bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linearizing Structures
Authors: Bachrach Asaf , Katzir Roni 
Published: January 2017

AbstractThe linearization of unboundedly many syntactic structures given a finite number of ordering instructions poses a compositionality problem similar to the semantic problem of determining the meanings of unboundedly many structures. We discuss this challenge and use various constructions such as Right‐Node Raising that have been argued to involve multidominance—and that combine a remarkable productivity across and inside languages with a sensitivity to linear order—to tease apart different theories of linearization. We use data from such constructions, including new data provided in the paper, to argue in favor of a specific view of linearization first proposed in Bachrach & Katzir, one in which linearization compatibility requirements are computed very locally, at every node in the structure.
A review of maternal alloimmunisation to Rh D in Northern Ireland
Authors: McCauley C. J. , Morris K. , Maguire K. 
Published: January 2017

SUMMARYObjectivesTo estimate the current incidence of maternal sensitisation to Rhesus (Rh) D in Northern Ireland, examine adherence to recommendations for administration of anti‐D immunoglobulin and identify potential causes for all cases of anti‐D alloimmunisation sensitisation from January 2010 to September 2015.BackgroundPost‐partum anti‐D immunoglobulin administered to Rh D‐negative women and routine antenatal anti‐D prophylaxis have greatly reduced the incidence of haemolytic disease of the fetus and newborn due to immune anti‐D. Despite these measures, anti‐D alloimmunisation sensitisation continues to occur, albeit much less frequently than in the past.Methods/MaterialsThis was a retrospective review of new sensitisations to Rh D detected in antenatal records between January 2010 and September 2015 in Northern Ireland. A review of patient notes and laboratory data was carried out to examine adherence to standards and identify potential causes of sensitisation.ResultsA total of 67 new sensitisations to Rh D were identified over a 69‐month period, and the sensitisation rate for the full calendar years 2010–2014 was 0·310%. Only 4% of cases appear to have been preventable, with two cases involving failure to adhere to guidelines.ConclusionA total 96% of sensitisations occurred despite full compliance with guidelines. In a large proportion, sensitisation occurred following delivery (51%). A change in practice in Northern Ireland is under consideration to increase the dose of anti‐D immunoglobulin given following delivery from 500 to 1500 U in an attempt to reduce these sensitisations.
Task‐sharing with nurses to enhance access to HIV treatment in Côte d'Ivoire
Authors: McNairy Margaret L. , Bashi Jules B. , Chung Hannah , Wemin Louise , Lorng Marie‐Nicole Akpro , Brou Hermann , Nioble Cyprien , Lokossue A. , Abo Kouame , Achi Delphine , Ouattara Kiyali , Sess Daniel , Sanogo Pongathie Adama , Ekra Alexandre , Ettiegne‐Traore Virginie , Diabate Conombo J. , Abrams Elaine J. , El‐Sadr Wafaa M. 
Published: January 2017

AbstractObjectiveWe report the first national programme in Côte d'Ivoire to evaluate the feasibility of nurse‐led HIV care as a model of task‐sharing with nurses to increase coverage and decentralisation of HIV services.MethodsTwenty‐six public HIV facilities implemented either a nurse‐with‐onsite‐physician or a nurse‐with‐visiting‐physician model of HIV task‐sharing. Routinely collected patient data were reviewed to analyse patient characteristics of those enrolling in care and initiating antiretroviral therapy (ART). Retention, loss to programme and death were compared across facility‐level characteristics.ResultsA total of 1224 patients enrolled in HIV care, with 666 initiating ART, from January 2012 to May 2013 (median follow‐up 13 months). The majority (94%) were adults ≥15 years. Fourteen facilities provided ART initiation for the first time during the pilot period; 20 facilities were primary level. Nurse‐led care with a visiting physician was provided in 14 of the primary‐level facilities. Nurse‐led ART care with an onsite physician was provided in all secondary‐level facilities and six of the primary‐level facilities. During the pilot, 567 (85%) of patients were retained, 28 (4.2%) died, 47 (7.1%) were lost to follow‐up, and 24 (3.6%) transferred. Five deaths (10.9%) were recorded among children as compared to 23 deaths (3.7%) among adults (P = 0.037). There were no differences in retention by model of nurse‐led ART care.ConclusionTask‐sharing of HIV care and ART initiation with nurses in Côte d'Ivoire is feasible. This pilot illustrates two models of nurse‐led HIV care and has informed national policy on nurse‐led HIV care in Côte d'Ivoire.
Draft Genome Sequences of Three Aeromonas hydrophila Isolates from Catfish and Tilapia
Authors: Tekedar Hasan C. , Kumru Salih , Kalindamar Safak , Karsi Attila , Waldbieser Geoffrey C. , Sonstegard Tad , Schroeder Steven G. , Liles Mark R. , Griffin Matt J. , Lawrence Mark L. 
Published: January 2017

ABSTRACT

Aeromonas hydrophila
is a Gram-negative bacterium that is particularly adapted to freshwater environments and can cause severe infections in fish and humans. Here, we report the draft genomes of three
A. hydrophila
catfish and tilapia isolates.
Rapid Aminoglycoside NP Test for Rapid Detection of Multiple Aminoglycoside Resistance in Enterobacteriaceae
Authors: Nordmann Patrice , Jayol Aurélie , Dobias Jan , Poirel Laurent 
Published: January 2017

ABSTRACT

The rapid aminoglycoside NP (Nordmann/Poirel) test was developed to rapidly identify multiple aminoglycoside (AG) resistance in
Enterobacteriaceae
. It is based on the detection of the glucose metabolism related to enterobacterial growth in the presence of a defined concentration of amikacin plus gentamicin. Formation of acid metabolites was evidenced by a color change (orange to yellow) of the red phenol pH indicator. The rapid aminoglycoside NP test was evaluated by using bacterial colonies of 18 AG-resistant isolates producing 16S rRNA methylases, 20 AG-resistant isolates expressing AG-modifying enzymes (acetyl-, adenyl-, and phosphotransferases), and 10 isolates susceptible to AG. Its sensitivity and specificity were 100% and 97%, respectively, compared to the broth dilution method, which was taken as the gold standard for determining aminoglycoside resistance. The test is inexpensive, rapid (<2 h), and implementable worldwide.
Molecular and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Characterization of Clinically Significant Melanized Fungi in India
Authors: Singh Ashutosh , Singh Pradeep Kumar , Kumar Anil , Chander Jagdish , Khanna Geetika , Roy Pradip , Meis Jacques F. , Chowdhary Anuradha 
Published: January 2017

ABSTRACT

Melanized or black fungi are a heterogeneous group of fungi causing cutaneous to systemic diseases with high mortality. These fungi are rarely reported as agents of human infections, primarily due to difficulties in their classical identification. In this study, we examined, using molecular methods and matrix-assisted laser desorption ioniazation–time of flight mass spectrometry (MALDI-TOF MS), the diversity of melanized fungi (MF) isolated from patients in 19 medical centers in India. Overall, during a 4-year period, 718 (5.3%) clinical specimens yielded MF. Of these, 72 (10%) isolates had clinical significance and were identified primarily by sequencing the internal transcribed spacer and large subunit (LSU) regions. MF represented 21 genera comprising 29 species, the majority of them belonging to the orders Pleosporales (50%) and Chaetothyriales (22%). Among the 29 fungal species identified in this study, only 6 (20%) species were identified by the MALDI-TOF MS due to the limited commercial database of Bruker Daltonics for MF. However, a 100% identification rate of 20 additional species identified in this study was obtained by constructing an in-house database using 24- to 96-h-old liquid cultures. Further, the CLSI broth microdilution method revealed low MICs for posaconazole (≤1 μg/ml) and voriconazole (≤2 μg/ml) in 96% and 95% of isolates, respectively. Skin/subcutaneous and sino-nasal and pulmonary phaeohyphomycosis due to MF were diagnosed in 21.4% (
n
= 15) and 28.5% (
n
= 20) of cases. Also, 10% of patients had central nervous system involvement (
n
= 7), and 3 cases of fungal osteomyelitis due to
Cladophialophora bantiana
and
Corynespora
spp. were observed.
Herpes Simplex Virus 1 UL24 Abrogates the DNA Sensing Signal Pathway by Inhibiting NF-κB Activation
Authors: Xu Haiyan , Su Chenhe , Pearson Angela , Mody Christopher H. , Zheng Chunfu 
Published: January 2017

ABSTRACT
Cyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of antiviral genes such as type I interferons (IFNs), and the production of inflammatory cytokines. HSV-1 UL24 is widely conserved among members of the herpesviruses family and is essential for efficient viral replication. In this study, we found that ectopically expressed UL24 could inhibit cGAS-STING-mediated promoter activation of IFN-β and interleukin-6 (IL-6), and UL24 also inhibited interferon-stimulatory DNA-mediated IFN-β and IL-6 production during HSV-1 infection. Furthermore, UL24 selectively blocked nuclear factor κB (NF-κB) but not IFN-regulatory factor 3 promoter activation. Coimmunoprecipitation analysis demonstrated that UL24 bound to the endogenous NF-κB subunits p65 and p50 in HSV-1-infected cells, and UL24 was also found to bind the Rel homology domains (RHDs) of these subunits. Furthermore, UL24 reduced the tumor necrosis factor alpha (TNF-α)-mediated nuclear translocation of p65 and p50. Finally, mutational analysis revealed that the region spanning amino acids (aa) 74 to 134 of UL24 [UL24(74–134)] is responsible for inhibiting cGAS-STING-mediated NF-κB promoter activity. For the first time, UL24 was shown to play an important role in immune evasion during HSV-1 infection.

IMPORTANCE
NF-κB is a critical component of the innate immune response and is strongly induced downstream of most pattern recognition receptors (PRRs), leading to the production of IFN-β as well as a number of inflammatory chemokines and interleukins. To establish persistent infection, viruses have evolved various mechanisms to counteract the host NF-κB pathway. In the present study, for the first time, HSV-1 UL24 was demonstrated to inhibit the activation of NF-κB in the DNA sensing signal pathway via binding to the RHDs of the NF-κB subunits p65 and p50 and abolishing their nuclear translocation.
Rhinovirus C, Asthma, and Cell Surface Expression of Virus Receptor CDHR3
Authors: Palmenberg Ann C. 
Published: January 2017

ABSTRACT
Human rhinoviruses (RVs) of the A, B, and C species are defined agents of the common cold. But more than that, RV-A and RV-C are the dominant causes of hospitalization category infections in young children, especially those with asthma. The use of cadherin-related family member 3 (CDHR3) by RV-C as its cellular receptor creates a direct phenotypic link between human genetics (G versus A alleles cause Cys529 versus Tyr529 protein variants) and the efficiency with which RV-C can infect cells. With a lower cell surface display density, the human-specific Cys529 variant apparently confers partial protection from the severest virus-induced asthma episodes. Selective pressure favoring the Cys529 codon may have coemerged with the evolution of RV-C and helped shape modern human genomes against the virus-susceptible, albeit ancestral Tyr529.
Glycosylation of the Hemagglutinin Protein of H5N1 Influenza Virus Increases Its Virulence in Mice by Exacerbating the Host Immune Response
Authors: Zhao Dongming , Liang Libin , Wang Shuai , Nakao Tomomi , Li Yanbing , Liu Liling , Guan Yuntao , Fukuyama Satoshi , Bu Zhigao , Kawaoka Yoshihiro , Chen Hualan 
Published: January 2017

ABSTRACT
The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in nature and threaten public health. Although several viral determinants and host factors that influence the virulence of HPAI H5N1 viruses in mammals have been identified, the detailed molecular mechanism remains poorly defined and requires further clarification. In our previous studies, we characterized two naturally isolated HPAI H5N1 viruses that had similar viral genomes but differed substantially in their lethality in mice. In this study, we explored the molecular determinants and potential mechanism for this difference in virulence. By using reverse genetics, we found that a single amino acid at position 158 of the hemagglutinin (HA) protein substantially affected the systemic replication and pathogenicity of these H5N1 influenza viruses in mice. We further found that the G158N mutation introduced an N-linked glycosylation at positions 158 to 160 of the HA protein and that this N-linked glycosylation enhanced viral productivity in infected mammalian cells and induced stronger host immune and inflammatory responses to viral infection. These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.

IMPORTANCE
Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to evolve in nature and threaten human health. Key mutations in the virus hemagglutinin (HA) protein or reassortment with other pandemic viruses endow HPAI H5N1 viruses with the potential for aerosol transmissibility in mammals. A thorough understanding of the pathogenic mechanisms of these viruses will help us to develop more effective control strategies; however, such mechanisms and virulent determinants for H5N1 influenza viruses have not been fully elucidated. In this study, we identified glycosylation at positions 158 to 160 of the HA protein of two naturally occurring H5N1 viruses as an important virulence determinant. This glycosylation event enhanced viral productivity, exacerbated the host response, and thereby contributed to the high pathogenicity of H5N1 virus in mice.
The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis
Authors: Gonçalves-Carneiro Daniel , McKeating Jane A. , Bailey Dalan 
Published: January 2017

ABSTRACT
The signaling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to colocalize with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells. MeV infection was dependent on these dynamic cytoskeletal changes as well as fluid uptake through a macropinocytosis-like pathway as chemical inhibition of these processes inhibited entry. Moreover, we identified a role for the RhoA-ROCK-myosin II signaling axis in this MeV internalization process, highlighting a novel role for this recently characterized pathway in virus entry. Our study shows that MeV can hijack a microbial sensor normally involved in bacterial phagocytosis to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis, and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 min of viral attachment. Measles virus remains a significant cause of mortality in human populations, and this research sheds new light on the very first steps of infection of this important pathogen.

IMPORTANCE
Measles is a significant disease in humans and is estimated to have killed over 200 million people since records began. According to current World Health Organization statistics, it still kills over 100,000 people a year, mostly children in the developing world. The causative agent, measles virus, is a small enveloped RNA virus that infects a broad range of cells during infection. In particular, immune cells are infected via interactions between glycoproteins found on the surface of the virus and SLAMF1, the immune cell receptor. In this study, we have investigated the steps governing entry of measles virus into SLAMF1-positive cells and identified endocytic uptake of viral particles. This research will impact our understanding of morbillivirus-related immunosuppression as well as the application of measles virus as an oncolytic therapeutic.
Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination
Authors: Li Yingying , Zhou Ming , Luo Zhaochen , Zhang Yachun , Cui Min , Chen Huanchun , Fu Zhen F. , Zhao Ling 
Published: January 2017

ABSTRACTRabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization.IMPORTANCEExtending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological memory post-RABV vaccination. In this study, a novel rabies vaccine that expressed murine IL-7 was developed. This vaccine enhanced the numbers of Tfh cells and the GC responses, resulting in upregulated quantities of Bmem and PCs. Moreover, we found that the long-lived PCs that were elicited by the IL-7-expressing recombinant virus (rLBNSE-IL-7) were able to sustain VNA levels much longer than those elicited by the parent rLBNSE virus. Upon reexposure to the pathogen, the longevous Bmem, which maintained higher numbers for up to 360 dpi with rLBNSE-IL-7 compared to rLBNSE, could differentiate into antibody-secreting cells, resulting in rapid and potent secondary production of VNAs. These results suggest that the expression of IL-7 is beneficial for induction of potent and long-lasting humoral immune responses.
Functional Analysis of Hepatitis C Virus (HCV) Envelope Protein E1 Using a
trans
-Complementation System Reveals a Dual Role of a Putative Fusion Peptide of E1 in both HCV Entry and Morphogenesis
Authors: Tong Yimin , Chi Xiaojing , Yang Wei , Zhong Jin 
Published: January 2017

ABSTRACT

Hepatitis C virus (HCV) is an enveloped RNA virus belonging to the
Flaviviridae
family. It infects mainly human hepatocytes and causes chronic liver diseases, including cirrhosis and cancer. HCV encodes two envelope proteins, E1 and E2, that form a heterodimer and mediate virus entry. While E2 has been extensively studied, less has been done so for E1, and its role in the HCV life cycle still needs to be elucidated. Here we developed a new cell culture model for HCV infection based on the
trans
-complementation of E1. Virus production of the HCV genome lacking the E1-encoding sequence can be efficiently rescued by the ectopic expression of E1 in
trans
. The resulting virus, designated HCVΔE1, can propagate in packaging cells expressing E1 but results in only single-cycle infection in naive cells. By using the HCVΔE1 system, we explored the role of a putative fusion peptide (FP) of E1 in HCV infection. Interestingly, we found that the FP not only contributes to HCV entry, as previously reported, but also may be involved in virus morphogenesis. Finally, we identified amino acid residues in FP that are critical for biological functions of E1. In summary, our work not only provides a new cell culture model for studying HCV but also provides some insights into understanding the role of E1 in the HCV life cycle.

IMPORTANCE
Hepatitis C virus (HCV), an enveloped RNA virus, encodes two envelope proteins, E1 and E2, that form a heterodimeric complex to mediate virus entry. Compared to E2, the biological functions of E1 in the virus life cycle are not adequately investigated. Here we developed a new cell culture model for single-cycle HCV infection based on the
trans
-complementation of E1. The HCV genome lacking the E1-encoding sequence can be efficiently rescued for virus production by the ectopic expression of E1 in
trans
. This new model renders a unique system to dissect functional domains and motifs in E1. Using this system, we found that a putative fusion peptide in E1 is a multifunctional structural element contributing to both HCV entry and morphogenesis. Our work has provided a new cell culture model to study HCV and provides insights into understanding the biological roles of E1 in the HCV life cycle.
Inflammasomes in Myeloid Cells: Warriors Within
Authors: Jha Sushmita , Brickey W. June , Ting Jenny Pan-Yun 
Published: January 2017

ABSTRACT
The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor molecule; and procaspase-1, which is converted to caspase-1 upon inflammasome activation. Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice, and several have been genetically linked to human diseases. In most cases, the effector protein is a member of the NLR (nucleotide-binding domain leucine-rich repeat-containing) or NOD (nucleotide oligomerization domain)-like receptor protein family. However, other effectors have also been described, with the most notable being AIM-2 (absent in melanoma 2), which recognizes DNA to elicit inflammasome function. This review will focus on the role of the inflammasome in myeloid cells and its role in health and disease.