bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing the Limits of Welfare State Changes: The Slow‐moving Immigration Policy Reform in Japan
Authors: Peng Ito 
Published: February 2016

AbstractIn the 1990s, the Japanese government made transformative policy change by significantly expanding social care, thereby contradicting the core of the country's familialistic welfare principle of non‐state intervention in the family. Remarkably, social care expansions were widely accepted by the public as necessary, if not welcome, changes to deal with low fertility and an ageing society. Japanese people seemed to have no problem accepting that the rapid demographic ageing and the ‘modernization’ of the family necessitated outsourcing childcare and elder care. As the supply of native‐born care workers continued to shrink, the Japanese government began turning to foreign care workers. Unlike the case of social care expansion, however, immigration policy changes are proving difficult. Despite ample motivations, opportunities, and positive political mobilization, policy reforms have been slow and are far from achieving their goals. Most Japanese citizens are highly ambivalent about opening up the country to immigration, and the idea of immigration and multicultural societies remains disconnected from that of a shared national identity premised on ethnic and cultural homogeneity. This article shows the importance of public sentiments and national collective imaginary in policy change.
Prior antibacterial drug exposure in dogs with meticillin‐resistant Staphylococcus pseudintermedius (MRSP) pyoderma
Authors: Hensel Nao , Zabel Sonja , Hensel Patrick 
Published: February 2016

BackgroundThe emergence of meticillin‐resistant Staphylococcus pseudintermedius (MRSP) has become a significant animal health problem. Recent studies have indicated that previous antibacterial drug exposure is a factor in acquisition of meticillin‐resistant strains of staphylococci.Hypothesis/ObjectivesThe purpose of this study was to identify factors associated with prior antimicrobial drug use and MRSP pyoderma in dogs presented to a veterinary teaching hospital.AnimalsDogs diagnosed with pyoderma associated with MRSP (n = 53) or meticillin‐sensitive S. pseudintermedius (MSSP; n = 45).MethodsThe medical records of dogs diagnosed with pyoderma associated with isolation of S. pseudintermedius between January 2006 and November 2012 were reviewed. All cases with a complete twelve month to 3 yr drug history prior to the diagnosis were included.ResultsFifty two of 53 (98%) MRSP cases and 42 of 45 (93%) MSSP cases had received at least one course of antibacterial drug prior to diagnosis. The total number of antibacterial drug prescriptions provided to pet owners and the variety of antibacterial drug classes represented were higher for cases with MRSP than for cases with MSSP (P < 0.0001 and P = 0.009, respectively). More cases with MRSP (98%) received beta‐lactam drugs than those with MSSP (82%; P = 0.007) and the proportion of MRSP cases that had received concurrent immunomodulatory therapy was higher (62% versus 42%; P = 0.048).Conclusions and clinical importanceThese results suggest that the total number of antibacterial drug prescriptions, exposure to multiple drug classes (beta‐lactams in particular) and concurrent immunomodulatory therapy may be associated with increased risk for acquisition of MRSP.
Biomechanical Comparison of Locking Compression Plate and Limited Contact Dynamic Compression Plate Combined with an Intramedullary Rod in a Canine Femoral Fracture‐Gap Model
Authors: Matres‐Lorenzo Luis , Diop Amadou , Maurel Nathalie , Boucton Marie‐Charlotte , Bernard Fabrice , Bernardé Antoine 
Published: February 2016

ObjectiveTo compare the biomechanical properties of locking compression plate (LCP) and a limited contact dynamic compression plate combined with an intramedullary rod (LC‐DCP‐R) in a cadaveric, canine, femoral fracture‐gap model.Study DesignIn vitro biomechanical study; nonrandomized, complete block (dog).Sample PopulationPaired cadaveric canine femora (n = 10 dogs).MethodsPaired femurs with a mid‐diaphyseal 20 mm gap were stabilized with either LCP or LC‐DCP‐R. Nondestructive testing up to 60% of body weight (BW) was followed by a continuous destructive test. Comparative structural properties, 3‐dimensional (3D) interfragmentary motion, and plate linear strain were evaluated. Paired comparisons were made between LCP and LC‐DCP‐R.ResultsStiffness after nondestructive testing was significantly lower for LCP with a mean (95% confidence interval [CI]) of 61 N/mm (46–76) versus 89 N/mm (67–110) for LC‐DCP‐R (P = .0072). Ultimate load to failure was significantly lower for LCP with a median (interquartile range [IQR]) of 270 N (247–286) versus 371.5 (353–385) for LC‐DCP‐R (P = .002). Axial motion at 60% BW was significantly higher for LCP with a median (IQR) of 1.01 mm (0.71–1.26) versus 0.36 mm (0.20–0.49) for LC‐DCP‐R (P = .002). Shear motion was significantly higher for LCP with a median (IQR) of 1.18 (0.78–1.58) versus 0.72 mm (0.45–1.00) for LC‐DCP‐R (P = .018). Strain was significantly higher for mid‐LCP surface with a mean (95%CI) at 60% BW of 979 μdef (579–1378) versus 583 μdef (365–801) at mid‐LC‐DCP‐R surface (P = .0153). The elastic limit strain of the plates was not different and was reached at a mean (95%CI) load of 241 N (190–292) for LCP versus 290 N (245–336) for LC‐DCP‐R (P = .12).ConclusionThe LC‐DCP‐R showed higher stiffness and resistance to failure, lower interfragmentary motion, and lower plate strain and stress compared to LCP.
Reducing streak artifacts in computed tomography via sparse representation in coupled dictionaries
Authors: Karimi Davood , Ward Rabab 
Published: February 2016

Purpose:Reducing the number of acquired projections is a simple and efficient way to reduce the radiation dose in computed tomography (CT). Unfortunately, this results in streak artifacts in the reconstructed images that can significantly reduce their diagnostic value. This paper presents a novel algorithm for suppressing these artifacts in 3D CT.Methods:The proposed algorithm is based on the sparse representation of small blocks of 3D CT images in learned overcomplete dictionaries. It learns two dictionaries, the first dictionary (Da) is for artifact‐full images that have been reconstructed from a small number (approximately 100) of projections. The other dictionary (Dc) is for clean artifact‐free images. The core idea behind the proposed algorithm is to relate the representation coefficients of an artifact‐full block in Da to the representation coefficients of the corresponding artifact‐free block in Dc. The relation between these coefficients is modeled with a linear mapping. The two dictionaries and the linear relation between the coefficients are learned simultaneously from the training data. To remove the artifacts from a test image, small blocks are extracted from this image and their sparse representation is computed in Da. The linear map is then used to compute the corresponding coefficients in Dc, which are then used to produce the artifact‐suppressed blocks.Results:The authors apply the proposed algorithm on real cone‐beam CT images. Their results show that the proposed algorithm can effectively suppress the artifacts and substantially improve the quality of the reconstructed images. The images produced by the proposed algorithm have a higher quality than the images reconstructed by the FDK algorithm from twice as many projections.Conclusions:The proposed sparsity‐based algorithm can be a valuable tool for postprocessing of CT images reconstructed from a small number of projections. Therefore, it has the potential to be an effective tool for low‐dose CT.
Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System
Authors: Demers Anne-Marie , Venter Amour , Friedrich Sven O. , Rojas-Ponce Gabriel , Mapamba Daniel , Jugheli Levan , Sasamalo Mohammed , Almeida Deepak , Dorasamy Afton , Jentsch Ute , Gibson Mara , Everitt Daniel , Eisenach Kathleen D. , Diacon Andreas H. 
Published: February 2016

ABSTRACT
Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens.
Commentary: Revisiting the Roles of Culture and Culture-Independent Detection Tests for Campylobacter
Authors: Couturier Marc Roger 
Published: February 2016

ABSTRACT

Culture-independent detection tests (CIDTs) for
Campylobacter
have become an area of intense controversy and confusion among laboratorians in the field of clinical microbiology. To date, the true analytical and clinical performance of stool antigen CIDTs versus truly optimized culture conditions is unknown. In this issue of the
Journal of Clinical Microbiology
, Fitzgerald and colleagues (C. Fitzgerald et al., J Clin Microbiol 54:1209–1215, 2016,
http://dx.doi.org/10.1128/JCM.01925-15
) report comprehensive performance data for four
Campylobacter
stool antigen CIDTs versus culture and molecular diagnostics.
Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle
Authors: Gniadek Thomas J. , Carroll Karen C. , Simner Patricia J. 
Published: February 2016

ABSTRACT

The non-glucose-fermenting Gram-negative bacilli
Pseudomonas aeruginosa
and
Acinetobacter baumannii
are increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF.
Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer Composition and Protein Lipidation
Authors: Barros Marilia , Heinrich Frank , Datta Siddhartha A. K. , Rein Alan , Karageorgos Ioannis , Nanda Hirsh , Lösche Mathias 
Published: February 2016

ABSTRACT

By assembling in a protein lattice on the host's plasma membrane, the retroviral Gag polyprotein triggers formation of the viral protein/membrane shell. The MA domain of Gag employs multiple signals—electrostatic, hydrophobic, and lipid-specific—to bring the protein to the plasma membrane, thereby complementing protein-protein interactions, located in full-length Gag, in lattice formation. We report the interaction of myristoylated and unmyristoylated HIV-1 Gag MA domains with bilayers composed of purified lipid components to dissect these complex membrane signals and quantify their contributions to the overall interaction. Surface plasmon resonance on well-defined planar membrane models is used to quantify binding affinities and amounts of protein and yields free binding energy contributions, Δ
G
, of the various signals. Charge-charge interactions in the absence of the phosphatidylinositide PI(4,5)P
2
attract the protein to acidic membrane surfaces, and myristoylation increases the affinity by a factor of 10; thus, our data do not provide evidence for a PI(4,5)P
2
trigger of myristate exposure. Lipid-specific interactions with PI(4,5)P
2
, the major signal lipid in the inner plasma membrane, increase membrane attraction at a level similar to that of protein lipidation. While cholesterol does not directly engage in interactions, it augments protein affinity strongly by facilitating efficient myristate insertion and PI(4,5)P
2
binding. We thus observe that the isolated MA protein, in the absence of protein-protein interaction conferred by the full-length Gag, binds the membrane with submicromolar affinities.

IMPORTANCE
Like other retroviral species, the Gag polyprotein of HIV-1 contains three major domains: the N-terminal, myristoylated MA domain that targets the protein to the plasma membrane of the host; a central capsid-forming domain; and the C-terminal, genome-binding nucleocapsid domain. These domains act in concert to condense Gag into a membrane-bounded protein lattice that recruits genomic RNA into the virus and forms the shell of a budding immature viral capsid. In binding studies of HIV-1 Gag MA to model membranes with well-controlled lipid composition, we dissect the multiple interactions of the MA domain with its target membrane. This results in a detailed understanding of the thermodynamic aspects that determine membrane association, preferential lipid recruitment to the viral shell, and those aspects of Gag assembly into the membrane-bound protein lattice that are determined by MA.
Role of N Terminus-Truncated NS1 Proteins of Influenza A Virus in Inhibiting IRF3 Activation
Authors: Kuo Rei-Lin , Li Li-Hsin , Lin Sue-Jane , Li Zong-Hua , Chen Guang-Wu , Chang Cheng-Kai , Wang Yi-Ren , Tam Ee-Hong , Gong Yu-Nong , Krug Robert M. , Shih Shin-Ru 
Published: February 2016

ABSTRACT
The NS1 protein encoded by influenza A virus antagonizes the interferon response through various mechanisms, including blocking cellular mRNA maturation by binding the cellular CPSF30 3′ end processing factor and/or suppressing the activation of interferon regulatory factor 3 (IRF3). In the present study, we identified two truncated NS1 proteins that are translated from internal AUGs at positions 235 and 241 of the NS1 open reading frame. We analyzed the cellular localization and function of the N-truncated NS1 proteins encoded by two influenza A virus strains, Udorn/72/H3N2 (Ud) and Puerto Rico/8/34/H1N1 (PR8). The NS1 protein of PR8, but not Ud, inhibits the activation of IRF3, whereas the NS1 protein of Ud, but not PR8, binds CPSF30. The truncated PR8 NS1 proteins are localized in the cytoplasm, whereas the full-length PR8 NS1 protein is localized in the nucleus. The infection of cells with a PR8 virus expressing an NS1 protein containing mutations of the two in-frame AUGs results in both the absence of truncated NS1 proteins and the reduced inhibition of activation of IRF3 and beta interferon (IFN-β) transcription. The expression of the truncated PR8 NS1 protein by itself enhances the inhibition of the activation of IRF3 and IFN-β transcription in Ud virus-infected cells. These results demonstrate that truncated PR8 NS1 proteins contribute to the inhibition of activation of this innate immune response. In contrast, the N-truncated NS1 proteins of the Ud strain, like the full-length NS1 protein, are localized in the nucleus, and mutation of the two in-frame AUGs has no effect on the activation of IRF3 and IFN-β transcription.

IMPORTANCE
Influenza A virus causes pandemics and annual epidemics in the human population. The viral NS1 protein plays a critical role in suppressing type I interferon expression. In the present study, we identified two novel truncated NS1 proteins that are translated from the second and third in-frame AUG codons in the NS1 open reading frame. The N-terminally truncated NS1 encoded by the H1N1 PR8 strain of influenza virus that suppresses IRF3 activation is localized primarily in the cytoplasm. We demonstrate that this truncated NS1 protein by itself enhances this suppression, demonstrating that some strains of influenza A virus express truncated forms of the NS1 protein that function in the inhibition of cytoplasmic antiviral events.
Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z
Authors: Hastie Kathryn M. , Zandonatti Michelle , Liu Tong , Li Sheng , Woods Virgil L. , Saphire Erica Ollmann 
Published: February 2016

ABSTRACT
The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z.

IMPORTANCE
The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a “wreath” with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted.
Mapping Antigenic Epitopes on the Human Bocavirus Capsid
Authors: Kailasan Shweta , Garrison Jamie , Ilyas Maria , Chipman Paul , McKenna Robert , Kantola Kalle , Söderlund-Venermo Maria , Kučinskaitė-Kodzė Indrė , Žvirblienė Aurelija , Agbandje-McKenna Mavis 
Published: February 2016

ABSTRACT

Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in
Parvoviridae
. The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses.

IMPORTANCE
Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.
Dynamics of Chikungunya Virus Cell Entry Unraveled by Single-Virus Tracking in Living Cells
Authors: Hoornweg Tabitha E. , van Duijl-Richter Mareike K. S. , Ayala Nuñez Nilda V. , Albulescu Irina C. , van Hemert Martijn J. , Smit Jolanda M. 
Published: February 2016

ABSTRACT
Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in Africa, Asia, and the Americas. The cell entry pathway hijacked by CHIKV to infect a cell has been studied previously using inhibitory compounds. There has been some debate on the mechanism by which CHIKV enters the cell: several studies suggest that CHIKV enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. Here we applied live-cell microscopy and monitored the cell entry behavior of single CHIKV particles in living cells transfected with fluorescent marker proteins. This approach allowed us to obtain detailed insight into the dynamic events that occur during CHIKV entry. We observed that almost all particles fused within 20 min after addition to the cells. Of the particles that fused, the vast majority first colocalized with clathrin. The average time from initial colocalization with clathrin to the moment of membrane fusion was 1.7 min, highlighting the rapidity of the cell entry process of CHIKV. Furthermore, these results show that the virus spends a relatively long time searching for a receptor. Membrane fusion was observed predominantly from within Rab5-positive endosomes and often occurred within 40 s after delivery to endosomes. Furthermore, we confirmed that a valine at position 226 of the E1 protein enhances the cholesterol-dependent membrane fusion properties of CHIKV. To conclude, our work confirms that CHIKV enters cells via clathrin-mediated endocytosis and shows that fusion occurs from within acidic early endosomes.

IMPORTANCE
Since its reemergence in 2004, chikungunya virus (CHIKV) has spread rapidly around the world, leading to millions of infections. CHIKV often causes chikungunya fever, a self-limiting febrile illness with severe arthralgia. Currently, no vaccine or specific antiviral treatment against CHIKV is available. A potential antiviral strategy is to interfere with the cell entry process of the virus. However, conflicting results with regard to the cell entry pathway used by CHIKV have been published. Here we applied a novel technology to visualize the entry behavior of single CHIKV particles in living cells. Our results show that CHIKV cell entry is extremely rapid and occurs via clathrin-mediated endocytosis. Membrane fusion from within acidic early endosomes is observed. Furthermore, the membrane fusion capacity of CHIKV is strongly promoted by cholesterol in the target membrane. Taking these findings together, this study provides detailed insight into the cell entry process of CHIKV.