bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agreement at PF: An Argument from Partial Control
Authors: Landau Idan 
Published: January 2016

AbstractControlled null subjects (PRO) are semantically bound variables that bear morphological features. In certain environments of partial control, the morphological ϕ‐features (specifically, [person]) and the semantic value of PRO diverge. A natural explanation of the fact that the [person] feature of PRO is uninterpreted is that it is assigned at Phonological Form (PF). Given that this feature participates in agreement relations, we conclude that agreement must be (optionally or exclusively) a PF phenomenon.
Structural insights and membrane binding properties of MGD1, the major galactolipid synthase in plants
Authors: Rocha Joana , Sarkis Joe , Thomas Aline , Pitou Laurence , Radzimanowski Jens , Audry Magali , Chazalet Valérie , de Sanctis Daniele , Palcic Monica M. , Block Maryse A. , Girard‐Egrot Agnès , Maréchal Eric , Breton Christelle 
Published: January 2016

SummaryMonogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the major lipid components of photosynthetic membranes, and hence the most abundant lipids in the biosphere. They are essential for assembly and function of the photosynthetic apparatus. In Arabidopsis, the first step of galactolipid synthesis is catalyzed by MGDG synthase 1 (MGD1), which transfers a galactosyl residue from UDP‐galactose to diacylglycerol (DAG). MGD1 is a monotopic protein that is embedded in the inner envelope membrane of chloroplasts. Once produced, MGDG is transferred to the outer envelope membrane, where DGDG synthesis occurs, and to thylakoids. Here we present two crystal structures of MGD1: one unliganded and one complexed with UDP. MGD1 has a long and flexible region (approximately 50 amino acids) that is required for DAG binding. The structures reveal critical features of the MGD1 catalytic mechanism and its membrane binding mode, tested on biomimetic Langmuir monolayers, giving insights into chloroplast membrane biogenesis. The structural plasticity of MGD1, ensuring very rapid capture and utilization of DAG, and its interaction with anionic lipids, possibly driving the construction of lipoproteic clusters, are consistent with the role of this enzyme, not only in expansion of the inner envelope membrane, but also in supplying MGDG to the outer envelope and nascent thylakoid membranes.
A randomized, blinded, placebo‐controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors
Authors: Mast Alan E. , Bialkowski Walter , Bryant Barbara J. , Wright David J. , Birch Rebecca , Kiss Joseph E. , D'Andrea Pam , Cable Ritchard G. , Spencer Bryan R. 
Published: January 2016

BACKGROUNDThe historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored.STUDY DESIGN AND METHODSFrequent blood donors were randomly assigned into five arms for 2 years of follow‐up. Three double‐blinded arms provided 60 once‐daily pills after each donation (38, 19, or 0 mg of iron). Two single‐blinded arms provided iron status (ferritin) or no information letters after each donation. Ferritin, soluble transferrin receptor, and complete blood count were measured at each donation.RESULTSThere were 692 subjects enrolled and 393 completed the study. Subjects in pill groups deenrolled more than those in letter groups (39% vs. 7%). Adverse events occurred equally in subjects receiving iron or placebo pills. Of those completing the study, the prevalence of ferritin of less than 12 or less than 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19 or 38 mg of iron; iron status letter). Longitudinal analyses of all subjects showed improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups. The iron status letter group had little change in Hb.CONCLUSIONProviding 19 or 38 mg of daily iron or iron status information were effective and mostly equivalent interventions for mitigating iron deficiency in regular donors when compared at the end of the 2‐year longitudinal phase of the study. Donors without intervention had worsened iron deficiency with continued donation.
Maternal obesity associated with increase in natural killer T cells and CD8+ regulatory T cells in cord blood units
Authors: Gonzalez‐Espinosa Luis Octavio , Montiel‐Cervantes Laura Arcelia , Guerra‐Márquez Angel , Peñaflor‐Juárez Karina , Reyes‐Maldonado Elba , Vela‐Ojeda Jorge 
Published: January 2016

BACKGROUNDOne of the major limitations of umbilical cord blood (UCB) as hematopoietic stem cell source is its restricted cell number. In mothers who are candidates for stem cell donation, there are variables that affect the quantity and quality of UCB units. The aim of this study was to determine if obstetric, maternal, and fetal factors modify the number of lymphocyte subsets in UCB units.STUDY DESIGN AND METHODSThis was a prospective, observational study. In UCB units, the numbers of CD34, NK, NKT, iNKT, Type 1 dendritic cells (DCs), Type 2 DCs, T γδ, T CD4+, T CD8+ lymphocytes, CD4+CD25+FoxP3+, and CD8+CD25+FoxP3+ T regulatory (Treg) cells were quantified by flow cytometry.RESULTSFifty‐four UCB units were included; the donors’ mean weight was 75 kg (range, 52 to 102 kg) and they had a mean body mass index (BMI) of 30 kg/m2 (range 22 to 40 kg/m2), of which 12 (22%) had a normal BMI, 14 (26%) were overweight, and 28 (52%) were obese. The mean number of CD34+ cells was 4.45 × 106 (range, 0.7 × 106 to 20.5 × 106). The number of NKT, CD3+, CD4+, CD8+, and CD8+CD25+FoxP3+ Treg cells was significantly higher in overweight or obese mothers; CD34+ cells were decreased in the same group. The number of iNKT and CD34+ cells was decreased in newborns weighing above the average.CONCLUSIONSMaternal factors such as BMI, and fetal factors such as weight at birth, should be added to the selection criteria of UCB donors.
Electrochemical detection of Pseudomonas in wound exudate samples from patients with chronic wounds
Authors: Sismaet Hunter J. , Banerjee Anirban , McNish Sean , Choi Yongwook , Torralba Manolito , Lucas Sarah , Chan Agnes , Shanmugam Victoria K. , Goluch Edgar D. 
Published: January 2016

AbstractIn clinical practice, point‐of‐care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox‐active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE‐HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 μL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point‐of‐care diagnostic tool is planned.
The pathobiology of pig‐to‐primate xenotransplantation: a historical review
Authors: Cooper David K.C. , Ezzelarab Mohamed B. , Hara Hidetaka , Iwase Hayato , Lee Whayoung , Wijkstrom Martin , Bottino Rita 
Published: January 2016

AbstractThe immunologic barriers to successful xenotransplantation are related to the presence of natural anti‐pig antibodies in humans and non‐human primates that bind to antigens expressed on the transplanted pig organ (the most important of which is galactose‐α1,3‐galactose [Gal]), and activate the complement cascade, which results in rapid destruction of the graft, a process known as hyperacute rejection. High levels of elicited anti‐pig IgG may develop if the adaptive immune response is not prevented by adequate immunosuppressive therapy, resulting in activation and injury of the vascular endothelium. The transplantation of organs and cells from pigs that do not express the important Gal antigen (α1,3‐galactosyltransferase gene‐knockout [GTKO] pigs) and express one or more human complement‐regulatory proteins (hCRP, e.g., CD46, CD55), when combined with an effective costimulation blockade‐based immunosuppressive regimen, prevents early antibody‐mediated and cellular rejection. However, low levels of anti‐non‐Gal antibody and innate immune cells and/or platelets may initiate the development of a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. This pathogenic process is accentuated by the dysregulation of the coagulation‐anticoagulation systems between pigs and primates. The expression in GTKO/hCRP pigs of a human coagulation‐regulatory protein, for example, thrombomodulin, is increasingly being associated with prolonged pig graft survival in non‐human primates. Initial clinical trials of islet and corneal xenotransplantation are already underway, and trials of pig kidney or heart transplantation are anticipated within the next few years.
A multiple‐gene phylogeny reveals polyphyly among eastern North American Aphaenogaster species (Hymenoptera: Formicidae)
Authors: DeMarco Bernice B. , Cognato Anthony I. 
Published: January 2016

Twenty‐three Aphaenogaster species (Hymenoptera: Formicidae) occur in North America. While morphology and ecology define most species, the species limits of a group in the Eastern United States are unclear. In particular, the morphological and behavioural characters of A. carolinensis, A. picea and A. rudis overlap. These observations suggest that these three species are not monophyletic. We therefore tested the monophyly of Aphaenogaster in the context of molecular phylogenetic analyses. We used DNA data from five genes: CO1, CAD, EF1αF2, long‐wavelength rhodopsin and wingless, to reconstruct phylogenies for 44 Aphaenogaster and outgroup species. In the resulting trees, reconstructed using parsimony and Bayesian inference, species boundaries associated with well‐supported monophyletic clades of individuals in most of the 23 North American Aphaenogaster collected from multiple locations. However, some clades were unresolved, and both A. picea and A. rudis were not monophyletic. Although this may indicate that clades of multiple species represent fewer but morphologically varied species, given the short branch lengths, the lack of resolution may reflect the fact that these ants have recently radiated, and a lack of gene lineage sorting explains the non‐monophyly of species. Additional biological information concerning pre‐ and postmating barriers is needed before a complete revision of species boundaries for Aphaenogaster.
Ancient Babylonian astronomers calculated Jupiter’s position from the area under a time-velocity graph
Authors: Ossendrijver Mathieu 
Published: January 2016

Babylonian astronomers tracked Jupiter
Ancient Babylonian astronomers developed many important concepts that are still in use, including the division of the sky into 360 degrees. They could also predict the positions of the planets using arithmetic. Ossendrijver translated several Babylonian cuneiform tablets from 350 to 50 BCE and found that they contain a sophisticated calculation of the position of Jupiter. The method relies on determining the area of a trapezium under a graph. This technique was previously thought to have been invented at least 1400 years later in 14th-century Oxford. This surprising discovery changes our ideas about how Babylonian astronomers worked and may have influenced Western science.

Science
, this issue p.
482
Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel
Authors: Graf Erin H. , Simmon Keith E. , Tardif Keith D. , Hymas Weston , Flygare Steven , Eilbeck Karen , Yandell Mark , Schlaberg Robert 
Published: January 2016

ABSTRACT

Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (
n
= 42) and unselected (
n
= 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information.
The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype
Authors: Nishiyama Shoko , Lokugamage Nandadeva , Ikegami Tetsuro 
Published: January 2016

ABSTRACT

Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by “abortion storms” in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family
Bunyaviridae
, genus
Phlebovirus
) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments.

IMPORTANCE
Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP-12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38°C.
Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe
Authors: Bodewes Rogier , Zohari Siamak , Krog Jesper S. , Hall Matthew D. , Harder Timm C. , Bestebroer Theo M. , van de Bildt Marco W. G. , Spronken Monique I. , Larsen Lars E. , Siebert Ursula , Wohlsein Peter , Puff Christina , Seehusen Frauke , Baumgärtner Wolfgang , Härkönen Tero , Smits Saskia L. , Herfst Sander , Osterhaus Albert D. M. E. , Fouchier Ron A. M. , Koopmans Marion P. , Kuiken Thijs 
Published: January 2016

ABSTRACT

Influenza A viruses are major pathogens for humans, domestic animals, and wildlife, and these viruses occasionally cross the species barrier. In spring 2014, increased mortality of harbor seals (
Phoca vitulina
), associated with infection with an influenza A(H10N7) virus, was reported in Sweden and Denmark. Within a few months, this virus spread to seals of the coastal waters of Germany and the Netherlands, causing the death of thousands of animals. Genetic analysis of the hemagglutinin (HA) and neuraminidase (NA) genes of this seal influenza A(H10N7) virus revealed that it was most closely related to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different countries between April 2014 and January 2015 were obtained by Sanger sequencing and next-generation sequencing to describe the molecular epidemiology of the seal influenza A(H10N7) virus. The majority of sequence variation occurred in the HA gene, and some mutations corresponded to amino acid changes not found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host.

IMPORTANCE
Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species, cross-species transmission of influenza A viruses occurs occasionally. Wild waterfowl and shorebirds are the main reservoir for most influenza A virus subtypes, and spillover of influenza A viruses from birds to humans or other mammalian species may result in major outbreaks. In the present study, various sequencing methods were used to elucidate the genetic changes that occurred after the introduction and subsequent spread of an avian influenza A(H10N7) virus among harbor seals of northwestern Europe by use of various samples collected during the outbreak. Such detailed knowledge of genetic changes necessary for introduction and adaptation of avian influenza A viruses to mammalian hosts is important for a rapid risk assessment of such viruses soon after they cross the species barrier.
Functional Comparison of HBZ and the Related APH-2 Protein Provides Insight into Human T-Cell Leukemia Virus Type 1 Pathogenesis
Authors: Panfil Amanda R. , Dissinger Nathan J. , Howard Cory M. , Murphy Brandon M. , Landes Kristina , Fernandez Soledad A. , Green Patrick L. 
Published: January 2016

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that transform T cells
in vitro
but have distinct pathological outcomes
in vivo
. HTLV-1 encodes a protein from the antisense strand of its proviral genome, the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-1-mediated viral transcription and promotes cell proliferation, a high proviral load, and persistence
in vivo
. In adult T-cell leukemia/lymphoma (ATL) cell lines and patient T cells,
hbz
is often the only viral gene expressed. The antisense strand of the HTLV-2 proviral genome also encodes a protein termed APH-2. Like HBZ, APH-2 is able to inhibit Tax-2-mediated viral transcription and is detectable in most primary lymphocytes from HTLV-2-infected patients. However, unlike HBZ, the loss of APH-2
in vivo
results in increased viral replication and proviral loads, suggesting that HBZ and APH-2 modulate the virus and cellular pathways differently. Herein, we examined the effect of APH-2 on several known HBZ-modulated pathways: NF-κB (p65) transactivation, transforming growth factor β (TGF-β) signaling, and interferon regulatory factor 1 (IRF-1) transactivation. Like HBZ, APH-2 has the ability to inhibit p65 transactivation. Conversely, HBZ and APH-2 have divergent effects on TGF-β signaling and IRF-1 transactivation. Quantitative PCR and protein half-life experiments revealed a substantial disparity between HBZ and APH-2 transcript levels and protein stability, respectively. Taken together, our data further elucidate the functional differences between HBZ and APH-2 and how these differences can have profound effects on the survival of infected cells and, ultimately, pathogenesis.

IMPORTANCE
Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that have distinct pathological outcomes in infected hosts. Functional comparisons of HTLV-1 and HTLV-2 proteins provide a better understanding about how HTLV-1 infection is associated with disease and HTLV-2 infection is not. The HTLV genome antisense-strand genes
hbz
and
aph-2
are often the only viral genes expressed in HTLV-infected T cells. Previously, our group found that HTLV-1 HBZ and HTLV-2 APH-2 had distinct effects
in vivo
and hypothesized that the differences in the interactions of HBZ and APH-2 with important cell signaling pathways dictate whether cells undergo proliferation, apoptosis, or senescence. Ultimately, these functional differences may affect how HTLV-1 causes disease but HTLV-2 generally does not. In the current study, we compared the effects of HBZ and APH-2 on several HTLV-relevant cellular pathways, including the TGF-β signaling, NF-κB activation, and IRF-1 transactivation pathways.