bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Genome Sequence of a Novel Duck Hepatitis A Virus Discovered in Southern China
Authors: Wei Chun-ya , Su Shuo , Huang Zhen , Zhu Wan-jun , Chen Ji-dang , Zhao Fu-rong , Wang Yan-jing , Xie Jie-xiong , Wang Heng , Zhang Guihong 
Published: August 2012

ABSTRACT

We report here the complete genomic sequence of a novel duck hepatitis A virus (DHAV) isolated from mixed infections with DHAV type 1 (DHAV-1) and DHAV-3 in ducklings in Southern China. The whole nucleotide sequence had the highest homology with the sequence of DHAV-3 (GenBank accession number
DQ812093
) (96.2%). To our knowledge, this is the first report of gene rearrangement between DHAV-1 and DHAV-3, and it will help to understand the epidemiology and molecular characteristics of duck hepatitis A virus in Southern China.
Murine Gammaherpesvirus 68 LANA Acts on Terminal Repeat DNA To Mediate Episome Persistence
Authors: Habison Aline C. , Beauchemin Chantal , Simas J. Pedro , Usherwood Edward J. , Kaye Kenneth M. 
Published: August 2012

ABSTRACTMurine gammaherpesvirus 68 (MHV68) ORF73 (mLANA) has sequence homology to Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA). LANA acts on the KSHV terminal repeat (TR) elements to mediate KSHV episome maintenance. Disruption of mLANA expression severely reduces the ability of MHV68 to establish latent infection in mice, consistent with the possibility that mLANA mediates episome persistence. Here we assess the roles of mLANA and MHV68 TR (mTR) elements in episome persistence. mTR-associated DNA persisted as an episome in latently MHV68-infected tumor cells, demonstrating that the mTR elements can serve as acis-acting element for MHV68 episome maintenance. In some cases, both control vector and mTR-associated DNAs integrated into MHV68 episomal genomes. Therefore, we also assessed the roles of mTRs as well as mLANA in the absence of infection. DNA containing both mLANA and mTRs incispersisted as an episome in murine A20 or MEF cells. In contrast, mTR DNA never persisted as an episome in the absence of mLANA. mLANA levels were increased when mLANA was expressed from its native promoters, and episome maintenance was more efficient with higher mLANA levels. Increased numbers of mTRs conferred more efficient episome maintenance, since DNA containing mLANA and eight mTR elements persisted more efficiently in A20 cells than did DNA with mLANA and two or four mTRs. Similar to KSHV LANA, mLANA broadly associated with mitotic chromosomes but relocalized to concentrated dots in the presence of episomes. Therefore, mLANA acts on mTR elements to mediate MHV68 episome persistence.
Evidence for pH-Dependent Protease Activity in the Adeno-Associated Virus Capsid
Authors: Salganik Maxim , Venkatakrishnan Balasubramanian , Bennett Antonette , Lins Bridget , Yarbrough Joseph , Muzyczka Nicholas , Agbandje-McKenna Mavis , McKenna Robert 
Published: August 2012

ABSTRACT

Incubation of highly purified adeno-associated virus (AAV) capsids
in vitro
at pH 5.5 induced significant autocleavage of capsid proteins at several amino acid positions. No autocleavage was seen at pH 7.5. Examination of other AAV serotypes showed at least two different pH-induced cleavage patterns, suggesting that different serotypes have evolved alternative protease cleavage sites. In contrast, incubation of AAV serotypes with an external protease substrate showed that purified AAV capsid preparations have robust protease activity at neutral pH but not at pH 5.5, opposite to what is seen with capsid protein autocleavage. Several lines of evidence suggested that protease activity is inherent in AAV capsids and is not due to contaminating proteins. Control virus preparations showed no protease activity on external substrates, and filtrates of AAV virus preparations also showed no protease activity contaminating the capsids. Further, N-terminal Edman sequencing identified unique autocleavage sites in AAV1 and AAV9, and mutagenesis of amino acids adjacent to these sites eliminated cleavage. Finally, mutation of an amino acid in AAV2 (E563A) that is in a conserved pH-sensitive structural region eliminated protease activity on an external substrate but did not seem to affect autocleavage. Taken together, our data suggested that AAV capsids have one or more protease active sites that are sensitive to pH induction. Further, it appears that acidic pHs comparable to those seen in late endosomes induce a structural change in the capsid that induces autolytic protease activity. The pH-dependent protease activity may have a role in viral infection.
Regulated Interaction of Tegument Proteins UL16 and UL11 from Herpes Simplex Virus
Authors: Chadha Pooja , Han Jun , Starkey Jason L. , Wills John W. 
Published: August 2012

ABSTRACT

It is well known that proteins in the tegument (located between the viral capsid and envelope proteins) play critical roles in the assembly and budding of herpesviruses. Tegument proteins UL16 and UL11 of herpes simplex virus (HSV) are conserved among all the
Herpesviridae
. Although these proteins directly interact
in vitro
, UL16 was found to colocalize poorly with UL11 in cotransfected cells. To explain this discrepancy, we hypothesized that UL16 is initially made in an inactive form and is artificially transformed to the binding-competent state when cells are disrupted. Consistent with a regulated interaction, UL16 was able to fully colocalize with UL11 when a large C-terminal segment of UL16 was removed, creating mutant UL16(1-155). Moreover, membrane flotation assays revealed a massive movement of this mutant to the top of sucrose gradients in the presence of UL11, whereas both the full-length UL16 and the C-terminal fragment (residues 156 to 373) remained at the bottom. Further evidence for the presence of a C-terminal regulatory domain was provided by single-amino-acid substitutions at conserved cysteines (C269S, C271S, and C357S), which enabled the efficient interaction of full-length UL16 with UL11. Lastly, the binding site for UL11 was further mapped to residues 81 to 155, and to our surprise, the 5 Cys residues within UL16(1-155) are not required, even though the modification of free cysteines in UL16 with
N
-ethylmaleimide does in fact prevent binding. Collectively, these results reveal a regulatory function within the C-terminal region of UL16 that controls an N-terminal UL11-binding activity.
In Vivo
-Validated Essential Genes Identified in Acinetobacter baumannii by Using Human Ascites Overlap Poorly with Essential Genes Detected on Laboratory Media
Authors: Umland Timothy C. , Schultz L. Wayne , MacDonald Ulrike , Beanan Janet M. , Olson Ruth , Russo Thomas A. 
Published: August 2012

ABSTRACT

A critical feature of a potential antimicrobial target is the characteristic of being essential for growth and survival during host infection. For bacteria, genome-wide essentiality screens are usually performed on rich laboratory media. This study addressed whether genes detected in that manner were optimal for the identification of antimicrobial targets since the
in vivo
milieu is fundamentally different. Mutant derivatives of a clinical isolate of
Acinetobacter baumannii
were screened for growth on human ascites, an
ex vivo
medium that reflects the infection environment. A subset of 34 mutants with unique gene disruptions that demonstrated little to no growth on ascites underwent evaluation in a rat subcutaneous abscess model, establishing 18 (53%) of these genes as
in vivo
essential. The putative gene products all had annotated biological functions, represented unrecognized or underexploited antimicrobial targets, and could be grouped into five functional categories: metabolic, two-component signaling systems, DNA/RNA synthesis and regulation, protein transport, and structural. These
A. baumannii in vivo
essential genes overlapped poorly with the sets of essential genes from other Gram-negative bacteria catalogued in the Database of Essential Genes (DEG), including those of
Acinetobacter baylyi
, a closely related species. However, this finding was not due to the absence of orthologs. None of the 18
in vivo
essential genes identified in this study, or their putative gene products, were targets of FDA-approved drugs or drugs in the developmental pipeline, indicating that a significant portion of the available target space within pathogenic Gram-negative bacteria is currently neglected.

IMPORTANCE
The human pathogen
Acinetobacter baumannii
is of increasing clinical importance, and a growing proportion of isolates are multiantimicrobial-resistant, pan-antimicrobial-resistant, or extremely resistant strains. This scenario is reflective of the general problem of a critical lack of antimicrobials effective against antimicrobial-resistant Gram-negative bacteria, such as
Pseudomonas aeruginosa
,
Klebsiella pneumoniae
,
Enterobacter
sp., and
Escherichia coli
. This study identified a set of
A. baumannii
genes that are essential for growth and survival during infection and demonstrated the importance of using clinically relevant media and
in vivo
validation while screening for essential genes for the purpose of developing new antimicrobials. Furthermore, it established that if a gene is absent from the Database of Essential Genes, it should not be excluded as a potential antimicrobial target. Lastly, a new set of high-value potential antimicrobial targets for pathogenic Gram-negative bacteria has been identified.
Evidence for Cascades of Perturbation and Adaptation in the Metabolic Genes of Higher Termite Gut Symbionts
Authors: Zhang Xinning , Leadbetter Jared R. 
Published: August 2012

ABSTRACTTermites and their gut microbes engage in fascinating dietary mutualisms. Less is known about how these complex symbioses have evolved after first emerging in an insect ancestor over 120 million years ago. Here we examined a bacterial gene, formate dehydrogenase (fdhF), that is key to the mutualism in 8 species of “higher” termite (members of theTermitidae, the youngest and most biomass-abundant and species-rich termite family). Patterns offdhFdiversity in the gut communities of higher termites contrasted strongly with patterns in less-derived (more-primitive) insect relatives (wood-feeding “lower” termites and roaches). We observed phylogenetic evidence for (i) the sweeping loss of several clades offdhFthat may reflect extinctions of symbiotic protozoa and, importantly, bacteria dependent on them in the last common ancestor of all higher termites and (ii) a radiation of genes from the (possibly) single allele that survived. Sweeping gene loss also resulted in (iii) the elimination of an entire clade of genes encoding selenium (Se)-independent enzymes from higher termite gut communities, perhaps reflecting behavioral or morphological innovations in higher termites that relaxed preexisting environmental limitations of Se, a dietary trace element. Curiously, several higher termite gut communities may have subsequently reencountered Se limitation, reinventing genes for Se-independent proteins via convergent evolution. Lastly, the presence of a novelfdhFlineage within litter-feeding and subterranean higher (but not other) termites may indicate recent gene “invasion” events. These results imply that cascades of perturbation and adaptation by distinct evolutionary mechanisms have impacted the evolution of complex microbial communities in a highly successful lineage of insects.IMPORTANCESince patterns of relatedness between termite hosts are broadly mirrored by the relatedness of their symbiotic gut microbiota, coevolution between hosts and gut symbionts is rightly considered an important force that has shaped dietary mutualism since its inception over 120 million years ago. Apart from that concerning lateral gene or symbiont transfer between termite gut communities (for which no evidence yet exists), there has been little discussion of alternative mechanisms impacting the evolution of mutualism. Here we provide strong gene-based evidence for past environmental perturbations creating significant upheavals that continue to reverberate throughout the gut communities of species comprising a single termite lineage. We suggest that symbiont extinction events, sweeping gene losses, evolutionary radiations, relaxation and reemergence of key nutritional pressures, convergent evolution of similar traits, and recent gene invasions have all shaped gene composition in the symbiotic gut microbial communities of higher termites, currently the most dominant and successful termite family on Earth.
New alternate hosts for the rustsCronartium ribicolaandCronartium flaccidumin Finland
Authors: Kaitera Juha , Hiltunen Ritva 
Published: August 2012

We explored the potential of the North European flora and some garden plants growing naturally outside Europe to support a reservoir of pine stem rusts. Live plants and detached leaves of 35 species in 16 families (Solanaceae, Verbenaceae, Grossulariaceae, Paeoniaceae, Balsaminaceae, Gentianaceae, Scrophulariaceae, Loasaceae, Tropaeolaceae, Acanthaceae, Myricaceae, Phrymaceae, Plantaginaceae, Orobanchaceae, Apocynaceae, and Fagaceae) were inoculated in the greenhouse and (or) laboratory with aeciospores of Cronartium ribicola J.C. Fisch. and Cronartium flaccidum (Alb. & Schwein) G. Winter in 2010. Cronartium flaccidum produced uredinia and (or) telia in 14 species in nine families, 11 of which represent new alternate hosts in Finland and nine also elsewhere (excluding Nemesia versicolor and Tropaeolum majus L.): Euphrasia stricta D. Wof. ex J.F. Lehm., N. versicolor E. Mey. ex Benth., Nemesia strumosa Benth., Verbena × hybrida Voss., Verbena officinalis L., Veronica longifolia L., Impatiens glandulifera Royle, T. majus, Loasa triphylla Juss., Asclepias incarnata L., and Bartsia alpina L. Cronartium ribicola formed fruitbodies in nine species and cultivars in five families, five of which are new alternate hosts for this species in Finland and also elsewhere: Mentzelia lindleyi Torr. & A. Gray, A. incarnata, B. alpina, L. triphylla, and T. majus. Both species of Cronartium infected four alternate hosts, each in its own family. The alternate host range of each Cronartium was wider than expected and wider than that previously described. In local natural forests, Euphrasia , Veronica , and Bartsia (in northern Finland) are potential hosts that are common and may be able to spread these rusts. The recently established ornamental I. glandulifera could provide the means to spread C. flaccidum to Scots pine ( Pinus sylvestris L.) in southern Finland, and species of Mentzelia may be important for the spread of C. ribicola.
Long-term effects of thinning on growth and yield of an upland black spruce stand
Authors: Soucy Michel , Lussier Jean-Martin , Lavoie Luc 
Published: August 2012

Knowledge of the long-term effects of silviculture treatments is crucial to forest management. The long-term effects of thinning, a common and widely used silviculture treatment, is little documented for upland black spruce ( Picea mariana (Mill.) Britton, Sterns & Poggenb.) stands. We revisited a partial cutting experiment installed in 1961 in a 65-year-old unmanaged upland black spruce stand. The aim was to document the long-term effects of thinning on tree and stand growth and to complete previously published results of the first 15 years of response to thinning by determining its influence in terms of merchantable volume. Free thinning was applied following three intensities: 0%, 25%, and 50% of total basal area removal. The retrospective analysis of growth rings showed that the response over the first 15 years was less significant when determined in net merchantable volume instead of net total volume. Heavily thinned plots, nonetheless, showed a net stand merchantable volume increment 33% greater than that of the unthinned plots. In the longer term, a spruce budworm ( Choristoneura fumiferana Clemens) outbreak affected the site; nevertheless, the heavily thinned plots maintained a superior tree growth rate and did not show senescence mortality like the other plots, allowing stand volume to catch up to that of the unthinned plots after 33 years. Results suggested that thinning upland black spruce stands may be useful in mitigating reductions in volume production associated with growing stands to longer rotations as called for by certain ecosystem-based management approaches.
Application of shadow fraction models for estimating attributes of northern boreal forests
Authors: Luther Joan E. , Fournier Richard A. , Houle Mélanie , Leboeuf Antoine , Piercey Douglas E. 
Published: August 2012

A shadow fraction method was developed previously for mapping forest attributes of northern black spruce ( Picea mariana (Mill.) Britton, Sterns & Poggenb.) forests. This paper evaluates application of the method for (i) balsam fir stands ( Abies balsamea (L.) Mill.), (ii) stands with higher volume and biomass than those of previous studies, and (iii) stands with a higher composition of deciduous trees and steeper slopes. Models developed for new test sites in (i) central Labrador and (ii) western Newfoundland were not statistically different from previous models for biomass, volume, and basal area. Relative root mean square errors (RMSEr) for central Labrador were slightly lower than those found in other test sites (RMSEr: 24%–29%) but higher for western Newfoundland (RMSEr = 37%–43%), attributed to the higher upper limit of measured attributes and increased presence of deciduous trees. Results suggest that reasonable estimates can be generated for conifer forests of northeastern Canada; however, an alternative solution is needed where mixed and deciduous stands are prevalent. Measurement of ground plots over a wider range of species composition and forest structure is recommended for broader application to northern boreal forests and to further assess the potential role of the shadow fraction method in national-scale inventory programs.
Reconstructing the competitive dynamics of mixed-oak neighborhoods
Authors: Zenner Eric K. , Heggenstaller Daniel J. , Brose Patrick H. , Peck JeriLynn E. , Steiner Kim C. 
Published: August 2012

The disparity between the potential for latent oak dominance within a stand and their region-wide decline in importance value raises questions about the competitiveness of oaks in early stand dynamics. We reconstructed tree height growth dynamics in mixed-species neighborhoods to determine if currently dominant oaks were ever shorter than their competitors and at what age currently subordinate oaks fell behind. In 23–36 year old mixed-oak stands in two physiographic provinces of Pennsylvania, we identified dominant and subordinate northern red oaks ( Quercus rubra L.) and chestnut oaks ( Quercus prinus L.) competing with adjacent non-oaks (red maple ( Acer rubrum L.), sweet birch ( Betula lenta L.), and black cherry ( Prunus serotina Ehrh.)) of equal crown class. In each stand, we randomly selected 20 tree neighborhoods and collected stem cross sections every metre from the base to the tip of each tree. In the Allegheny Plateau province, dominant northern red oaks never averaged more than 2 m shorter than their competitors, while by age 20, subordinate oaks were commonly more than 2 m behind. Dominant chestnut oaks in the Ridge and Valley province were never more than 1 m shorter than their competitors; subordinate oaks, however, were generally always at least a metre behind. In both regions, growth dynamics of currently subordinate trees were indistinguishable from those of currently dominant trees during their first decade. Because oaks that were considerably behind at age 15 were likely to be subordinate by age 30, the window of opportunity for release to prevent oaks from becoming permanently overtopped and unable to recover may thus be relatively early (age 10–20).
Tumor Cell Autophagy as an Adaptive Response Mediating Resistance to Treatments Such as Antiangiogenic Therapy
Authors: Hu Yu-Long , Jahangiri Arman , DeLay Michael , Aghi Manish K. 
Published: August 2012

AbstractAutophagy is a lysosomal degradation pathway that can sequester cytosolic material, including organelles, nonspecifically in a process called nonselective macroautophagy, or target specific protein aggregates designated for destruction in a process called selective autophagy. Autophagy is one mechanism that enables tumor cells to survive stressors in the tumor microenvironment, as well as injuries caused by treatments such as chemotherapy and radiation therapy. The complexity of the role of autophagy in cancer is underscored by evidence that autophagy can allow premalignant cells to escape the genotoxic stress and inflammation that promote tumorigenesis, and that some tumor cells exhibit loss of autophagy capacity altogether through molecular mechanisms that have not yet been defined. Efforts to understand and modulate the autophagy pathway will be crucial to maximize the full therapeutic potential of cancer therapies that are currently hindered by tumor cell autophagy as a resistance mechanism. Cancer Res; 72(17); 4294–9. ©2012 AACR.
TNF-α Mediates Macrophage-Induced Bystander Effects through Netrin-1
Authors: Yang Yonghong , Wang Xingmin , Moore Danny R. , Lightfoot Stanley A. , Huycke Mark M. 
Published: August 2012

Abstract
Macrophage-induced bystander effects have been implicated as an important mediator of chromosomal instability and colon cancer triggered by Enterococcus faecalis, a human intestinal commensal bacteria. There is little understanding about how inflammatory cytokines mediate bystander effects, but questions in this area are important because of the pivotal contributions made by inflammatory processes to cancer initiation and progression. Here, we report that the central proinflammatory cytokine TNF-α acts as a diffusible mediator of the bystander effects induced by macrophages, an effect caused by a proliferation of macrophages that trigger epithelial cell production of Netrin-1, a neuronal guidance molecule. TNF-α-mediated bystander assays used a murine coculture system of primary colonic epithelial cells and E. faecalis-infected macrophages (in vitro), with an interleukin 10 (IL-10)-deficient mouse model of colon cancer that involves long-term colonization with E. faecalis (in vivo). In cell cocultures, we observed increased expression of the TNF-α receptor Tnfrsf1b and Netrin-1. These effects were blocked by anti-TNF-α antibody or by pretreatment with an inhibitor of NF-κB signaling. RNAi-mediated attenuation of Tnfrsf1b decreased TNF-α-induced netrin-1 production and augmented epithelial cell apoptosis in culture. Extending these observations, colon biopsies from E. faecalis-colonized IL-10−/− mice exhibited crypt hyperplasia and increased staining for macrophages, TNF-α, netrin-1, NF-κB, Tnfrsf1b, and the proliferation marker proliferating cell nuclear antigen while also displaying a reduction in epithelial cell apoptosis. Together, our results define a pathway for macrophage-induced bystander effects in which TNF-α triggers TNFRSF1b receptor signaling leading to increased production of Netrin-1, crypt hyperplasia, and decreased epithelial cell apoptosis. In elucidating an important commensal-associated proinflammatory mechanism in the intestinal microenvironment, our work highlights the role of Netrin-1 and a specific TNF-α receptor as candidate targets to prevent or treat colorectal cancer. Cancer Res; 72(20); 5219–29. ©2012 AACR.