bluuebunny/crossref_metadata_2025 huggingface dataset:
Space Perception, Visual Dissonance and the Fate of Standard Representationalism
Authors: Masrour Farid
Published: March 2016

This paper argues that a common form of representationalism has trouble accommodating empirical findings about visual space perception. Vision science tells us that the visual system systematically gives rise to different experiences of the same spatial property. This, combined with a naturalistic account of content, suggests that the same spatial property can have different veridical looks. I use this to argue that a common form of representationalism about spatial experience must be rejected. I conclude by considering alternatives to this view.
Nitrogen remobilization and conservation, and underlying senescence‐associated gene expression in the perennial switchgrass Panicum virgatum
Authors: Yang Jiading , Worley Eric , Ma Qin , Li Jun , Torres‐Jerez Ivone , Li Gaoyang , Zhao Patrick X. , Xu Ying , Tang Yuhong , Udvardi Michael
Published: March 2016

Improving nitrogen (N) remobilization from aboveground to underground organs during yearly shoot senescence is an important goal for sustainable production of switchgrass (Panicum virgatum) as a biofuel crop. Little is known about the genetic control of senescence and N use efficiency in perennial grasses such as switchgrass, which limits our ability to improve the process.

Switchgrass aboveground organs (leaves, stems and inflorescences) and underground organs (crowns and roots) were harvested every month over a 3‐yr period. Transcriptome analysis was performed to identify genes differentially expressed in various organs during development.

Total N content in aboveground organs increased from spring until the end of summer, then decreased concomitant with senescence, while N content in underground organs exhibited an increase roughly matching the decrease in shoot N during fall. Hundreds of senescence‐associated genes were identified in leaves and stems. Functional grouping indicated that regulation of transcription and protein degradation play important roles in shoot senescence. Coexpression networks predict important roles for five switchgrass NAC (NAM, ATAF1,2, CUC2) transcription factors (TFs) and other TF family members in orchestrating metabolism of carbohydrates, N and lipids, protein modification/degradation, and transport processes during senescence.

This study establishes a molecular basis for understanding and enhancing N remobilization and conservation in switchgrass.
A Comparison of the Sensitivity of Brush Allodynia and Semmes–Weinstein Monofilament Testing in the Detection of Allodynia Within Regions of Secondary Hyperalgesia in Humans
Authors: Maracle Emmalee C. , Hung Laurie Y. , Fell Sabrina I. , Osmond Michael R. , Brown Stephen H. M. , Srbely John Z.
Published: March 2016

Background

Two of the most common Quantitative Sensory Techniques (QST) employed to detect allodynia include mechanical brush allodynia and Semmes–Weinstein monofilaments. However, their relative sensitivity at detecting allodynia is poorly understood. The purpose of this study was to compare the sensitivity of brush allodynia against Semmes–Weinstein monofilament technique for detecting allodynia within regions of secondary hyperalgesia in humans.

Methods

Twenty subjects (10 males, 10 females; 21.1 ± 0.9 years) were recruited and randomly allocated to allodynia or monofilament groups. Topical capsaicin (Zostrix 0.075%) was applied to a target region defined by C4–C7 dermatomes. Allodynia testing was performed at 0‐ (baseline) and 10 minutes postcapsaicin. The Semmes–Weinstein group assessed changes in skin sensitivity 8 cm inferior to target region and 2 cm lateral to the spinous process, while brush allodynia was employed to detect the point inferior to the target region where subjects reported changes in skin sensitivity. The distance (cm) from this point to the inferior border of the target region was termed the Allodynia Score.

Results

Statistically significant increases in the Allodynia Score were observed at 10 minutes postcapsaicin compared to baseline (P < 0.001). No differences in monofilament scores were observed between 10 minutes postcapsaicin and baseline (P = 0.125). Brush allodynia also demonstrated superior sensitivity, detecting allodynia in 100% of cases compared to 60% in the Semmes–Weinstein group.

Conclusion

Brush allodynia is more sensitive than Semmes–Weinstein monofilaments for detecting mechanical allodynia in regions of secondary hyperalgesia. Brush allodynia may be preferred over Semmes–Weinstein monofilaments for clinical applications requiring reliable detection of allodynia.
Pigment Loss in Patients with Large Congenital Melanocytic Nevi: Various Clinical Presentations Documented in a Large Series
Authors: Polat Ekinci Algün , Kiliç Sila , Baykal Can
Published: March 2016

Background/Objectives

The association between vitiligo and congenital melanocytic nevi remains incompletely understood. The objective of this study was to investigate the frequency of depigmentation, including vitiligo, in patients with a large congenital melanocytic nevus (LCMN), which is a rare melanocytic tumor variant.

Methods

We retrospectively reviewed the files of 92 patients with an LCMN, including photographic documentation regarding the presence of pigment loss on the nevus mass, around the nevus, around the satellites, and elsewhere on the body.

Results

Depigmentation was observed in 8 (8.7%) of 92 patients with an LCMN. Depigmented areas within the main nevus mass were observed in six patients, and adjacent or remote vitiligo was observed in four patients. One patient also demonstrated halo depigmentation around some satellite nevi.

Conclusion

The coexistence of an LCMN with vitiligo does not appear to be rare and may occur with a spectrum of clinical presentations.
Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus
Authors: Badr Dana , Abadi Rami , Kurban Mazen , Abbas Ossama
Published: March 2016

Background/Objectives

In addition to several infectious and neoplastic cutaneous entities, plasmacytoid dendritic cells (pDCs) have been shown to be involved in the pathogenesis of multiple cutaneous inflammatory and autoimmune disorders, including those characterized histologically by an “interface dermatitis” pattern such as lupus or lichen planus (LP), but their role in lichen striatus (LS), which is also known to have this histologic inflammatory pattern, has never been studied. The objective of the study was to investigate the role of pDCs in LS.

Methods

Fifteen LS patients were found in our database and were immunohistochemically tested for pDC occurrence and activity using anti‐blood‐derived dendritic cell antigen‐2 and anti‐myxovirus resistance protein A (MxA) antibodies, respectively. These individuals were also compared with 15 individuals with LP.

Results

pDCs were present in all individuals with LS and LP, but they were less abundant in those with LS, although MxA (surrogate marker of local type I interferon production and thus an indirect assessment of pDC activity) was similarly intense and diffuse in all individuals with LS and LP. In addition to being part of the upper dermal inflammatory bandlike infiltrate as in LP, LS cases, unlike LP, also showed perieccrine pDCs.

Conclusions

pDCs constitute a central component of the inflammatory infiltrate in LS, suggesting a significant role in its pathogenesis. pDC distribution (perieccrine distribution) could also help in microscopically differentiating LS from LP.
An Average Error‐Ellipsoid Model for Evaluating TLS Point‐Cloud Accuracy
Authors: Chen Xijiang , Zhang Guang , Hua Xianghong , Xuan Wei
Published: March 2016

Estimation of the accuracy of terrestrial laser scanning has become a topical research issue. Point‐cloud accuracy should be clearly differentiated from the accuracy of individual points, as it is influenced by positional errors and adjacent error spaces. Furthermore, it cannot be determined by the sum of positional errors. In this paper it is proposed that the average error‐ellipsoid model is favourable for evaluating the accuracy of point clouds. Central to this model is the computation of the overlap between adjacent error ellipsoids and the determination of a functional relationship between the average volume of error ellipsoids and the point‐cloud accuracy. This paper outlines the key advantages of the proposed evaluation model, such as the capability of providing an estimate of local point‐cloud accuracy. The effectiveness of the model is discussed using a validation experiment.
The utilization and mode of action of organic acids in the feeds of cultured aquatic animals
Authors: Ng Wing‐Keong , Koh Chik‐Boon
Published: March 2016

The use of antibiotics in the feeds of cultured aquatic animals to mitigate infectious diseases or to boost growth performance is commonly practised. In recent years, the prophylactic use of antibiotics has been criticized which eventually led to their ban in animal production by many countries. In view of the current restrictions on antibiotic use, there is a critical need to evaluate alternatives. One potential substitute for antibiotic growth promoters in aquafeeds is organic acids and/or their respective salts. The use of dietary organic acids in the culture of aquatic animals has been the focus of much research and commercial interest recently. This review provides a comprehensive compilation of the current knowledge on the use of organic acids in aquafeeds, with emphasis on its impacts on growth, nutrient utilization, mineral availability, gut microbiota and disease resistance. Many studies have reported that some organic acids can significantly enhance the growth performance and health status of fish. Contradictory results have also been reported, which seems to depend on the aquatic animal species, type and concentrations of organic acids and the culture conditions used. Recent research indicating the beneficial impact of dietary organic acids on shrimp growth and health is highlighted. Possible mechanisms of action of these functional feed additives are discussed. Strategies for enhancing the effectiveness of dietary organic acids are given. This review aims to contribute to the sustainability of global aquaculture production by providing a viable alternative to harmful antibiotics, thereby meeting the growing consumer demand for antibiotic‐free seafood products.
Can the Genetic Origin Affect Rabbit Seminal Plasma Protein Profile along the Year?
Authors: Casares‐Crespo L , Talaván AM , Viudes‐de‐Castro MP
Published: March 2016

Contents

The study was designed to evaluate the influence of genetic origin on rabbit seminal plasma protein profile variation along the year. Seminal plasma of rabbits from line A (maternal line) and R (paternal line) collected during a natural year was subjected to polyacrylamide gel electrophoresis (SDS‐PAGE). The electrophoretic profile of rabbit seminal plasma resulted in multiple protein bands of different intensity ranging from 9 to 240 kDa. Results showed that seven protein bands were significantly different between genetic lines, and among these, three protein bands were significantly different between seasons. The differentially expressed proteins were identified by MALDI‐TOF/TOF or LC‐MS/MS analysis and were the following ones: FAM115E‐like (220, 113 and 59 kDa), ectonucleoside triphosphate diphosphohydrolase 3 isoform X2 (72 kDa), annexin A5 (32 kDa), lipocalin allergen Ory c 4 precursor (19 kDa), and haemoglobin subunit zetalike (13 kDa) between genetic lines and FAM115E‐like (113 kDa), haemoglobin subunit zetalike (13 kDa) and β‐nerve growth factor (12 kDa) between seasons. These results indicate that proteins from rabbit seminal plasma are under both seasonal control and genetic control. Furthermore, the differential presence of these proteins could be one of the causes explaining the differences observed in fertility and seminal parameters between these two lines in earlier studies.
Hume and the Problem of Paternalism: When is Humanity Sufficient?
Authors: Pollock Ryan
Published: March 2016

Abtract

Hume states that if a group of powerless, rational creatures lived amongst human beings, then humans would be required to treat this species with humanity but not with justice. Michael Ridge has argued that this implies humans would be required to engage in a morally dubious form of paternalism toward this imagined species. I argue that a proper understanding of why this imagined species is excluded from the scope of justice shows Hume has a plausible moral reason for requiring paternalism in this instance. The reason the imagined species is excluded is that they are incapable of feeling what I term “the pain of dependence,” or unease arising from complete dependence upon those who are more powerful. Those capable of the pain of dependence will have reason to resent exclusion from the scope of justice (and the accompanying susceptibility to paternalism). However, I contend that Hume did not think that the imagined species was capable of feeling the pain of dependence. This means that the imagined species would not consider themselves wronged when subject to paternalistic treatment, and, consequently, there is good reason to think the sort of paternalism that Hume's theory allows is not morally objectionable.
The Temporal Dynamics of Surprise
Authors: Noordewier Marret K. , Topolinski Sascha , Van Dijk Eric
Published: March 2016

Guided by a temporal dynamics perspective, we review and integrate theories and empirical evidence on surprise. We conceptualize surprise as the initial response to unexpected events, which should be differentiated from subsequent states that occur after people had time to make sense of the unexpected outcome. To understand the nature of surprise, it is therefore important to take time into account. Following this, a review of immediate cognitive correlates of surprise shows that irrespective of the valence of the outcome, the initial responses are the same. Moreover, the temporal dynamics perspective reconciles seemingly contradictory findings regarding the valence of surprise, such that studies that focus on surprise while it happens (initial interruption) support the notion that it feels relatively negative, whereas studies that focus on states after cognitive mastering show that subsequent experiential states depend on the valence of the outcome.
Experience‐Dependent Brain Development as a Key to Understanding the Language System
Authors: Westermann Gert
Published: March 2016

An influential view of the nature of the language system is that of an evolved biological system in which a set of rules is combined with a lexicon that contains the words of the language together with a representation of their context. Alternative views, usually based on connectionist modeling, attempt to explain the structure of language on the basis of complex associative processes. Here, I put forward a third view that stresses experience‐dependent structural development of the brain circuits supporting language as a core principle of the organization of the language system. In this view, embodied in a recent neuroconstructivist neural network of past tense development and processing, initial domain‐general predispositions enable the development of functionally specialized brain structures through interactions between experience‐dependent brain development and statistical learning in a structured environment. Together, these processes shape a biological adult language system that appears to separate into distinct mechanism for processing rules and exceptions, whereas in reality those subsystems co‐develop and interact closely. This view puts experience‐dependent brain development in response to a specific language environment at the heart of understanding not only language development but adult language processing as well.
Effect of storage time and donor sex of transfused red blood cells on 1‐year survival in patients undergoing cardiac surgery: an observational study
Authors: Desmarets Maxime , Bardiaux Laurent , Benzenine Eric , Dussaucy Alain , Binda Delphine , Tiberghien Pierre , Quantin Catherine , Monnet Elisabeth
Published: March 2016

BACKGROUND

Red blood cell (RBC) storage lesions and RBCs from females transfused into male recipients may have adverse effects on transfusion recipients' survival. We hypothesized that the effect of donor sex and the effect of age of blood on mortality would be most apparent in cardiac surgery patients.

STUDY DESIGN AND METHODS

Using data from French Blood Services and two university hospitals, we conducted a retrospective cohort study on cardiac surgery patients whose first transfusion occurred between 2007 and 2011. The age of blood and donor sex effects on 1‐year survival were studied using Cox regression modeling, with time‐dependent stratification on the number of RBCs and adjustments for the type of surgery and other products transfused.

RESULTS

Among the 2715 cardiac surgery patients, 85.1% were alive after 1 year. Age of blood and donor sex were associated with survival before adjustments (p < 0.0001). However, the adjusted hazard ratios (HRs) for patients transfused with blood stored for 29 days or more versus 14 days or less were 0.97 (95% confidence interval [95% CI], 0.69‐1.35; p = 0.98) and 1.22 (95% CI, 0.81‐1.82) for patients who received only sex‐mismatched RBCs versus all matched units (p = 0.27). For males transfused solely with female RBCs, the HR was 0.96 (95% CI, 0.57‐1.61; p = 0.69); in females transfused only with male RBCs, it was 2.03 (95% CI, 0.87‐4.73; p = 0.17).

CONCLUSIONS

In this first study of survival after transfusion in France, there was no significant effect for age of blood or donor sex. Contrary to previously reported data, female RBCs appear to be safe for male recipients.
Non‐destructive imaging to describe a new species of Obama land planarian (Platyhelminthes, Tricladida)
Authors: Carbayo Fernando , Francoy Tiago M. , Giribet Gonzalo
Published: March 2016

The land planarians in the genus Obama include the largest species of the Neotropical Geoplaninae. Morphological discrimination of Obama species can be difficult, as many species are morphologically similar and some present asymmetric – difficult to interpret – copulatory organs. New techniques are thus welcomed to provide faster species description and identification. Here, we study several specimens of Obama by means of mainly 2D and 3D μCT‐based images obtained through X‐ray microcomputed tomography (μCT) of a paratype, and, complementarily, histological sections of the holotype and a second paratype, which were digitized into virtual slides. Comparison of these images with traditional histological sections and descriptions of the known species of the genus allows us to conclude that our specimens constitute a new species, which we describe here. We further evaluate the phylogenetic placement of the new species using gene fragments from the mitochondrial cytochrome c oxidase subunit I and the nuclear elongation factor‐1α. Raw and derivative μCT data and virtual histological sections were deposited in an open repository (GigaDB) and are freely available. This work leads us to conclude that μCT constitutes a relatively fast, inexpensive non‐destructive method that produces results comparable to those of traditional histology, and is thus amenable for describing flatworm species.
Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation
Authors: Uphoff Stephan , Lord Nathan D. , Okumus Burak , Potvin-Trottier Laurent , Sherratt David J. , Paulsson Johan
Published: March 2016

To have or have not determines DNA repair

Cells presumably try to protect DNA from damage at all costs. But Uphof
et al.
show that they do not, because the cost is too high. Single-molecule and single-cell measurements show that the DNA repair enzyme Ada, which also regulates its own expression, was present in such low amounts in
E. coli
that stochastic variation led to some cells having none of the protein at all. Such cells undergo increased mutagenesis, which could be beneficial in circumstances in which increased genetic heterogeneity is required for adaptation. The expression of large amounts of such a DNA-altering protein was also toxic.

Science
, this issue p.
1094
Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection
Authors: Winkelman Jared T. , Vvedenskaya Irina O. , Zhang Yuanchao , Zhang Yu , Bird Jeremy G. , Taylor Deanne M. , Gourse Richard L. , Ebright Richard H. , Nickels Bryce E.
Published: March 2016

Choosing where to start transcription

The RNA polymerase enzyme complex binds to the promoter of a gene and separates the two DNA strands. The subsequently formed “transcription bubble” is required for RNA synthesis to begin. How RNA polymerase chooses the exact DNA base at which it will start transcription has been unclear. Winkelman
et al.
show that a control element upstream of the start site is involved in helping RNA polymerase make this choice in bacteria. Start site selection involves promoter scrunching, where a stationary RNA polymerase unwinds and pulls DNA through the active site, scrunching the DNA of the transcription bubble.

Science
, this issue p.
1090
Response to Comment on “Estimating the reproducibility of psychological science”
Authors: Anderson Christopher J. , Bahník Štěpán , Barnett-Cowan Michael , Bosco Frank A. , Chandler Jesse , Chartier Christopher R. , Cheung Felix , Christopherson Cody D. , Cordes Andreas , Cremata Edward J. , Della Penna Nicolas , Estel Vivien , Fedor Anna , Fitneva Stanka A. , Frank Michael C. , Grange James A. , Hartshorne Joshua K. , Hasselman Fred , Henninger Felix , van der Hulst Marije , Jonas Kai J. , Lai Calvin K. , Levitan Carmel A. , Miller Jeremy K. , Moore Katherine S. , Meixner Johannes M. , Munafò Marcus R. , Neijenhuijs Koen I. , Nilsonne Gustav , Nosek Brian A. , Plessow Franziska , Prenoveau Jason M. , Ricker Ashley A. , Schmidt Kathleen , Spies Jeffrey R. , Stieger Stefan , Strohminger Nina , Sullivan Gavin B. , van Aert Robbie C. M. , van Assen Marcel A. L. M. , Vanpaemel Wolf , Vianello Michelangelo , Voracek Martin , Zuni Kellylynn
Published: March 2016

Gilbert
et al
. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
Realization of a scalable Shor algorithm
Authors: Monz Thomas , Nigg Daniel , Martinez Esteban A. , Brandl Matthias F. , Schindler Philipp , Rines Richard , Wang Shannon X. , Chuang Isaac L. , Blatt Rainer
Published: March 2016

Reducing quantum overhead

A quantum computer is expected to outperform its classical counterpart in certain tasks. One such task is the factorization of large integers, the technology that underpins the security of bank cards and online privacy. Using a small-scale quantum computer comprising five trapped calcium ions, Monz
et al.
implement a scalable version of Shor's factorization algorithm. With the function of ions being recycled and the architecture scalable, the process is more efficient than previous implementations. The approach thus provides the potential for designing a powerful quantum computer, but with fewer resources.

Science
, this issue p.
1068
A copy-and-paste gene regulatory network
Authors: Lynch Vincent J.
Published: March 2016

Transposable elements provide a ready-made route to regulate complex gene networks

[Also see Report by

Chuong
et al.

]
Surprised by selectivity
Authors: de Jong Krijn P.
Published: March 2016

A bifunctional catalyst enables olefin synthesis from carbon monoxide and hydrogen at high selectivity

[Also see Report by

Jiao
et al.

]
Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit
Authors: Desoubeaux Guillaume , Dominique Manon , Morio Florent , Thepault Rose-Anne , Franck-Martel Claire , Tellier Anne-Charlotte , Ferrandière Martine , Hennequin Christophe , Bernard Louis , Salamé Ephrem , Bailly Éric , Chandenier Jacques
Published: March 2016

Over a 5-month period, four liver transplant patients at a single hospital were diagnosed with
Pneumocystis jirovecii
pneumonia (PCP). This unusually high incidence was investigated using molecular genotyping. Bronchoalveolar lavage fluids (BALF) obtained from the four liver recipients diagnosed with PCP were processed for multilocus sequence typing (MLST) at three loci (
SOD
, mt26s, and
CYB
). Twenty-four other BALF samples, which were positive for
P. jirovecii
and collected from 24 epidemiologically unrelated patients with clinical signs of PCP, were studied in parallel by use of the same method.
Pneumocystis jirovecii
isolates from the four liver recipients all had the same genotype, which was different from those of the isolates from all the epidemiologically unrelated individuals studied. These findings supported the hypothesis of a common source of contamination or even cross-transmission of a single
P. jirovecii
clone between the four liver recipients. Hospitalization mapping showed several possible encounters between these four patients, including outpatient consultations on one particular date when they all possibly met. This study demonstrates the value of molecular genotyping of
P. jirovecii
isolated from clinical samples for epidemiological investigation of PCP outbreaks. It is also the first description of a common source of exposure to a single
P. jirovecii
clone between liver transplant recipients and highlights the importance of prophylaxis in such a population.
Microbiology Learning and Education Online
Authors: Guarner Jeannette , Niño Silvia M.
Published: March 2016

The ubiquity of devices that connect to the Internet has exploded, allowing for easy dissemination of information. Many teachers from kindergarten to universities use the information obtained online or post material they want their students to access. Online media readily places articles, books, videos, and games at our fingertips. The public in general also gathers health information from the Internet. The following review will explore what has been published regarding microbiology education and learning online and the use of electronic media by microbiologists for scientific purposes.
Coordinated Neutralization and Immune Activation by the Cytosolic Antibody Receptor TRIM21
Authors: Fletcher Adam J. , James Leo C.
Published: March 2016

TRIM21 is a high-affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. Here we summarize its role in extending antibody protection into the intracellular environment and allowing nonprofessional cells to benefit from adaptive immunity. We highlight recent work that has shed light on how TRIM21 acts as both an immune sensor and effector. We also review how TRIM21 synergizes with other innate immune receptors to promote an integrated antiviral response.
PrPSc-Specific Antibody Reveals C-Terminal Conformational Differences between Prion Strains
Authors: Saijo Eri , Hughson Andrew G. , Raymond Gregory J. , Suzuki Akio , Horiuchi Motohiro , Caughey Byron
Published: March 2016

Understanding the structure of PrPScand its strain variation has been one of the major challenges in prion disease biology. To study the strain-dependent conformations of PrPSc, we purified proteinase-resistant PrPSc(PrPRES) from mouse brains with three different murine-adapted scrapie strains (Chandler, 22L, and Me7) and systematically tested the accessibility of epitopes of a wide range of anti-PrP and anti-PrPScspecific antibodies by indirect enzyme-linked immunosorbent assay (ELISA). We found that epitopes of most anti-PrP antibodies were hidden in the folded structure of PrPRES, even though these epitopes are revealed with guanidine denaturation. However, reactivities to a PrPSc-specific conformational C-terminal antibody showed significant differences among the three different prion strains. Our results provide evidence for strain-dependent conformational variation near the C termini of molecules within PrPScmultimers.

IMPORTANCEIt has long been apparent that prion strains can have different conformations near the N terminus of the PrPScprotease-resistant core. Here, we show that a C-terminal conformational PrPSc-specific antibody reacts differently to three murine-adapted scrapie strains. These results suggest, in turn, that conformational differences in the C terminus of PrPScalso contribute to the phenotypic distinction between prion strains.
Derivation and Characterization of a CD4-Independent, Non-CD4-Tropic Simian Immunodeficiency Virus
Authors: Swanstrom Adrienne E. , Haggarty Beth , Jordan Andrea P. O. , Romano Josephine , Leslie George J. , Aye Pyone P. , Marx Preston A. , Lackner Andrew A. , Del Prete Gregory Q. , Robinson James E. , Betts Michael R. , Montefiori David C. , LaBranche Celia C. , Hoxie James A.
Published: March 2016

CD4 tropism is conserved among all primate lentiviruses and likely contributes to viral pathogenesis by targeting cells that are critical for adaptive antiviral immune responses. Although CD4-independent variants of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have been described that can utilize the coreceptor CCR5 or CXCR4 in the absence of CD4, these viruses typically retain their CD4 binding sites and still can interact with CD4. We describe the derivation of a novel CD4-independent variant of pathogenic SIVmac239, termed iMac239, that was used to derive an infectious R5-tropic SIV lacking a CD4 binding site. Of the seven mutations that differentiate iMac239 from wild-type SIVmac239, a single change (D178G) in the V1/V2 region was sufficient to confer CD4 independence in cell-cell fusion assays, although other mutations were required for replication competence. Like other CD4-independent viruses, iMac239 was highly neutralization sensitive, although mutations were identified that could confer CD4-independent infection without increasing its neutralization sensitivity. Strikingly, iMac239 retained the ability to replicate in cell lines and primary cells even when its CD4 binding site had been ablated by deletion of a highly conserved aspartic acid at position 385, which, for HIV-1, plays a critical role in CD4 binding. iMac239, with and without the D385 deletion, exhibited an expanded host range in primary rhesus peripheral blood mononuclear cells that included CCR5
+
CD8
+
T cells. As the first non-CD4-tropic SIV, iMac239-ΔD385 will afford the opportunity to directly assess the
in vivo
role of CD4 targeting on pathogenesis and host immune responses.

IMPORTANCE
CD4 tropism is an invariant feature of primate lentiviruses and likely plays a key role in pathogenesis by focusing viral infection onto cells that mediate adaptive immune responses and in protecting virions attached to cells from neutralizing antibodies. Although CD4-independent viruses are well described for HIV and SIV, these viruses characteristically retain their CD4 binding site and can engage CD4 if available. We derived a novel CD4-independent, CCR5-tropic variant of the pathogenic molecular clone SIVmac239, termed iMac239. The genetic determinants of iMac239's CD4 independence provide new insights into mechanisms that underlie this phenotype. This virus remained replication competent even after its CD4 binding site had been ablated by mutagenesis. As the first truly non-CD4-tropic SIV, lacking the capacity to interact with CD4, iMac239 will provide the unique opportunity to evaluate SIV pathogenesis and host immune responses in the absence of the immunomodulatory effects of CD4
+
T cell targeting and infection.
The Vaccinia Virus H3 Envelope Protein, a Major Target of Neutralizing Antibodies, Exhibits a Glycosyltransferase Fold and Binds UDP-Glucose
Authors: Singh Kavita , Gittis Apostolos G. , Gitti Rossitza K. , Ostazeski Stanley A. , Su Hua-Poo , Garboczi David N.
Published: March 2016

The highly conserved H3 poxvirus protein is a major target of the human antibody response against poxviruses and is likely a key contributor to protection against infection. Here, we present the crystal structure of H3 from vaccinia virus at a 1.9-Å resolution. H3 looks like a glycosyltransferase, a family of enzymes that transfer carbohydrate molecules to a variety of acceptor substrates. Like glycosyltransferases, H3 binds UDP-glucose, as shown by saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, and this binding requires Mg
2+
. Mutation of the glycosyltransferase-like metal ion binding motif in H3 greatly diminished its binding to UDP-glucose. We found by flow cytometry that H3 binds to the surface of human cells but does not bind well to cells that are deficient in surface glycosaminoglycans. STD NMR experiments using a heparin sulfate decasaccharide confirmed that H3 binds heparin sulfate. We propose that a surface of H3 with an excess positive charge may be the binding site for heparin. Heparin binding and glycosyltransferase activity may be involved in the function of H3 in the poxvirus life cycle.

IMPORTANCE
Poxviruses are under intense research because of bioterrorism concerns, zoonotic infections, and the side effects of existing smallpox vaccines. The smallpox vaccine using vaccinia virus has been highly successful, but it is still unclear why the vaccine is so effective. Studying the antigens that the immune system recognizes may allow a better understanding of how the vaccine elicits immunity and how improved vaccines can be developed. Poxvirus protein H3 is a major target of the immune system. The H3 crystal structure shows that it has a glycosyltransferase protein fold. We demonstrate that H3 binds the sugar nucleotide UDP-glucose, as do glycosyltransferases. Our experiments also reveal that H3 binds cell surface molecules that are involved in the attachment of poxviruses to cells. These structural and functional studies of H3 will help in designing better vaccines and therapeutics.
Upregulation of the Adhesin Gene
EPA1
Mediated by
PDR1
in Candida glabrata Leads to Enhanced Host Colonization
Authors: Vale-Silva Luis A. , Moeckli Beat , Torelli Riccardo , Posteraro Brunella , Sanguinetti Maurizio , Sanglard Dominique
Published: March 2016

Candida glabrata
is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator
PDR1
, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in
C. glabrata
with increased virulence in animal models and also with increased adherence to specific host cell types. The
C. glabrata
adhesin gene
EPA1
is a major contributor of virulence and adherence to host cells. Here, we show that
EPA1
expression is controlled by
PDR1
independently of subtelomeric silencing, a known
EPA1
regulation mechanism. Thus, a relationship exists between
PDR1
,
EPA1
expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for
C. glabrata
in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of
C. glabrata
infections in human patients.
A Gammaherpesvirus Noncoding RNA Is Essential for Hematogenous Dissemination and Establishment of Peripheral Latency
Authors: Feldman Emily R. , Kara Mehmet , Oko Lauren M. , Grau Katrina R. , Krueger Brian J. , Zhang Junjie , Feng Pinghui , van Dyk Linda F. , Renne Rolf , Tibbetts Scott A.
Published: March 2016

Noncoding RNAs (ncRNAs) represent an intriguing and diverse class of molecules that are now recognized for their participation in a wide array of cellular processes. Viruses from multiple families have evolved to encode their own such regulatory RNAs; however, the specific
in vivo
functions of these ncRNAs are largely unknown. Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are ubiquitous human pathogens that are associated with the development of numerous malignancies. Like EBV and KSHV, murine gammaherpesvirus 68 (MHV68) establishes lifelong latency in B cells and is associated with lymphomagenesis. The work described here reveals that the MHV68 ncRNA TMER4 acts at a critical bottleneck in local lymph nodes to facilitate hematogenous dissemination of the virus and establishment of latency at peripheral sites.
How do authors of systematic reviews deal with research malpractice and misconduct in original studies? A cross-sectional analysis of systematic reviews and survey of their authors
Authors: Elia Nadia , von Elm Erik , Chatagner Alexandra , Pöpping Daniel M , Tramèr Martin R
Published: March 2016

Objectives

To study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct.

Design

Cross-sectional analysis of systematic reviews and survey of their authors.

Participants

118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and theCochrane Library, in 2013.

Main outcomes and measures

Number (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors’ and (5) authors’ conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals.

Results

80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals.

Conclusions

Only half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.
Measuring health and performance in preweaning dairy calves
Authors: Sherwin Virginia , Hudson Chris , Henderson Andrew , Breen James
Published: March 2016

The main aim of calf rearing is to produce a healthy calf that is achieving the target growth rate. Calf mortality rate and daily liveweight gain represent appropriate bottom‐line ‘output’ measures for evaluating the success of a calf‐rearing programme, and they are affected by various ‘inputs’ or aspects of the calf‐rearing process. This article summarises how these outputs can be monitored, and highlights how some key input areas can be assessed when output targets are not met.
Osteomyelitis and fracture callus abscessation secondary to a foreign body reaction in a traumatic open fracture of the zygomatic bone of a puppy
Authors: Delisser Peter J , Warren‐Smith Chris
Published: March 2016

A five‐month‐old male labrador retriever presented with a large (6×3×5 cm) firm swelling associated with the right zygomatic arch. The dog suffered a bite wound two months previously, causing puncture wounds dorsal to the orbit where radiographs demonstrated a minimally displaced fracture of the zygomatic arch and surrounding soft, fluctuant swelling. Following three to four weeks of conservative management, the swelling had partially ossified. CT of the skull demonstrated a large cavitary osseous lesion of the right zygomatic arch associated with the previous fracture site. A lateral approach was used to perform marginal excision of the mass, preserving the eye. Histopathology of the mass revealed woven bone formation, granulation tissue lining the cavity and a fragment of plant material within the cavity. The recovery from surgery was unremarkable, and the dog did not suffer any intraoperative or postoperative complications. The dog was clinically normal at follow‐up 21 months post surgery.
Brown Creeper (Certhia americana) demographic response to hardwood forests managed under the selection system
Authors: Geleynse Daniel M. , Nol Erica , Burke Dawn M. , Elliott Ken A.
Published: March 2016

The Brown Creeper (Certhia americana Bonaparte, 1838) has been identified as one of the most sensitive passerines to partial forest harvest in North America. The effect of selection logging on Brown Creeper density, nest timing, nest survival, and nest and foraging site selection was examined in five silviculture treatments (intensive group selection, typical group selection, old single-tree selection, recent single-tree selection, and control forests) of Algonquin Provincial Park, Canada. As Brown Creeper nests under the bark of large, decaying trees, we hypothesized that Brown Creeper density, timing of breeding, nest survival, and nest and foraging site selection would be negatively affected by silviculture through the removal of large, decaying trees as part of providing safe conditions for loggers. We monitored 101 nests of Brown Creeper during the 2010 and 2011 breeding seasons, mapped territories to estimate density, and conducted foraging surveys. Brown Creeper density was reduced by about 42% in logged stands compared with control stands. Despite that, silviculture did not significantly alter timing of breeding or nest survival. However, the loss of large trees through partial harvesting meant that Brown Creeper nested closer to adjacent, small forested wetlands and often in balsam fir (Abies balsamea (L.) Mill.) in treated stands. In control stands, Brown Creeper nested further from forested wetlands, disproportionately in greater numbers in upland hardwoods, and preferentially in the bark of snags of yellow birch (Betula alleghaniensis Britton). The change in the species of tree used for nesting and the general forest type as a result of logging also resulted in consequences for the selection of foraging substrates. To maintain higher densities of Brown Creeper in logged stands in Algonquin Park, we recommend retaining larger diameter yellow birch, both snags and live trees, preferably within strategically located uncut reserves based on habitat supply planning, that maintains patches roughly the size of Brown Creeper territories (10 ha).
Lyapunov theorems for exponential dichotomies in Hilbert spaces
Authors: Dragičević Davor , Preda Ciprian
Published: March 2016

For a nonautonomous dynamics defined by a sequence of linear operators, we obtain a complete characterization of the notion of a uniform exponential dichotomy in terms of the existence of appropriate Lyapunov sequences. In sharp contrast to previous results, we consider the case of noninvertible dynamics, thus requiring only the invertibility of operators along the unstable direction. Furthermore, we deal with operators acting on an arbitrary Hilbert space. As a nontrivial application of our work, we study the persistence of uniform exponential behavior under small linear and nonlinear perturbations.
Valiron and Abel equations for holomorphic self-maps of the polydisc
Authors: Arosio Leandro , Gumenyuk Pavel
Published: March 2016

We introduce a notion of hyperbolicity and parabolicity for a holomorphic self-map [Formula: see text] of the polydisc which does not admit fixed points in [Formula: see text]. We generalize to the polydisc two classical one-variable results: we solve the Valiron equation for a hyperbolic [Formula: see text] and the Abel equation for a parabolic nonzero-step [Formula: see text]. This is done by studying the canonical Kobayashi hyperbolic semi-model of [Formula: see text] and by obtaining a normal form for the automorphisms of the polydisc. In the case of the Valiron equation, we also describe the space of all solutions.
Schwinger–Dyson approach and its application to generate a light composite scalar
Authors: Doff A. , Natale A. A.
Published: March 2016

We discuss the possibility of generating a light composite scalar boson, in a scenario that we may generically call Technicolor, or in any variation of a strongly interacting theory, where by light we mean a scalar composite mass about one order of magnitude below the characteristic scale of the strong theory. Instead of most of the studies about a composite Higgs boson, which are based on effective Lagrangians, we consider this problem in the framework of nonperturbative solutions of the fermionic Schwinger–Dyson and Bethe–Salpeter equations. We study a range of mechanisms proposed during the recent years to form such light composite boson, and verify that such possibility seems to be necessarily associated to a fermionic self-energy that decreases slowly with the momentum.
Effects of Y2O3insertion layer on anisotropic magnetoresistance of Ni81Fe19 films
Authors: Wang Shuyun , Huang Huaxue , Sun Yang , Gao Tiejun , He Yuan
Published: March 2016

A series of Ta(4 nm)/Y2O[Formula: see text]/Ni[Formula: see text]Fe[Formula: see text](20 nm)/Y2O[Formula: see text]/Ta(3 nm) films were prepared on glass substrates by magnetron sputtering under appropriate conditions. AMR value, phase composition and magnetic hysteresis hoop of Ni[Formula: see text]Fe[Formula: see text] films were measured and analyzed by four-point probe technology, X-ray diffraction (XRD) and vibrating sample magnetometer (VSM), respectively. Influence of Y2O3which work as oxidation intercalation on AMR values of Ni[Formula: see text]Fe[Formula: see text] films was investigated. The experiment results show that, at the substrate temperature of 450[Formula: see text]C, the AMR value of the film with Y2O3layer thickness of 2.5 nm can reach 4.61%, increasing by 71.3% compares with the film without Y2O3layer.
Thermal effect and the passively Q-switching characteristics based on the composite YVO4/Nd:YVO4 laser at 1342 nm
Authors: Gao Shang
Published: March 2016

Passively Q-switching performance of the composite Nd:YVO4 laser was experimentally investigated by using V:YAG as saturable absorber. The comparisons between the temperature distributions and thermal focal lengths in Nd:YVO4 crystals were numerically analyzed by using a finite element method. The maximum CW output power of 1.65 W with an optical slope efficiency of 25.6% was obtained by YVO4/Nd:YVO4 composite crystal under an incident pump power of 7.1 W. For Q-switching regime, the highest output power was 664 mW with a pulse repetition rate of 30 kHz and pulse duration of 35 ns.