bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tales of dracula ants: the evolutionary history of the ant subfamily Amblyoponinae (Hymenoptera: Formicidae)
Authors: WARD PHILIP S. , FISHER BRIAN L. 
Published: June 2016

AbstractThe ants in the subfamily Amblyoponinae are an old, relictual group with an unusual suite of morphological and behavioural features. Adult workers pierce the integument of their larvae to imbibe haemolymph, earning them the vernacular name ‘dracula ants’. We investigate the phylogeny of this group with a data set based on 54 ingroup taxa, 23 outgroups and 11 nuclear gene fragments (7.4 kb). We find that the genus Opamyrma has been misplaced in this subfamily: it is a member of the leptanilline clade and sister to all other extant Leptanillinae. Transfer of Opamyrma to Leptanillinae renders the Amblyoponinae monophyletic. The enigmatic Afrotropical genus Apomyrma is sister to all other amblyoponines, and the latter cleave into two distinct and well‐supported clades, here termed POA and XMMAS. The POA clade, containing Prionopelta, Onychomyrmex and Amblyopone, is well resolved internally, and its structure supports synonymy of the genus Concoctio under Prionopelta (syn.n.). The XMMAS clade comprises two well‐supported groups: (i) a predominantly Neotropical clade, for which we resurrect the genus name Fulakora (stat.r., stat.n.), with junior synonyms Paraprionopelta (syn.n.) and Ericapelta (syn.n.); and (ii) the remaining taxa, or ‘core XMMAS’, which are manifested in our study as a poorly resolved bush of about a dozen lineages, suggesting rapid radiation at the time of their origin. Most of these XMMAS lineages have been assigned to the catch‐all genus Stigmatomma, but the more distinctive elements have been treated as separate genera (Xymmer, Mystrium, Myopopone and Adetomyrma). Resolution of basal relationships in the core XMMAS clade and reconfiguration of ‘Stigmatomma’ to restore monophyly of all named genera will require more extensive genetic data and additional morphological analysis. However, the genus Bannapone can be synonymized under Stigmatomma (syn.n.) because it is embedded within a clade that contains S. denticulatum, the type species of Stigmatomma. Divergence dating analysis indicates that crown Amblyoponinae arose in the mid‐Cretaceous, about 107 Ma (95% highest probability density: 93–121 Ma). The POA and XMMAS clades have estimated crown ages of 47 and 73 Ma, respectively. The initial burst of diversification in the core XMMAS clade occurred in the Late Paleocene/Early Eocene (50–60 Ma). Ancestral range reconstruction suggests that amblyoponines originated in the Afrotropics, and dispersed to the Indo‐Malayan region and to the New World. During none of these dispersal events did the ants break out of their cryptobiotic lifestyle.
Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients – an economic evaluation
Authors: Okerberg C. K. , Williams L. A. , Kilgore M. L. , Kim C. H. , Marques M. B. , Schwartz J. , Pham H. P. 
Published: June 2016

BackgroundFibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding.MethodsWe created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15–20 cryo units or 3–4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted.ResultsAfter adjusting for 28% wastage and technologist salary, cryo cost is $414/5‐unit pool. Depending on the dose, FC is more expensive by $976‐$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25–0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off‐label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount.ConclusionFibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.
The linear programming relaxation permutation symmetry group of an orthogonal array defining integer linear program
Authors: Arquette David M. , Bulutoglu Dursun A. 
Published: June 2016

There is always a natural embedding of $S_{s}\wr S_{k}$ into the linear programming (LP) relaxation permutation symmetry group of an orthogonal array integer linear programming (ILP) formulation with equality constraints. The point of this paper is to prove that in the $2$-level, strength-$1$ case the LP relaxation permutation symmetry group of this formulation is isomorphic to $S_{2}\wr S_{k}$ for all $k$, and in the $2$-level, strength-$2$ case it is isomorphic to $S_{2}^{k}\rtimes S_{k+1}$ for $k\geqslant 4$. The strength-$2$ result reveals previously unknown permutation symmetries that cannot be captured by the natural embedding of $S_{2}\wr S_{k}$. We also conjecture a complete characterization of the LP relaxation permutation symmetry group of the ILP formulation.Supplementary materials are available with this article.
Conformal image‐guided microbeam radiation therapy at the ESRF biomedical beamline ID17
Authors: Donzelli Mattia , Bräuer‐Krisch Elke , Nemoz Christian , Brochard Thierry , Oelfke Uwe 
Published: June 2016

Purpose:Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep‐seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target.Methods:This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x‐ray projection images from different angles.Results:Using four external fiducial markers of 1.7  mm diameter and computed tomography‐based treatment planning, a target alignment error of less than 2  mm can be achieved with an angular deviation of less than 2∘. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1  mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam.Conclusions:The ESRF biomedical beamline ID17 is technically ready to apply conformal image‐guided MRT from multiple ports to large animals during future veterinary trials.
Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning
Authors: Kulmala Jenni , Ngandu Tiia , Pajala Satu , Lehtisalo Jenni , Levälahti Esko , Antikainen Riitta , Laatikainen Tiina , Oksa Heikki , Peltonen Markku , Rauramaa Rainer , Soininen Hilkka , Strandberg Timo , Tuomilehto Jaakko , Kivipelto Miia 
Published: June 2016

Background:Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning.Methods:The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants’ data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning.Results:A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24–0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27–0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22–2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14–2.69) and poorer walking speed (β = .10, P = .005).Conclusions:This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work.
Objectively Assessed Physical Activity and Associated Factors Among Adults in Peri-Urban and Rural Eastern Uganda: A Population-based Study
Authors: Kirunda Barbara Eva , Wamani Henry , Fadnes Lars Thore , Van den Broeck Jan , Tylleskär Thorkild 
Published: June 2016

Background:Data on physical inactivity, a known risk factor for noncommunicable diseases and its correlates in sub-Saharan Africa are almost absent. We assessed physical activity patterns and associated factors among adults.Methods:A populationbased study of 1208 adults was conducted in the Iganga-Mayuge Health and Demographic Surveillance Site, Uganda. Physical activity was assessed using a pedometer for 7 days. Physical inactivity was defined as a daily average of < 7500 steps while sedentary behavior was defined as a daily average of < 5000 steps. Logistic regression was conducted to identify factors associated with physical inactivity and sedentary behavior.Results:Of the 1208 participants, 18.8% were sedentary (10.6% of men; 26.9% of women, P < .001), 37.6% were physically inactive (28.5% of men; 46.6% of women, P < .001). Factors associated with sedentary behavior were being female, ≥ 65 years, peri-urban residence, being a domestic worker, formal employment and lower primary education. Factors associated with physical inactivity were being female, 55 to 64 years, ≥ 65 years, peri-urban residence, overweight and obesity.Conclusions:Sedentary behavior and physical inactivity were prevalent among the adult population. Targeted physical activity promotion interventions are needed.
Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States
Authors: Mirajkar Nandita S. , Davies Peter R. , Gebhart Connie J. 
Published: June 2016

ABSTRACT

Outbreaks of swine dysentery, caused by
Brachyspira hyodysenteriae
and the recently discovered “
Brachyspira hampsonii
,” have reoccurred in North American swine herds since the late 2000s. Additionally, multiple
Brachyspira
species have been increasingly isolated by North American diagnostic laboratories. In Europe, the reliance on antimicrobial therapy for control of swine dysentery has been followed by reports of antimicrobial resistance over time. The objectives of our study were to determine the antimicrobial susceptibility trends of four
Brachyspira
species originating from U.S. swine herds and to investigate their associations with the bacterial species, genotypes, and epidemiological origins of the isolates. We evaluated the susceptibility of
B. hyodysenteriae
,
B. hampsonii
,
Brachyspira pilosicoli
, and
Brachyspira murdochii
to tiamulin, valnemulin, doxycycline, lincomycin, and tylosin by broth microdilution and that to carbadox by agar dilution. In general,
Brachyspira
species showed high susceptibility to tiamulin, valnemulin, and carbadox, heterogeneous susceptibility to doxycycline, and low susceptibility to lincomycin and tylosin. A trend of decreasing antimicrobial susceptibility by species was observed (
B. hampsonii
>
B. hyodysenteriae
>
B. murdochii
>
B. pilosicoli
). In general,
Brachyspira
isolates from the United States were more susceptible to these antimicrobials than were isolates from other countries. Decreased antimicrobial susceptibility was associated with the genotype, stage of production, and production system from which the isolate originated, which highlights the roles of biosecurity and husbandry in disease prevention and control. Finally, this study also highlights the urgent need for Clinical and Laboratory Standards Institute-approved clinical breakpoints for
Brachyspira
species, to facilitate informed therapeutic and control strategies.
Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS
Authors: He Zhenjian , Zhu Xun , Wen Weitao , Yuan Jie , Hu Yiwen , Chen Jiahui , An Shu , Dong Xinhuai , Lin Cuiji , Yu Jianchen , Wu Jueheng , Yang Yi , Cai Junchao , Li Jun , Li Mengfeng 
Published: June 2016

ABSTRACT
Dengue virus (DENV) is the most common mosquito-borne virus infecting humans and is currently a serious global health challenge. To establish infection in its host cells, DENV must subvert the production and/or antiviral effects of interferon (IFN). The aim of this study was to understand the mechanisms by which DENV suppresses IFN production. We determined that DENV NS4A interacts with mitochondrial antiviral signaling protein (MAVS), which was previously found to activate NF-κB and IFN regulatory factor 3 (IRF3), thus inducing type I IFN in the mitochondrion-associated endoplasmic reticulum membranes (MAMs). We further demonstrated that NS4A is associated with the N-terminal CARD-like (CL) domain and the C-terminal transmembrane (TM) domain of MAVS. This association prevented the binding of MAVS to RIG-I, resulting in the repression of RIG-I-induced IRF3 activation and, consequently, the abrogation of IFN production. Collectively, our findings illustrate a new molecular mechanism by which DENV evades the host immune system and suggest new targets for anti-DENV strategies.

IMPORTANCE
Type I interferon (IFN) constitutes the first line of host defense against invading viruses. To successfully establish infection, dengue virus (DENV) must counteract either the production or the function of IFN. The mechanism by which DENV suppresses IFN production is poorly understood and characterized. In this study, we demonstrate that the DENV NS4A protein plays an important role in suppressing interferon production through binding MAVS and disrupting the RIG-I–MAVS interaction in mitochondrion-associated endoplasmic reticulum membranes (MAMs). Our study reveals that MAVS is a novel host target of NS4A and provides a molecular mechanism for DENV evasion of the host innate immune response. These findings have important implications for understanding the pathogenesis of DENV and may provide new insights into using NS4A as a therapeutic and/or prevention target.
Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection
Authors: Tran Si C. , Pham Tu M. , Nguyen Lam N. , Park Eun-Mee , Lim Yun-Sook , Hwang Soon B. 
Published: June 2016

ABSTRACT

Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and ultimately hepatocellular carcinoma. However, the mechanisms underlying HCV-induced liver pathogenesis are still not fully understood. By transcriptome sequencing (RNA-Seq) analysis, we recently identified host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these, tribbles homolog 3 (TRIB3) was selected for further characterization. TRIB3 was initially identified as a binding partner of protein kinase B (also known as Akt). TRIB3 blocks the phosphorylation of Akt and induces apoptosis under endoplasmic reticulum (ER) stress conditions. HCV has been shown to enhance Akt phosphorylation for its own propagation. In the present study, we demonstrated that both mRNA and protein levels of TRIB3 were increased in the context of HCV replication. We further showed that promoter activity of TRIB3 was increased by HCV-induced ER stress. Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased HCV replication. By employing an HCV pseudoparticle entry assay, we further showed that TRIB3 was a negative host factor involved in HCV entry. Both
in vitro
binding and immunoprecipitation assays demonstrated that HCV NS3 specifically interacted with TRIB3. Consequently, the association of TRIB3 and Akt was disrupted by HCV NS3, and thus, TRIB3-Akt signaling was impaired in HCV-infected cells. Moreover, HCV modulated TRIB3 to promote extracellular signal-regulated kinase (ERK) phosphorylation, activator protein 1 (AP-1) activity, and cell migration. Collectively, these data indicate that HCV exploits the TRIB3-Akt signaling pathway to promote persistent viral infection and may contribute to HCV-mediated pathogenesis.

IMPORTANCE
TRIB3 is a pseudokinase protein that acts as an adaptor in signaling pathways for important cellular processes. So far, the functional involvement of TRIB3 in virus-infected cells has not yet been demonstrated. We showed that both mRNA and protein expression levels of TRIB3 were increased in the context of HCV RNA replication. Gene silencing of TRIB3 increased HCV RNA and protein levels, and thus, overexpression of TRIB3 decreased HCV replication. TRIB3 is known to promote apoptosis by negatively regulating the Akt signaling pathway under ER stress conditions. Most importantly, we demonstrated that the TRIB3-Akt signaling pathway was disrupted by NS3 in HCV-infected cells. These data provide evidence that HCV modulates the TRIB3-Akt signaling pathway to establish persistent viral infection.
Ebola Virus Does Not Induce Stress Granule Formation during Infection and Sequesters Stress Granule Proteins within Viral Inclusions
Authors: Nelson Emily V. , Schmidt Kristina M. , Deflubé Laure R. , Doğanay Sultan , Banadyga Logan , Olejnik Judith , Hume Adam J. , Ryabchikova Elena , Ebihara Hideki , Kedersha Nancy , Ha Taekjip , Mühlberger Elke 
Published: June 2016

ABSTRACT
A hallmark of Ebola virus (EBOV) infection is the formation of viral inclusions in the cytoplasm of infected cells. These viral inclusions contain the EBOV nucleocapsids and are sites of viral replication and nucleocapsid maturation. Although there is growing evidence that viral inclusions create a protected environment that fosters EBOV replication, little is known about their role in the host response to infection. The cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation and translational arrest mediated by the phosphorylation of a translation initiation factor, the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we show that selected SG proteins are sequestered within EBOV inclusions, where they form distinct granules that colocalize with viral RNA. These inclusion-bound (IB) granules are functionally and structurally different from canonical SGs. Formation of IB granules does not indicate translational arrest in the infected cells. We further show that EBOV does not induce formation of canonical SGs or eIF2α phosphorylation at any time postinfection but is unable to fully inhibit SG formation induced by different exogenous stressors, including sodium arsenite, heat, and hippuristanol. Despite the sequestration of SG marker proteins into IB granules, canonical SGs are unable to form within inclusions, which we propose might be mediated by a novel function of VP35, which disrupts SG formation. This function is independent of VP35's RNA binding activity. Further studies aim to reveal the mechanism for SG protein sequestration and precise function within inclusions.

IMPORTANCE
Although progress has been made developing antiviral therapeutics and vaccines against the highly pathogenic Ebola virus (EBOV), the cellular mechanisms involved in EBOV infection are still largely unknown. To better understand these intracellular events, we investigated the cellular stress response, an antiviral pathway manipulated by many viruses. We show that EBOV does not induce formation of stress granules (SGs) in infected cells and is therefore unrestricted by their concomitant translational arrest. We identified SG proteins sequestered within viral inclusions, which did not impair protein translation. We further show that EBOV is unable to block SG formation triggered by exogenous stress early in infection. These findings provide insight into potential targets of therapeutic intervention. Additionally, we identified a novel function of the interferon antagonist VP35, which is able to disrupt SG formation.
Mutants at the 2-Fold Interface of Adeno-associated Virus Type 2 (AAV2) Structural Proteins Suggest a Role in Viral Transcription for AAV Capsids
Authors: Aydemir Fikret , Salganik Maxim , Resztak Justyna , Singh Jasbir , Bennett Antonette , Agbandje-McKenna Mavis , Muzyczka Nicholas 
Published: June 2016

ABSTRACT

We previously reported that an amino acid substitution, Y704A, near the 2-fold interface of adeno-associated virus (AAV) was defective for transcription of the packaged genome (M. Salganik, F. Aydemir, H. J. Nam, R. McKenna, M. Agbandje-McKenna, and N. Muzyczka, J Virol 88:1071–1079, 2013, doi:
http://dx.doi.org/10.1128/JVI.02093-13
). In this report, we have characterized the defect in 6 additional capsid mutants located in a region ∼30 Å in diameter on the surface of the AAV type 2 (AAV2) capsid near the 2-fold interface. These mutants, which are highly conserved among primate serotypes, displayed a severe defect (3 to 6 logs) in infectivity. All of the mutants accumulated significant levels of uncoated DNA in the nucleus, but none of the mutants were able to accumulate significant amounts of genomic mRNA postinfection. In addition, wild-type (wt) capsids that were bound to the conformational antibody A20, which is known to bind the capsid surface in the region of the mutants, were also defective for transcription. In all cases, the mutant virus particles, as well as the antibody-bound wild-type capsids, were able to enter the cell, travel to the nucleus, uncoat, and synthesize a second strand but were unable to transcribe their genomes. Taken together, the phenotype of these mutants provides compelling evidence that the AAV capsid plays a role in the transcription of its genome, and the mutants map this functional region on the surface of the capsid near the 2-fold interface. This appears to be the first example of a viral structural protein that is also involved in the transcription of the viral genome that it delivers to the nucleus.

IMPORTANCE
Many viruses package enzymes within their capsids that assist in expressing their genomes postinfection, e.g., retroviruses. A number of nonenveloped viruses, including AAV, carry proteases that are needed for capsid maturation or for capsid modification during infection. We describe here what appears to be the first example of a nonenveloped viral capsid that appears to have a role in promoting transcription. A total of six mutants at the AAV capsid 2-fold interface were shown to have a severe defect in expressing their genomes, and the defect was at the level of mRNA accumulation. This suggests that AAV capsids have a novel role in promoting the transcription of the genomes that they have packaged. Since wt virions could not complement the mutant viruses, and the mutant viruses did not effectively inhibit wt gene expression, our results suggest that the capsid exerts its effect on transcription in
cis
.