY are involved in the 3′ maturation of the SRP RNA (4.5S RNA) in this bacterium. This indicates that 3′ end processing in this organism is different from that in other bacteria, such as
Escherichia coli
.
Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages
Authors: Cairns M. D. , Preston M. D. , Hall C. L. , Gerding D. N. , Hawkey P. M. , Kato H. , Kim H. , Kuijper E. J. , Lawley T. D. , Pituch H. , Reid S. , Kullin B. , Riley T. V. , Solomon K. , Tsai P. J. , Weese J. S. , Stabler R. A. , Wren B. W. 
Published: December 2016

ABSTRACT

The diarrheal pathogen
Clostridium difficile
consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of
C. difficile
RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.
Testing for Cytomegalovirus in Pregnancy
Authors: Saldan Alda , Forner Gabriella , Mengoli Carlo , Gussetti Nadia , Palù Giorgio , Abate Davide 
Published: December 2016

ABSTRACT
Congenital cytomegalovirus (CMV) infection represents a relevant cause of deafness and neurological damage in newborns. Intrauterine CMV transmission might result after primary or nonprimary infections, though at different rates (30% versus 0.2%, respectively). At present, a prenatal diagnosis of CMV infection is based mainly on maternal serology, the detection of CMV-DNA in amniotic fluid and fetal blood, and ultrasound (US) and magnetic resonance imaging (MRI). Recent evidences suggest that congenital CMV infection may be an immune-mediated disease and that evaluation of humoral and especially T-cell immunities may improve the overall prenatal diagnosis. This review summarizes the most recent advancements in the diagnosis of maternal and prenatal CMV infections.
Integrating Advanced Molecular Technologies into Public Health
Authors: Gwinn Marta , MacCannell Duncan R. , Khabbaz Rima F. 
Published: December 2016

ABSTRACT
Advances in laboratory and information technologies are transforming public health microbiology. High-throughput genome sequencing and bioinformatics are enhancing our ability to investigate and control outbreaks, detect emerging infectious diseases, develop vaccines, and combat antimicrobial resistance, all with increased accuracy, timeliness, and efficiency. The Advanced Molecular Detection (AMD) initiative has allowed the Centers for Disease Control and Prevention (CDC) to provide leadership and coordination in integrating new technologies into routine practice throughout the U.S. public health laboratory system. Collaboration and partnerships are the key to navigating this transition and to leveraging the next generation of methods and tools most effectively for public health.
Autographa californica Multiple Nucleopolyhedrovirus AC83 is aPer OsInfectivity Factor (PIF) Protein Required for Occlusion-Derived Virus (ODV) and Budded Virus Nucleocapsid Assembly as well as Assembly of the PIF Complex in ODV Envelopes
Authors: Javed Muhammad Afzal , Biswas Siddhartha , Willis Leslie G. , Harris Stephanie , Pritchard Caitlin , van Oers Monique M. , Donly B. Cameron , Erlandson Martin A. , Hegedus Dwayne D. , Theilmann David A. 
Published: December 2016

ABSTRACTBaculovirus occlusion-derived virus (ODV) initiates infection of lepidopteran larval hosts by binding to the midgut epithelia, which is mediated byper osinfectivity factors (PIFs). Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes seven PIF proteins, of which PIF1 to PIF4 form a core complex in ODV envelopes to which PIF0 and PIF6 loosely associate. Deletion of anypifgene results in ODV being unable to bind or enter midgut cells. AC83 also associates with the PIF complex, and this study further analyzed its role in oral infectivity to determine if it is a PIF protein. It had been proposed that AC83 possesses a chitin binding domain that enables transit through the peritrophic matrix; however, no chitin binding activity has ever been demonstrated. AC83 has been reported to be found only in the ODV envelopes, but in contrast, the Orgyia pseudotsugata MNPV AC83 homolog is associated with both ODV nucleocapsids and envelopes. In addition, unlike knownpifgenes, deletion ofac83eliminates nucleocapsid formation. We propose a new model for AC83 function and show AC83 is associated with both ODV nucleocapsids and envelopes. We also further define the domain required for nucleocapsid assembly. The cysteine-rich region of AC83 is also shown not to be a chitin binding domain but a zinc finger domain required for the recruitment or assembly of the PIF complex to ODV envelopes. As such, AC83 has all the properties of a PIF protein and should be considered PIF8. In addition,pif7(ac110) is reported as the 38th baculovirus core gene.IMPORTANCEODV is essential for theper osinfectivity of the baculovirus AcMNPV. To initiate infection, ODV binds to microvilli of lepidopteran midgut cells, a process which requires a group of seven virion envelope proteins called PIFs. In this study, we reexamined the function of AC83, a protein that copurifies with the ODV PIFs, to determine its role in the oral infection process. A zinc finger domain was identified and a new model for AC83 function was proposed. In contrast to previous studies, AC83 was found to be physically located in both the envelope and nucleocapsid of ODV. By deletion analysis, the AC83 domain required for nucleocapsid assembly was more finely delineated. We show that AC83 is required for PIF complex formation and conclude that it is a trueper osinfectivity factor and should be called PIF8.
Unraveling the Armor of a Killer: Evasion of Host Defenses by African Swine Fever Virus
Authors: Reis Ana Luisa , Netherton Chris , Dixon Linda K. 
Published: December 2016

ABSTRACT

African swine fever is an acute hemorrhagic disease of pigs. Extensive recent spread in the Russian Federation and Eastern Europe has increased the risk to global pig production. The virus is a large DNA virus and is the only member of the
Asfarviridae
family. In pigs, the virus replicates predominantly in macrophages. We review how the virus overcomes the barriers to replication in the macrophage and the virus mechanism to inhibit key host defense pathways.
Randomised feasibility study of a novel experience-based internet intervention to support self-management in chronic asthma
Authors: Newhouse Nikki , Martin Angela , Jawad Sena , Yu Ly-Mee , Davoudianfar Mina , Locock Louise , Ziebland Sue , Powell John 
Published: December 2016

ObjectiveTo determine the feasibility of a randomised controlled trial (RCT) assessing the effects of an experience-based website as a resource for the self-management of chronic asthma.Design and settingFeasibility, single-blind RCT in 2 regions of England. Randomisation used computer-generated random number sequence in a 1:1 ratio, after baseline data collection, to website access for 2 weeks.ParticipantsAdults (age ≥18 years), with clinically diagnosed asthma as coded in their primary care electronic record, prescribed inhaled corticosteroids for at least 3 months in the previous year, were recruited from 9 general practices.InterventionThe EXPERT asthma intervention is an interactive PC/laptop/tablet/smartphone compatible website designed with extensive input from adults with asthma. It provides experience-based information and aims to support subjective perception of self-efficacy, self-management and improve health status.Outcome measuresPrimary outcomes were consent/recruitment, website usage and completion of outcome measures. Secondary outcomes included Partners in Health (PIH) questionnaire, the Chronic Disease Self-Efficacy Scale, the SF36 and the E-Health Impact Questionnaire. Participant blinding postrandomisation was not possible. The analysis was blind to allocation.ResultsRecruitment target exceeded. 148 participants randomised (73 intervention group). Age range 19–84 years; 59% female. 121 of 148 (84%; 62 intervention group) followed up. The median number of logins was 2 (IQR 2–3, range 1–48). Minimal differences of change from baseline between groups; both showed improvement in health state or management of their condition with no significant differences between arms. No adverse events.ConclusionsRecruitment and retention confirmed feasibility. The trends towards improved outcomes suggest that further research on digital interventions based on exposure to others’ personal experiences may be of value in the self-management of chronic asthma.Trial registration numberISRCTN29549695; Results.
Intra-arterial nitroglycerin as directed acute treatment in experimental ischemic stroke
Authors: Maniskas Michael E , Roberts Jill M , Trueman Rebecca , Learoyd Annastazia E , Gorman Amanda , Fraser Justin F , Bix Gregory J 
Published: December 2016

BackgroundNitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.ObjectiveTo examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.MethodsWe administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we performed a dose–response (3.12, 6.25, 12.5, and 25 µg/µL) analysis. Next, we looked at blood perfusion (flow) through the middle cerebral artery using laser Doppler flowmetry. Functional outcomes, including forced motor movement rotor rod, were assessed in the 3.12, 6.25, and 12.5 µg/µL groups. Histological analysis was performed using cresyl violet for infarct volume, and glial fibrillary activating protein (GFAP) and NeuN immunohistochemistry for astrocyte activation and mature neuron survival, respectively.ResultsOverall, we found that acute post-stroke IA GTN had little effect on vessel dilatation after 15 min. Functional analysis showed a significant difference between GTN (3.12 and 6.25 µg/µL) and control at post-stroke day 1. Histological measures showed a significant reduction in infarct volume and GFAP immunoreactivity and a significant increase in NeuN.ConclusionsThese results demonstrate that acute IA GTN is neuroprotective in experimental ischemic stroke and warrants further study as a potentially new stroke therapy.
Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K521 Polymorphism
Authors: Braig Friederike , Kriegs Malte , Voigtlaender Minna , Habel Beate , Grob Tobias , Biskup Karina , Blanchard Veronique , Sack Markus , Thalhammer Anja , Ben Batalla Isabel , Braren Ingke , Laban Simon , Danielczyk Antje , Goletz Steffen , Jakubowicz Elzbieta , Märkl Bruno , Trepel Martin , Knecht Rainald , Riecken Kristoffer , Fehse Boris , Loges Sonja , Bokemeyer Carsten , Binder Mascha 
Published: December 2016

Abstract
Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K521 (K-allele), which is expressed in &gt;40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation. In several EGFR-mediated cancer models, cetuximab failed to inhibit downstream signaling or to kill cells harboring a high K-allele frequency. Cetuximab affinity for EGFR-K521 was reduced slightly, but ligand-mediated EGFR activation was intact. We found a lack of glycan sialyation on EGFR-K521 that associated with reduced protein stability, suggesting a structural basis for reduced cetuximab efficacy. CetuGEX, an antibody with optimized Fc glycosylation targeting the same epitope as cetuximab, restored HNSCC sensitivity in a manner associated with antibody-dependent cellular cytotoxicity rather than EGFR pathway inhibition. Overall, our results highlight EGFR-K521 expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients. Further, they offer a preclinical rationale for the use of ADCC-optimized antibodies to treat tumors harboring this EGFR isoform. Cancer Res; 77(5); 1188–99. ©2016 AACR.
Orestes bojownikiem ruchu oporu, czyli mit Atrydów w filmie "Podróż komediantów" Theo Angelopoulosa
Authors: Łomanowska Iga 
Published: December 2016

Orestes as a resistance fighter, or the myth of the Atreides in Theo Angelopoulos’s film The travelling playersThe paper examines the use of the Atreides myth in Theo Angelopoulos’s film The travelling players (1975) in the context of the director’s interpretation of the phenomenon of myth. Angelopoulos treated myth as a set of archetypical situations and patterns of conduct constantly reproduced in the history of the world. He intertwined elements of classical stories with the history of Greece and the Byzantine tradition, thus showing their universal character. In The travelling players, Angelopoulos used the story of betrayed and murdered Agamemnon, who is avenged by his children: Orestes and Electra, but he moved it into modern times, setting the film in Greece of the 1940s and 1950s. The myth is reproduced with modulations: the most important events take place as a result of interventions of History, not fate or decisions of the gods. Moreover, the characters’ conflicts are enriched with a political dimension, as Angelopolous portrays the discord between their ideological stances. But the members of the acting company are as helpless in the face of events as the family of the king of Argos. Orestes bojownikiem ruchu oporu, czyli mit Atrydów w filmie Podróż komediantów Theo AngelopoulosaArtykuł jest analizą sposobu wykorzystania przez Theo Angelopoulosa mitu Atrydów w filmie Podróż komediantów (1975) w kontekście dokonanej przez niego interpretacji zjawiska mitu. Grecki reżyser traktował mit jako zbiór archetypicznych sytuacji i wzorów postępowania odtwarzanych nieustannie w dziejach świata. Elementy antycznych opowieści splatał w filmach z historią Grecji i tradycją bizantyjską, ujawniając ich uniwersalny charakter. W Podróży komediantów wykorzystał historię zdradzonego i zamordowanego Agamemnona, który zostaje pomszczony przez swoje dzieci: Orestesa i Elektrę, ale przeniósł ją w czasy współczesne, portretując Grecję lat 40. i 50. XX wieku. Mit zostaje zreprodukowany z modulacjami: kluczowe wydarzenia następują w wyniku interwencji historii, nie fatum czy decyzji bogów. Ponadto konflikty między postaciami zostają wzbogacone o wymiar polityczny, ponieważ Angelopoulos ukazuje rozdźwięk między ich postawami ideologicznymi. Jednak członkowie trupy aktorskiej pozostają wobec wydarzeń tak samo bezradni jak rodzina władcy Argolidy.