bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic architecture of amylose biosynthesis in maize kernel
Authors: Li Changsheng , Huang Yongcai , Huang Ruidong , Wu Yongrui , Wang Wenqin 
Published: August 2017

SummaryStarch is the most abundant storage carbohydrate in maize kernel. The content of amylose and amylopectin confers unique properties in food processing and industrial application. Thus, the resurgent interest has been switched to the study of individual amylose or amylopectin rather than total starch, whereas the enzymatic machinery for amylose synthesis remains elusive. We took advantage of the phenotype of amylose content and the genotype of 9,007,194 single nucleotide polymorphisms from 464 inbred maize lines. The genome‐wide association study identified 27 associated loci involving 39 candidate genes that were linked to amylose content including transcription factors, glycosyltransferases, glycosidases, as well as hydrolases. Except the waxy gene that encodes the granule‐bound starch synthase, the remaining candidate genes were located in the upstream pathway of amylose synthesis, while the downstream members were already known from prior studies. The linked candidate genes could be transferred to manipulate amylose content and thus add value to maize kernel in the breeding programme.
Hookworm excretory/secretory products modulate immune responses to heterologous and species‐specific antigens
Authors: Diliani N. , Dondji B. 
Published: August 2017

SummaryApproximately one billion people are currently infected with hookworm. Despite its high prevalence and the concomitant immune suppression seen in infected individuals, little research has been performed on the mechanism of immunosuppression by hookworm. Our study focused on characterizing mechanisms utilized by hookworm to suppress the host immune response. Splenocytes and draining lymph node cells from mice injected with hookworm excretory/secretory (ES) proteins showed decreased proliferation in response to both heterologous and species‐specific antigens while also having increased nitric oxide secretion. Analysis by fluorescence‐activated cell sorting revealed that mice injected with ES had reduced percentages of CD4+ T cells indicating potential effects of ES proteins on lymphocyte homeostasis. Antibody and cytokine response analyses demonstrated that immunization with ES proteins decreased IgG and IgG1 levels, also decreased interleukin (IL‐)‐4 and increased IL‐12 and interferon‐gamma (IFN‐γ) cytokine production suggesting impairment of B‐cell activation and a shift towards a nonhealing IL‐12 directed T helper‐1 immune response. Together, these data demonstrate for the first time that host immunosuppression by hookworms is orchestrated by ES proteins and provide mechanisms underlying the shift towards a nonhealing Th‐1 profile as seen in humans suffering from hookworm infection.
Risk, Precaution, Responsibility, and Equal Concern
Authors: Herwig Alexia , Simoncini Marta 
Published: August 2017

AbstractSystemic risks are risks produced through interconnected non‐wrongful actions of individuals, in the sense that an individual's action is a negligible cause of the risk. Due to scale effects of interaction, their consequences can be serious but they are also difficult to predict and assess via a risk assessment. Since we can have good reason to engage in the interconnected activities giving rise to systemic risk, we incur a concurrent collective responsibility to ensure that the risks are fairly distributed and well regulated. James argues that fairness in this context requires taking reasonably available precautions ensuring for each risk‐bearer a favourable ratio of expected benefits over expected losses. In sections2and3we argue that such a conception of fairness applies but only on the condition that the systemic risks created are irreversible risks and that the general background conditions of justice are imperfectly fair. When risks are reversible, compensatory justice can correct for unfairness in risk imposition. Where risks are irreversible, compensatory justice necessarily fails, giving rise to a collective responsibility to regulate fairly ex ante. Additionally, where background conditions of justice are fully fair and the systemic risk is well understood, risk bearers can be said to have consented to the systemic risk. If they are not fair, we argue that the primary political obligation should lie in fixing the fairness of the backgrounds of justice. A related reason for addressing the general background conditions of fairness is that James’ account of fairness in systemic risk imposition encounters a baseline problem. If expected risks and benefits are calculated again an unfair historic background condition, systemic risk imposition would not be fully fair. Section4shows why differences in evidentiary uncertainty as to probability and levels of harm and effective responses require a normatively appropriate response in the form of additional precautions. We show that the evidentiary standards set for risk‐based cost‐benefit analysis have a connection with deontology because they express a postulate of equal treatment in formal terms. Systemic risks can have different possible degrees of epistemological certainty due to factors of social and natural origin, such as more available research funding or higher degrees of complexity for some systemic risks but not others. These differences have to be mitigated by taking even greater precautions in difficult‐to‐research systemic risks.
Predicting the Risk of Biological Invasions Using Environmental Similarity and Transport Network Connectedness
Authors: Cope Robert C. , Ross Joshua V. , Wittmann Talia A. , Watts Michael J. , Cassey Phillip 
Published: August 2017

AbstractUnderstanding the risk of biological invasions associated with particular transport pathways and source regions is critical for implementing effective biosecurity management. This may require both a model for physical connectedness between regions, and a measure of environmental similarity, so as to quantify the potential for a species to be transported from a given region and to survive at a destination region. We present an analysis of integrated biosecurity risk into Australia, based on flights and shipping data from each global geopolitical region, and an adaptation of the “range bagging” method to determine environmental matching between regions. Here, we describe global patterns of environmental matching and highlight those regions with many physical connections. We classify patterns of global invasion risk (high to low) into Australian states and territories. We validate our analysis by comparison with global presence data for 844 phytophagous insect pest species, and produce a list of high‐risk species not previously known to be present in Australia. We determined that, of the insect pest species used for validation, the species most likely to be present in Australia were those also present in geopolitical regions with high transport connectivity to Australia, and those regions that were geographically close, and had similar environments.
Statistical Inference Based on Randomly Generated Auxiliary Variables
Authors: Schouten Barry 
Published: August 2017

SummaryIn most real life studies, auxiliary variables are available and are employed to explain and understand missing data patterns and to evaluate and control causal relationships with variables of interest. Usually their availability is assumed to be a fact, even if the variables are measured without the objectives of the study in mind. As a result, inference with missing data and causal inference require some assumptions that cannot easily be validated or checked. In this paper, a framework is constructed in which auxiliary variables are treated as a selection, possibly random, from the universe of variables on a population. This framework provides conditions to make statistical inference beyond the traces of bias or effects found by the auxiliary variables themselves. The utility of the framework is demonstrated for the analysis and reduction of non-response in surveys. However, the framework may be more generally used to understand the strength of association between variables. Important roles are played by the diversity and diffusion of the population of interest, features that are defined in the paper and the estimation of which is discussed.
Effect of conjugated linoleic acids and omega‐3 fatty acids with or without resistance training on muscle mass in high‐fat diet‐fed middle‐aged mice
Authors: Lee Sang‐Rok , Khamoui Andy V. , Jo Edward , Zourdos Michael C. , Panton Lynn B. , Ormsbee Michael J. , Kim Jeong‐Su 
Published: August 2017

New Findings
What is the central question of this study?
This study examined the effects of 20 weeks of administration of conjugated linoleic acids/omega‐3 fatty acids with or without programed resistance exercise training on body composition, skeletal muscle properties and functional capacity in middle‐aged mice fed a high‐fat diet.

What is the main finding and its importance?
Chronic daily administration of conjugated linoleic acids/omega‐3 fatty acids with resistance exercise training can help to blunt fat gain, alleviate loss of myogenic capacity and sensorimotor function and lower tissue inflammation in middle‐aged mice during chronic high‐fat diet‐induced catabolism.

This study investigated the effects of 20 weeks of combined conjugated linoleic acid (CLA)/omega‐3 fatty acid (n‐3) administration independently or combined with resistance exercise training (RET) on skeletal muscle in middle‐aged mice consuming a high‐fat diet (HFD). Nine‐month‐old C57BL/6 mice were randomly assigned into four experimental groups (H, high‐fat diet; HE, H + RET; HCN, H + CLA/n‐3; and HECN, H + CLA/n3 + RET). Body composition and functional capacity were assessed pre‐ and post‐intervention. Muscle tissues were collected at 14 months of age. ANOVA was used, with significance set at P ≤ 0.05. Fat mass significantly increased in H (+74%), HE (+142%) and HECN (+43%) but not in HCN. Muscle wet weights were significantly lower in H and HCN than in HE and HECN. Grip strength substantially declined in H (−15%) and HCN (−17%), whereas sensorimotor function significantly declined only in H (−11%). HECN exhibited improvement in strength (+22%) and sensorimotor coordination (+17%). In comparison to H, muscle tumour necrosis factor‐α mRNA expression was significantly lower in HE (−39%), HCN (−24%) and HECN (−21%), respectively. Mean myofibre cross‐sectional areas were markedly lower in H and HCN than in HE and HECN. H showed significantly lower satellite cell abundance and numbers of myonuclei than all other groups. Our findings suggest that long‐term daily CLA/n‐3 intake with resistance training improved sensorimotor function, ameliorated fat gain and prevented loss of myogenic capacity while lowering tumour necrosis factor‐α expression during chronic HFD.
Potential of High-Affinity, Slow Off-Rate Modified Aptamer Reagents for Mycobacterium tuberculosis Proteins as Tools for Infection Models and Diagnostic Applications
Authors: Russell Theresa M. , Green Louis S. , Rice Taylor , Kruh-Garcia Nicole A. , Dobos Karen , De Groote Mary A. , Hraha Thomas , Sterling David G. , Janjic Nebojsa , Ochsner Urs A. 
Published: August 2017

ABSTRACT

Direct pathogen detection in blood to diagnose active tuberculosis (TB) has been difficult due to low levels of circulating antigens or due to the lack of specific, high-affinity binding reagents and reliable assays with adequate sensitivity. We sought to determine whether slow off-rate modified aptamer (SOMAmer) reagents with subnanomolar affinity for
Mycobacterium tuberculosis
proteins (antigens 85A, 85B, 85C, GroES, GroEL2, DnaK, CFP10, KAD, CFP2, RplL, and Tpx) could be useful to diagnose tuberculosis. When incorporated into the multiplexed, array-based proteomic SOMAscan assay, limits of detection reached the subpicomolar range in 40% serum. Binding to native
M. tuberculosis
proteins was confirmed by using
M. tuberculosis
culture filtrate proteins and fractions from infected macrophages and via affinity capture assays and subsequent mass spectrometry. Comparison of serum from culture-positive pulmonary TB patients and TB suspects systematically ruled out for TB revealed small but statistically significant (
P
< 0.0001) differences in the median
M. tuberculosis
signals and in specific pathogen markers, such as antigen 85B. Samples where many
M. tuberculosis
aptamers produced high signals were rare exceptions. In concentrated, protein-normalized urine from TB patients and non-TB controls, the CFP10 (EsxB) SOMAmer yielded the most significant differential signals (
P
< 0.0276), particularly in TB patients with HIV coinfection. In conclusion, direct
M. tuberculosis
antigen detection proved difficult even with a sensitive method such as SOMAscan, likely due to their very low, subpicomolar abundance. The observed differences between cases and controls had limited diagnostic utility in serum and urine, but further evaluation of
M. tuberculosis
SOMAmers using other platforms and sample types is warranted.
Redefining Memory: Building the Case for Adaptive NK Cells
Authors: Paust Silke , Blish Catherine A. , Reeves R. Keith 
Published: August 2017

ABSTRACTClassically, natural killer (NK) cells have been defined by nonspecific innate killing of virus-infected and tumor cells. However, burgeoning evidence suggests that the functional repertoire of NK cells is far more diverse than has been previously appreciated, thus raising the possibility that there may be unexpected functional specialization and even adaptive capabilities among NK cell subpopulations. Some of the first evidence that NK cells respond in an antigen-specific fashion came from experiments revealing that subpopulations of murine NK cells were able to respond to a specific murine cytomegalovirus (MCMV) protein and that in the absence of T and B cells, murine NK cells also mediated adaptive immune responses to a secondary challenge with specific haptens. These data have been followed by demonstrations of NK cell memory of viruses and viral antigens in mice and primates. Herein, we discuss different forms of NK cell antigen specificity and how these responses may be tuned to specific viral pathogens, and we provide assessment of the current literature that may explain molecular mechanisms of the novel phenomenon of NK cell memory.
An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1
Authors: Skinner Camille M. , Ivanov Nikita S. , Barr Sarah A. , Chen Yan , Skalsky Rebecca L. 
Published: August 2017

ABSTRACT
Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3′ untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3′-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis.

IMPORTANCE
IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell.
Nidovirus-Associated Proliferative Pneumonia in the Green Tree Python (Morelia viridis)
Authors: Dervas Eva , Hepojoki Jussi , Laimbacher Andrea , Romero-Palomo Fernando , Jelinek Christine , Keller Saskia , Smura Teemu , Hepojoki Satu , Kipar Anja , Hetzel Udo 
Published: August 2017

ABSTRACT

In 2014 we observed a noticeable increase in the number of sudden deaths among green tree pythons (
Morelia viridis
). Pathological examination revealed the accumulation of mucoid material within the airways and lungs in association with enlargement of the entire lung. We performed a full necropsy and histological examination on 12 affected green tree pythons from 7 different breeders to characterize the pathogenesis of this mucinous pneumonia. By histology we could show a marked hyperplasia of the airway epithelium and of faveolar type II pneumocytes. Since routine microbiological tests failed to identify a causative agent, we studied lung tissue samples from a few diseased snakes by next-generation sequencing (NGS). From the NGS data we could assemble a piece of RNA genome whose sequence was <85% identical to that of nidoviruses previously identified in ball pythons and Indian pythons. We then employed reverse transcription-PCR to demonstrate the presence of the novel nidovirus in all diseased snakes. To attempt virus isolation, we established primary cultures of
Morelia viridis
liver and brain cells, which we inoculated with homogenates of lung tissue from infected individuals. Ultrastructural examination of concentrated cell culture supernatants showed the presence of nidovirus particles, and subsequent NGS analysis yielded the full genome of the novel virus Morelia viridis nidovirus (MVNV). We then generated an antibody against MVNV nucleoprotein, which we used alongside RNA
in situ
hybridization to demonstrate viral antigen and RNA in the affected lungs. This suggests that in natural infection MVNV damages the respiratory tract epithelium, which then results in epithelial hyperplasia, most likely as an exaggerated regenerative attempt in association with increased epithelial turnover.

IMPORTANCE
Novel nidoviruses associated with severe respiratory disease were fairly recently identified in ball pythons and Indian pythons. Herein we report on the isolation and identification of a further nidovirus from green tree pythons (
Morelia viridis
) with fatal pneumonia. We thoroughly characterized the pathological changes in the infected individuals and show that nidovirus infection is associated with marked epithelial proliferation in the respiratory tract. We speculate that this and the associated excess mucus production can lead to the animals' death by inhibiting normal gas exchange in the lungs. The virus was predominantly detected in the respiratory tract, which renders transmission via the respiratory route likely. Nidoviruses cause sudden outbreaks with high rates of mortality in breeding collections, and most affected snakes die without prior clinical signs. These findings, together with those of other groups, indicate that nidoviruses are a likely cause of severe pneumonia in pythons.
HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques
Authors: Han Qifeng , Williams Wilton B. , Saunders Kevin O. , Seaton Kelly E. , Wiehe Kevin J. , Vandergrift Nathan , Von Holle Tarra A. , Trama Ashley M. , Parks Robert J. , Luo Kan , Gurley Thaddeus C. , Kepler Thomas B. , Marshall Dawn J. , Montefiori David C. , Sutherland Laura L. , Alam Munir S. , Whitesides John F. , Bowman Cindy M. , Permar Sallie R. , Graham Barney S. , Mascola John R. , Seed Patrick C. , Van Rompay Koen K. A. , Tomaras Georgia D. , Moody M. Anthony , Haynes Barton F. 
Published: August 2017

ABSTRACT
Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.

IMPORTANCE
Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in memory B cells of both adult and neonatal RMs indicated that early vaccination could not overcome gp41 dominant responses.