bluuebunny/crossref_metadata_2025_split huggingface dataset:
Base Salaries, Bonus Payments, and Work Absence among Managers in a German Company
Authors: Pfeifer Christian 
Published: July 2014

AbstractThis paper provides scarce insider econometric evidence on the structure of management compensation and on the incentive effects of fixed base salaries and bonus payments. Six years of personnel data of 177 managers in a German company are analyzed with special emphasis on the highest achievable bonuses under a Management‐by‐Objectives (MBO) incentive scheme. The main finding of panel negative binomial regressions is that higher achievable bonus payments are correlated with fewer absent working days, which supports the incentive effect of performance pay for managers. The fixed base salary component is, however, not significantly correlated with managers’ work absence.
Dynamic, high precision targeting of growth modulating agents is able to trigger pollen tube growth reorientation
Authors: Sanati Nezhad Amir , Packirisamy Muthukumaran , Geitmann Anja 
Published: July 2014

SummaryThe pollen tube is the most rapidly growing cell in the plant kingdom and has the function to deliver the sperm cells for fertilization. The growing tip region of the cell behaves in a chemotropic manner to respond to the guidance cues emitted by the pistil and the female gametophyte, but how it perceives and responds to these directional triggers is virtually unknown. Quantitative assessment of chemotropic behavior can greatly be enhanced by the administration of pharmacological or other biologically active agents at subcellular precision, which is a technical challenge when the target area moves as it grows. We developed a laminar flow based microfluidic device that allows for continuous administration of two different solutions with a movable interface that permits the dynamic targeting of the growing pollen tube apex over prolonged periods of time. Asymmetric administration of calcium revealed that rather than following the highest calcium concentration as would be expected with simple chemotropic behavior, the pollen tube of Camellia targets an optimal concentration suggesting the presence of two superimposed mechanisms. Subcellular application of pectin methyl esterase (PME), an enzyme that modifies the growth behavior by rigidifying the pollen tube cell wall, caused the tube to turn away from the agent – providing important evidence for a previously proposed conceptual model of the growth mechanism.
RCN1/OsABCG5, an ATP‐binding cassette (ABC) transporter, is required for hypodermal suberization of roots in rice (Oryza sativa)
Authors: Shiono Katsuhiro , Ando Miho , Nishiuchi Shunsaku , Takahashi Hirokazu , Watanabe Kohtaro , Nakamura Motoaki , Matsuo Yuichi , Yasuno Naoko , Yamanouchi Utako , Fujimoto Masaru , Takanashi Hideki , Ranathunge Kosala , Franke Rochus B. , Shitan Nobukazu , Nishizawa Naoko K. , Takamure Itsuro , Yano Masahiro , Tsutsumi Nobuhiro , Schreiber Lukas , Yazaki Kazufumi , Nakazono Mikio , Kato Kiyoaki 
Published: July 2014

SummarySuberin is a complex polymer composed of aliphatic and phenolic compounds. It is a constituent of apoplastic plant interfaces. In many plant species, including rice (Oryza sativa), the hypodermis in the outer part of roots forms a suberized cell wall (the Casparian strip and/or suberin lamellae), which inhibits the flow of water and ions and protects against pathogens. To date, there is no genetic evidence that suberin forms an apoplastic transport barrier in the hypodermis. We discovered that a rice reduced culm number1 (rcn1) mutant could not develop roots longer than 100 mm in waterlogged soil. The mutated gene encoded an ATP‐binding cassette (ABC) transporter named RCN1/OsABCG5. RCN1/OsABCG5 gene expression in the wild type was increased in most hypodermal and some endodermal roots cells under stagnant deoxygenated conditions. A GFP‐RCN1/OsABCG5 fusion protein localized at the plasma membrane of the wild type. Under stagnant deoxygenated conditions, well suberized hypodermis developed in wild types but not in rcn1 mutants. Under stagnant deoxygenated conditions, apoplastic tracers (periodic acid and berberine) were blocked at the hypodermis in the wild type but not in rcn1, indicating that the apoplastic barrier in the mutant was impaired. The amount of the major aliphatic suberin monomers originating from C28 and C30 fatty acids or ω‐OH fatty acids was much lower in rcn1 than in the wild type. These findings suggest that RCN1/OsABCG5 has a role in the suberization of the hypodermis of rice roots, which contributes to formation of the apoplastic barrier.
Measurement of salivary adiponectin concentrations in dogs
Authors: Tvarijonaviciute Asta , Carrillo‐Sanchez Juana D. , García‐Martinez Juan D. , Tecles Fernando , Martinez‐Subiela Silvia , German Alexander J. , Ceron Jose J. 
Published: July 2014

BackgroundMeasurement of salivary adiponectin could improve understanding of this adipokine's physiology, and its role in various clinical conditions.ObjectivesThe purpose of the study was to evaluate the utility of a human adiponectin ELISA kit for measurement of salivary adiponectin in dogs, to compare serum and salivary adiponectin concentrations in a healthy dog population, and to evaluate possible effects of tooth‐cleaning on serum and salivary adiponectin concentrations in dogs.MethodsFor analytical validation, precision, accuracy, and lower limit of quantification of the assay were determined with saliva samples. In addition, adiponectin concentrations were quantified in serum and saliva samples from 24 healthy dogs, and from 7 dogs with mild gingivitis before and after a tooth‐cleaning procedure.ResultsThe validation assays for salivary adiponectin had all coefficients of variation <15%, and recovery ranged from 85% to 120%. In the linearity test, interference was observed when measuring adiponectin in saliva, but this was solved by diluting samples 1:4. In healthy dogs, salivary and serum adiponectin concentrations were positively correlated (r = .650; P = .009). After the tooth‐cleaning procedure, salivary adiponectin concentration increased on day 0 (P = .004), but by day 14, concentrations were less than prior to the procedure (P = .041).ConclusionsThe human adiponectin ELISA kit can be used for precise and accurate salivary adiponectin measurement in dogs. Salivary adiponectin increased 24 hours after tooth‐cleaning, possibly due to acute inflammation or adiponectin leakage from the blood after gingival trauma.
Validation of an Enzyme-Linked Immunosorbent Assay That Detects Histoplasma capsulatum Antigenuria in Colombian Patients with AIDS for Diagnosis and Follow-Up during Therapy
Authors: Caceres Diego H. , Scheel Christina M. , Tobón Ángela M. , Ahlquist Cleveland Angela , Restrepo Ángela , Brandt Mary E. , Chiller Tom , Gómez Beatriz L. 
Published: July 2014

ABSTRACTWe validated an antigen capture enzyme-linked immunosorbent assay (ELISA) in Colombian persons with AIDS and proven histoplasmosis and evaluated the correlation between antigenuria and clinical improvement during follow-up. The sensitivity of theHistoplasma capsulatumELISA was 86%, and the overall specificity was 94%. The antigen test successfully monitored the response to therapy.
Autographa californica Multiple Nucleopolyhedrovirus DNA Polymerase C Terminus Is Required for Nuclear Localization and Viral DNA Replication
Authors: Feng Guozhong , Krell Peter J. 
Published: July 2014

ABSTRACT

The DNA polymerase (DNApol) of the baculovirus
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) is essential for viral DNA replication. The DNApol exonuclease and polymerase domains are highly conserved and are considered functional in DNA replication. However, the role of the DNApol C terminus has not yet been characterized. To identify whether only the exonuclease and polymerase domains are sufficient for viral DNA replication, several DNApol C-terminal truncations were cloned into a
dnapol
-null AcMNPV bacmid with a green fluorescent protein (GFP) reporter. Surprisingly, most of the truncation constructs, despite containing both exonuclease and polymerase domains, could not rescue viral DNA replication and viral production in bacmid-transfected Sf21 cells. Moreover, GFP fusions of these same truncations failed to localize to the nucleus. Truncation of the C-terminal amino acids 950 to 984 showed nuclear localization but allowed for only limited and delayed viral spread. The C terminus contains a typical bipartite nuclear localization signal (NLS) motif at residues 804 to 827 and a monopartite NLS motif at residues 939 to 948. Each NLS, as a GFP fusion peptide, localized to the nucleus, but both NLSs were required for nuclear localization of DNApol. Alanine substitutions in a highly conserved baculovirus DNApol sequence at AcMNPV DNApol amino acids 972 to 981 demonstrated its importance for virus production and DNA replication. Collectively, the data indicated that the C terminus of AcMNPV DNApol contains two NLSs and a conserved motif, all of which are required for nuclear localization of DNApol, viral DNA synthesis, and virus production.

IMPORTANCE
The baculovirus DNA polymerase (DNApol) is a highly specific polymerase that allows viral DNA synthesis and hence virus replication in infected insect cells. We demonstrated that the exonuclease and polymerase domains of
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) alone are insufficient for viral DNA synthesis and virus replication. Rather, we identified three features, including two nuclear localization signals and a highly conserved 10-amino-acid sequence in the AcMNPV DNApol C terminus, all three of which are important for both nuclear localization of DNApol and for DNApol activity, as measured by viral DNA synthesis and virus replication.
Diverse Specificities, Phenotypes, and Antiviral Activities of Cytomegalovirus-Specific CD8+T Cells
Authors: Jackson S. E. , Mason G. M. , Okecha G. , Sissons J. G. P. , Wills M. R. 
Published: July 2014

ABSTRACTCD8+T cells specific for pp65, IE1, and IE2 are present at high frequencies in human cytomegalovirus (HCMV)-seropositive individuals, and these have been shown to have phenotypes associated with terminal differentiation, as well as both cytokine and proliferative dysfunctions, especially in the elderly. However, more recently, T cell responses to many other HCMV proteins have been described, but little is known about their phenotypes and functions. Consequently, in this study, we chose to determine the diversity of HCMV-specific CD8+T cell responses to the products of 11 HCMV open reading frames (ORFs) in a cohort of donors aged 20 to 80 years old as well as the ability of the T cells to secrete gamma interferon (IFN-γ). Finally, we also tested their functional antiviral capacity using a novel viral dissemination assay. We identified substantial CD8+T cell responses by IFN-γ enzyme-linked immunospot (ELISPOT) assays to all 11 of these HCMV proteins, and across the cohort, individuals displayed a range of responses, from tightly focused to highly diverse, which were stable over time. CD8+T cell responses to the HCMV ORFs were highly differentiated and predominantly CD45RA+, CD57+, and CD28−, across the cohort. These highly differentiated cells had the ability to inhibit viral spread even following directex vivoisolation. Taken together, our data argue that HCMV-specific CD8+T cells have effective antiviral activity irrespective of the viral protein recognized across the whole cohort and despite viral immune evasion.IMPORTANCEHuman cytomegalovirus (HCMV) is normally carried without clinical symptoms and is widely prevalent in the population; however, it often causes severe clinical disease in individuals with compromised immune responses. HCMV is never cleared after primary infection but persists in the host for life. In HCMV carriers, the immune response to HCMV includes large numbers of virus-specific immune cells, and the virus has evolved many mechanisms to evade the immune response. While this immune response seems to protect healthy people from subsequent disease, the virus is never eliminated. It has been suggested that this continuous surveillance by the immune system may have deleterious effects in later life. The study presented in this paper examined immune responses from a cohort of donors and shows that these immune cells are effective at controlling the virus and can overcome the virus' lytic cycle immune evasion mechanisms.
A Mutation in the DNA Polymerase Accessory Factor of Herpes Simplex Virus 1 Restores Viral DNA Replication in the Presence of Raltegravir
Authors: Zhou Bin , Yang Kui , Wills Elizabeth , Tang Liang , Baines Joel D. 
Published: July 2014

ABSTRACT

Previous reports showed that raltegravir, a recently approved antiviral compound that targets HIV integrase, can inhibit the nuclease function of human cytomegalovirus (HCMV terminase)
in vitro
. In this study, subtoxic levels of raltegravir were shown to inhibit the replication of four different herpesviruses, herpes simplex virus 1 (HSV-1), HSV-2, HCMV, and mouse cytomegalovirus, by 30- to 700-fold, depending on the dose and the virus tested. Southern blotting and quantitative PCR revealed that raltegravir inhibits DNA replication of HSV-1 rather than cleavage of viral DNA. A raltegravir-resistant HSV-1 mutant was generated by repeated passage in the presence of 200 μM raltegravir. The genomic sequence of the resistant virus, designated clone 7, contained mutations in 16 open reading frames. Of these, the mutations F198S in unique long region 15 (U
L
15; encoding the large terminase subunit), A374V in U
L
32 (required for DNA cleavage and packaging), V296I in U
L
42 (encoding the DNA polymerase accessory factor), and A224S in U
L
54 (encoding ICP27, an important transcriptional regulator) were introduced independently into the wild-type HSV-1(F) genome, and the recombinant viruses were tested for raltegravir resistance. Viruses bearing both the U
L
15 and U
L
32 mutations inserted within the genome of the U
L
42 mutant were also tested. While the U
L
15, U
L
32, and U
L
54 mutant viruses were fully susceptible to raltegravir, any virus bearing the U
L
42 mutation was as resistant to raltegravir as clone 7. Overall, these results suggest that raltegravir may be a valuable therapeutic agent against herpesviruses and the antiviral activity targets the DNA polymerase accessory factor rather than the nuclease activity of the terminase.

IMPORTANCE
This paper shows that raltegravir, the antiretrovirus drug targeting integrase, is effective against various herpesviruses. Drug resistance mapped to the herpesvirus DNA polymerase accessory factor, which was an unexpected finding.
Age-Dependent Myeloid Dendritic Cell Responses Mediate Resistance to La Crosse Virus-Induced Neurological Disease
Authors: Taylor Katherine G. , Woods Tyson A. , Winkler Clayton W. , Carmody Aaron B. , Peterson Karin E. 
Published: July 2014

ABSTRACT
La Crosse virus (LACV) is the major cause of pediatric viral encephalitis in the United States; however, the mechanisms responsible for age-related susceptibility in the pediatric population are not well understood. Our current studies in a mouse model of LACV infection indicated that differences in myeloid dendritic cell (mDC) responses between weanling and adult mice accounted for susceptibility to LACV-induced neurological disease. We found that type I interferon (IFN) responses were significantly stronger in adult than in weanling mice. Production of these IFNs required both endosomal Toll-like receptors (TLRs) and cytoplasmic RIG-I-like receptors (RLRs). Surprisingly, IFN expression was not dependent on plasmacytoid DCs (pDCs) but rather was dependent on mDCs, which were found in greater number and induced stronger IFN responses in adults than in weanlings. Inhibition of these IFN responses in adults resulted in susceptibility to LACV-induced neurological disease, whereas postinfection treatment with type I IFN provided protection in young mice. These studies provide a definitive mechanism for age-related susceptibility to LACV encephalitis, where mDCs in young mice are insufficiently activated to control peripheral virus replication, thereby allowing virus to persist and eventually cause central nervous system (CNS) disease.

IMPORTANCE
La Crosse virus (LACV) is the primary cause of pediatric viral encephalitis in the United States. Although the virus infects both adults and children, over 80% of the reported neurological disease cases are in children. To understand why LACV causes neurological disease primarily in young animals, we used a mouse model where weanling mice, but not adult mice, develop neurological disease following virus infection. We found that an early immune response cell type, myeloid dendritic cells, was critical for protection in adult animals and that these cells were reduced in young animals. Activation of these cells during virus infection or after treatment with type I interferon in young animals provided protection from LACV. Thus, this study demonstrates a reason for susceptibility to LACV infection in young animals and shows that early therapeutic treatment in young animals can prevent neurological disease.
New Small-Molecule Inhibitors Effectively Blocking Picornavirus Replication
Authors: Ford Siltz Lauren A. , Viktorova Ekaterina G. , Zhang Ben , Kouiavskaia Diana , Dragunsky Eugenia , Chumakov Konstantin , Isaacs Lyle , Belov George A. 
Published: July 2014

ABSTRACT

Few drugs targeting picornaviruses are available, making the discovery of antivirals a high priority. Here, we identified and characterized three compounds from a library of kinase inhibitors that block replication of poliovirus, coxsackievirus B3, and encephalomyocarditis virus. Using an
in vitro
translation-replication system, we showed that these drugs inhibit different stages of the poliovirus life cycle. A4(1) inhibited both the formation and functioning of the replication complexes, while E5(1) and E7(2) were most effective during the formation but not the functioning step. Neither of the compounds significantly inhibited VPg uridylylation. Poliovirus resistant to E7(2) had a G5318A mutation in the 3A protein. This mutation was previously found to confer resistance to enviroxime-like compounds, which target a phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ)-dependent step in viral replication. Analysis of host protein recruitment showed that E7(2) reduced the amount of GBF1 on the replication complexes; however, the level of PI4KIIIβ remained intact. E7(2) as well as another enviroxime-like compound, GW5074, interfered with viral polyprotein processing affecting both 3C- and 2A-dependent cleavages, and the resistant G5318A mutation partially rescued this defect. Moreover, E7(2) induced abnormal recruitment to membranes of the viral proteins; thus, enviroxime-like compounds likely severely compromise the interaction of the viral polyprotein with membranes. A4(1) demonstrated partial protection from paralysis in a murine model of poliomyelitis. Multiple attempts to isolate resistant mutants in the presence of A4(1) or E5(1) were unsuccessful, showing that effective broad-spectrum antivirals could be developed on the basis of these compounds.

IMPORTANCE
Diverse picornaviruses can trigger multiple human maladies, yet currently, only hepatitis A virus and poliovirus can be controlled with vaccination. The development of antipicornavirus therapeutics is also facing significant difficulties because these viruses readily generate resistance to compounds targeting either viral or cellular factors. Here, we describe three novel compounds that effectively block replication of distantly related picornaviruses with minimal toxicity to cells. The compounds prevent viral RNA replication after the synthesis of the uridylylated VPg primer. Importantly, two of the inhibitors are strongly refractory to the emergence of resistant mutants, making them promising candidates for further broad-spectrum therapeutic development. Evaluation of one of the compounds in an
in vivo
model of poliomyelitis demonstrated partial protection from the onset of paralysis.
TRIM13 Is a Negative Regulator of MDA5-Mediated Type I Interferon Production
Authors: Narayan Kavitha , Waggoner Lisa , Pham Serena T. , Hendricks Gabriel L. , Waggoner Stephen N. , Conlon Joseph , Wang Jennifer P. , Fitzgerald Katherine A. , Kang Joonsoo 
Published: July 2014

ABSTRACT

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are essential intracellular detectors of viral RNA. They contribute to the type I interferon (IFN) response that is crucial for host defense against viral infections. Given the potent antiviral and proinflammatory activities elicited by the type I IFNs, induction of the type I IFN response is tightly regulated. Members of the tripartite motif (TRIM) family of proteins have recently emerged as key regulators of antiviral immunity. We show that TRIM13, an E3 ubiquitin ligase, is expressed in immune cells and is upregulated in bone marrow-derived macrophages upon stimulation with inducers of type I IFN. TRIM13 interacts with MDA5 and negatively regulates MDA5-mediated type I IFN production
in vitro
, acting upstream of IFN regulatory factor 3. We generated
Trim13
−/−
mice and show that upon lethal challenge with encephalomyocarditis virus (EMCV), which is sensed by MDA5,
Trim13
−/−
mice produce increased amounts of type I IFNs and survive longer than wild-type mice.
Trim13
−/−
murine embryonic fibroblasts (MEFs) challenged with EMCV or poly(I·C) also show a significant increase in beta IFN (IFN-β) levels, but, in contrast, IFN-β responses to the RIG-I-detected Sendai virus were diminished, suggesting that TRIM13 may play a role in positively regulating RIG-I function. Together, these results demonstrate that TRIM13 regulates the type I IFN response through inhibition of MDA5 activity and that it functions nonredundantly to modulate MDA5 during EMCV infection.

IMPORTANCE
The type I interferon (IFN) response is crucial for host defense against viral infections, and proper regulation of this pathway contributes to maintaining immune homeostasis. Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are intracellular detectors of viral RNA that induce the type I IFN response. In this study, we show that expression of the gene tripartite motif 13 (
Trim13
) is upregulated in response to inducers of type I IFN and that TRIM13 interacts with both MDA5 and RIG-I
in vitro
. Through the use of multiple
in vitro
and
in vivo
model systems, we show that TRIM13 is a negative regulator of MDA5-mediated type I IFN production and may also impact RIG-I-mediated type I IFN production by enhancing RIG-I activity. This places TRIM13 at a key junction within the viral response pathway and identifies it as one of the few known modulators of MDA5 activity.