bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open‐Mindedness as Engagement
Authors: Kwong Jack M. C. 
Published: March 2016

AbstractOpen‐mindedness is an under‐explored topic in virtue epistemology, despite its assumed importance for the field. Questions about it abound and need to be answered. For example, what sort of intellectual activities are central to it? Can one be open‐minded about one's firmly held beliefs? Why should we strive to be open‐minded? This paper aims to shed light on these and other pertinent issues. In particular, it proposes a view that construes open‐mindedness as engagement, that is, a willingness to entertain novel ideas in one's cognitive space and to accord them serious consideration.
Lockean Empathy
Authors: Marshall Colin 
Published: March 2016

AbstractThis paper offers an epistemic defense of empathy, drawing on John Locke's theory of ideas. Locke held that ideas of shape, unlike ideas of color, had a distinctive value: resembling qualities in their objects. I argue that the same is true of empathy, as when someone is pained by someone's pain. This means that empathy has the same epistemic value or objectivity that Locke and other early modern philosophers assigned to veridical perceptions of shape. For this to hold, pain and pleasure must be a primary quality of the mind, just as shape is a primary quality of bodies. Though Locke did not make that claim, I argue that pain and pleasure satisfy his criteria for primary qualities. I consider several objections to the analogy between empathy and shape‐perception and show how Locke's theory has resources for answering them. In addition, the claim that empathetic ideas are object‐matching sidesteps Berkeley's influential objection to Locke's theory of resemblance. I conclude by briefly considering the prospects for a similar defense of empathy in contemporary terms.
The role of PLDα1 in providing specificity to signal‐response coupling by heterotrimeric G‐protein components in Arabidopsis
Authors: Roy Choudhury Swarup , Pandey Sona 
Published: March 2016

SummaryHeterotrimeric G‐proteins comprised of Gα, Gβ and Gγ subunits are important signal transducers in all eukaryotes. In plants, G‐proteins affect multiple biotic and abiotic stress responses, as well as many developmental processes, even though their repertoire is significantly limited compared with that in metazoan systems. One canonical and three extra‐large Gα, 1 Gβ and 3 Gγ proteins represent the heterotrimeric G‐protein complex in Arabidopsis, and a single regulatory protein, RGS1, is one of the few known biochemical regulators of this signaling complex. This quantitative disparity between the number of signaling components and the range of processes they influence is rather intriguing. We now present evidence that the phospholipase Dα1 protein is a key component and modulator of the G‐protein complex in affecting a subset of signaling pathways. We also show that the same G‐protein subunits and their modulators exhibit distinct physiological and genetic interactions depending on specific signaling and developmental pathways. Such developmental plasticity and interaction specificity likely compensates for the lack of multiplicity of individual subunits, and helps to fine tune the plants' responses to constantly changing environments.
Sudden acquired retinal degeneration in dogs: breed distribution of 495 canines
Authors: Heller Amanda R. , van der Woerdt Alexandra , Gaarder James E. , Sapienza John S. , Hernandez‐Merino Elena , Abrams Kenneth , Church Melanie L. , La Croix Noelle 
Published: March 2016

AbstractPurposeThe purpose of this study was to describe breed, age, gender, and weight distribution of dogs affected with sudden acquired retinal degeneration (SARD) and to investigate whether SARD is more common in small breed dogs.MethodsMedical records of dogs diagnosed with SARD confirmed by an electroretinogram were reviewed. Breed, age, gender, and weight were recorded when available. The same data were obtained for dogs with SARD described in the veterinary literature.ResultsThree hundred and two dogs were included from the ophthalmology practices and 193 dogs from the veterinary literature. Sixty breeds were present in the study. Mixed‐breed dogs were the most common at 108 dogs (21.8%), followed by the Dachshund (68, 13.7%), Chinese Pug (44, 8.9%), Miniature Schnauzer (39, 7.9%), Maltese (23, 4.6%), Cocker Spaniel (22, 4.4%), Bichon Frise (18, 3.6%), Beagle (16, 3.2%), Brittany (15, 3.0%), and Pomeranian (10, 2.0%). Fifty other breeds were represented by 1–9 dogs each. The median age was 9 years (range = 10 months–16 years). The weight was known for 197 dogs. About 60.9% of dogs were less than 25 pounds, 31.5% were between 25 and 50 pounds, and 7.6% were greater than 50 pounds. Gender was recorded in 393 dogs: 217 female dogs and 176 male dogs.ConclusionsAs previously reported, SARD is most common in middle‐aged to older dogs. Smaller dogs of less than 25 pounds appear overrepresented, while large/giant breed dogs of greater than 50 pounds are infrequently diagnosed. In this study, there was no statistical significance between female and male dogs.
Cryptic speciation in the narrow‐headed vole Lasiopodomys (Stenocranius) gregalis (Rodentia: Cricetidae)
Authors: Petrova Tatyana V. , Tesakov Alexey S. , Kowalskaya Yulia M. , Abramson Natalia I. 
Published: March 2016

Recent study on Lasiopodomys (Stenocranius) gregalis has revealed four clear mitochondrial lineages with differences exceeding the species level. The most divergent is the clade from south‐eastern Transbaikalia. Multilocus (six nuclear genes), morphological (dental characters of m1 and M3) and behavioural (breeding experiments) analyses were conducted to test the hypothesis that L. gregalis is a complex of two cryptic species. All of the applied methods distinguish the independent status of voles from south‐eastern Transbaikalia. This clade occupies a portion of the distribution range of the currently valid subspecies L. g. raddei including its terra typica. According to the results of cyt b analysis, the lectotype of L. g. raddei belongs to the Transbaikal clade. We re‐establish the species status for the taxon Lasiopodomys raddei including populations from south‐eastern Transbaikalia, as a cryptic species of the narrow‐headed vole complex.
Maximal expiratory pressure and Valsalva manoeuvre do not produce similar cardiovascular responses in healthy men
Authors: Minatel Vinicius , Takahashi Anielle C. M. , Perseguini Natália Maria , Milan Juliana Cristina , Castello‐Simões Viviane , Gomes Ellen C. , Borghi‐Silva Audrey , Catai Aparecida Maria 
Published: March 2016

New Findings

What is the central question of this study?
This is the first study to evaluate and describe the cardiovascular responses during maximal expiratory pressure compared with the Valsalva manoeuvre, and whether those responses are similar.

What is the main finding and its importance?
This study showed that the duration of the manoeuvres appears to be responsible for the different physiological mechanisms involved in the cardiovascular responses to each manoeuvre and that the intensity of expiratory effort was related to the response in maximal expiratory pressure. These results are important to identify the risks to which subjects are exposed when performing these manoeuvres.

The main purpose of this study was to compare the cardiovascular responses between the Valsalva manoeuvre (VM) and maximal expiratory pressure (MEP) and to evaluate the effect of age on these responses. Twenty‐eight healthy men were evaluated and divided into two groups, younger (n = 15, 25 ± 5 years) and middle aged (n = 13, 50 ± 5 years), and they performed the VM and MEP measurement. The VM consisted of an expiratory effort (40 mmHg) against a manometer for 15 s, and the MEP was performed according to American Thoracic Society guidelines. The cardiovascular responses were analysed at rest, isotime (3 s), peak, nadir and recovery, and the cardiovascular variations (Δ) were calculated as peak or isotime minus resting values. For the statistical analysis, we used two‐way ANOVA (P < 0.05). We observed that MEP and the VM generate similar changes in cardiac output (P > 0.05), but MEP presents higher values for mean arterial pressure (MAPPeak, MAPIsotime, ΔMAP and ΔMAPIsotime) than those observed in the VM (P < 0.05). The execution time of the manoeuvres (VM ∼15 s and MEP ∼5 s) appears to be largely responsible for the activation of different physiological mechanisms involved in the cardiovascular control for each manoeuvre, and the intensity of expiratory effort is related to the higher response of MAP and peripheral vascular resistance (PVRIsotime and ΔPVRIsotime) during MEP (P < 0.05). Moreover, it appears that age affects only the heart rate and PVR responses (P < 0.05), which were higher in the young and middle‐aged group, respectively. Based on these findings, we can conclude that MEP and the VM do not generate similar cardiovascular responses, except for cardiac output.
Investigation of Linezolid Resistance in Staphylococci and Enterococci
Authors: Doern Christopher D. , Park Jason Y. , Gallegos Michael , Alspaugh Debbie , Burnham Carey-Ann D. 
Published: March 2016

ABSTRACT

The objective of this study was to investigate an apparent increase in linezolid-nonsusceptible staphylococci and enterococci following a laboratory change in antimicrobial susceptibility testing from disk diffusion to an automated susceptibility testing system. Isolates with nonsusceptible results (
n
= 27) from Vitek2 were subjected to a battery of confirmatory testing which included disk diffusion, Microscan broth microdilution, Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution, gradient diffusion (Etest), 23S rRNA gene sequencing, and
cfr
PCR. Our results show that there is poor correlation between methods and that only 70 to 75% of isolates were confirmed as linezolid resistant with alternative phenotypic testing methods (disk diffusion, Microscan broth microdilution, CLSI broth microdilution, and Etest). 23S rRNA gene sequencing identified mutations previously associated with linezolid resistance in 16 (59.3%) isolates, and the
cfr
gene was detected in 3 (11.1%) isolates. Mutations located at positions 2576 and 2534 of the 23S rRNA gene were most common. In addition, two previously undescribed variants (at positions 2083 and 2345 of the 23S rRNA gene) were also identified and may contribute to linezolid resistance.
Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques
Authors: Hensley-McBain Tiffany , Zevin Alexander S. , Manuzak Jennifer , Smith Elise , Gile Jillian , Miller Charlene , Agricola Brian , Katze Michael , Reeves R. Keith , Kraft Colleen S. , Langevin Stanley , Klatt Nichole R. 
Published: March 2016

ABSTRACTAn altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4+T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.IMPORTANCEDue to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4+T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.
Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response
Authors: Conn Kristen L. , Wasson Peter , McFarlane Steven , Tong Lily , Brown James R. , Grant Kyle G. , Domingues Patricia , Boutell Chris 
Published: March 2016

ABSTRACT

S
mall
u
biquitin-like
mo
difier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity.

IMPORTANCE
Posttranslational modifications with
s
mall
u
biquitin-like
mo
difier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The
p
rotein
i
nhibitor of
a
ctivated
S
TAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling. We now identify a unique and contrasting role for PIAS proteins as positive regulators of the intrinsic antiviral immune response to herpes simplex virus 1 (HSV-1) infection. We show that PIAS4 relocalizes to nuclear domains that contain viral DNA throughout infection. Depletion of PIAS4, either alone or in combination with the intrinsic antiviral factor promyelocytic leukemia protein, significantly impairs the intrinsic antiviral immune response to HSV-1 infection. Our data reveal a novel and dynamic role for PIAS4 in the cellular-mediated restriction of herpesviruses and establish a new functional role for the PIAS family of SUMO ligases in the intrinsic antiviral immune response to DNA virus infection.
The RNA Helicase eIF4A Is Required for Sapovirus Translation
Authors: Hosmillo Myra , Sweeney Trevor R. , Chaudhry Yasmin , Leen Eoin , Curry Stephen , Goodfellow Ian , Cho Kyoung-Oh 
Published: March 2016

ABSTRACT
The eukaryotic initiation factor 4A (eIF4A) is a DEAD box helicase that unwinds RNA structure in the 5′ untranslated region (UTR) of mRNAs. Here, we investigated the role of eIF4A in porcine sapovirus VPg-dependent translation. Using inhibitors and dominant-negative mutants, we found that eIF4A is required for viral translation and infectivity, suggesting that despite the presence of a very short 5′ UTR, eIF4A is required to unwind RNA structure in the sapovirus genome to facilitate virus translation.
Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle
Authors: Biedenkopf Nadine , Lier Clemens , Becker Stephan 
Published: March 2016

ABSTRACT
Ebola virus is the causative agent of a severe fever with high fatality rates in humans and nonhuman primates. The regulation of Ebola virus transcription and replication currently is not well understood. An important factor regulating viral transcription is VP30, an Ebola virus-specific transcription factor associated with the viral nucleocapsid. Previous studies revealed that the phosphorylation status of VP30 impacts viral transcription. Together with NP, L, and the polymerase cofactor VP35, nonphosphorylated VP30 supports viral transcription. Upon VP30 phosphorylation, viral transcription ceases. Phosphorylation weakens the interaction between VP30 and the polymerase cofactor VP35 and/or the viral RNA. VP30 thereby is excluded from the viral transcription complex, simultaneously leading to increased viral replication which is supported by NP, L, and VP35 alone. Here, we use an infectious virus-like particle assay and recombinant viruses to show that the dynamic phosphorylation of VP30 is critical for the cotransport of VP30 with nucleocapsids to the sites of viral RNA synthesis, where VP30 is required to initiate primary viral transcription. We further demonstrate that a single serine residue at amino acid position 29 was sufficient to render VP30 active in primary transcription and to generate a recombinant virus with characteristics comparable to those of wild-type virus. In contrast, the rescue of a recombinant virus with a single serine at position 30 in VP30 was unsuccessful. Our results indicate critical roles for phosphorylated and dephosphorylated VP30 during the viral life cycle.

IMPORTANCE
The current Ebola virus outbreak in West Africa has caused more than 28,000 cases and 11,000 fatalities. Very little is known regarding the molecular mechanisms of how the Ebola virus transcribes and replicates its genome. Previous investigations showed that the transcriptional support activity of VP30 is activated upon VP30 dephosphorylation. The current study reveals that the situation is more complex and that primary transcription as well as the rescue of recombinant Ebola virus also requires the transient phosphorylation of VP30. VP30 encodes six N-proximal serine residues that serve as phosphorylation acceptor sites. The present study shows that the dynamic phosphorylation of serine at position 29 alone is sufficient to activate primary viral transcription. Our results indicate a series of phosphorylation/dephosphorylation events that trigger binding to and release from the nucleocapsid and transcription complex to be essential for the full activity of VP30.
Bacterial Vegetative Insecticidal Proteins (Vip) from Entomopathogenic Bacteria
Authors: Chakroun Maissa , Banyuls Núria , Bel Yolanda , Escriche Baltasar , Ferré Juan 
Published: March 2016

SUMMARYEntomopathogenic bacteria produce insecticidal proteins that accumulate in inclusion bodies or parasporal crystals (such as the Cry and Cyt proteins) as well as insecticidal proteins that are secreted into the culture medium. Among the latter are the Vip proteins, which are divided into four families according to their amino acid identity. The Vip1 and Vip2 proteins act as binary toxins and are toxic to some members of the Coleoptera and Hemiptera. The Vip1 component is thought to bind to receptors in the membrane of the insect midgut, and the Vip2 component enters the cell, where it displays its ADP-ribosyltransferase activity against actin, preventing microfilament formation. Vip3 has no sequence similarity to Vip1 or Vip2 and is toxic to a wide variety of members of the Lepidoptera. Its mode of action has been shown to resemble that of the Cry proteins in terms of proteolytic activation, binding to the midgut epithelial membrane, and pore formation, although Vip3A proteins do not share binding sites with Cry proteins. The latter property makes them good candidates to be combined with Cry proteins in transgenic plants (Bacillus thuringiensis-treated crops [Bt crops]) to prevent or delay insect resistance and to broaden the insecticidal spectrum. There are commercially grown varieties of Bt cotton and Bt maize that express the Vip3Aa protein in combination with Cry proteins. For the most recently reported Vip4 family, no target insects have been found yet.
Lessons Learned from
In Vivo
Studies of a Viral Noncoding RNA
Authors: Kincaid Rodney P. , Sullivan Christopher S. 
Published: March 2016

ABSTRACT

Despite increasing interest in the biology of noncoding RNAs (ncRNAs), few functions have been uncovered for viral ncRNAs
in vivo
. In their recent article in
mSphere
, Feldman and colleagues [E. R. Feldman et al.,
mSphere
1(2):e00105-15, 2016, doi:
10.1128/mSphere.00105-15
] demonstrate a highly specific activity of a gammaherpesviral ncRNA in viral dissemination and establishment of latent infection. Their work highlights several interesting features that should be informative to future studies of viral ncRNA.
RbdB, a Rhomboid Protease Critical for SREBP Activation and Virulence in
Aspergillus fumigatus
Authors: Dhingra Sourabh , Kowalski Caitlin H. , Thammahong Arsa , Beattie Sarah R. , Bultman Katherine M. , Cramer Robert A. 
Published: March 2016

Aspergillus fumigatus
causes life-threatening infections, and treatment options remain limited. Thus, there is an urgent need to find new therapeutic targets to treat this deadly disease. Previously, we have shown that SREBP transcription factors and their regulatory components are critical for the pathobiology of
A. fumigatus
. Here we identify a role for RbdB, a rhomboid protease, as an essential component of SREBP activity. Our results indicate that mutants lacking
rbdB
have growth defects under hypoxic conditions, are hypersusceptible to voriconazole, lack extracellular siderophore production, and fail to cause disease in a murine model of invasive pulmonary aspergillosis. This study increases our understanding of the molecular mechanisms involved in SREBP activation in pathogenic fungi and provides a novel therapeutic target for future development.