bluuebunny/crossref_metadata_2025 huggingface dataset:
QUALITY OF LIFE OF KIDNEY DONORS RESIDING IN KATHMANDU VALLEY
Authors: Shakya Dayana , K.C. Takma
Published: February 2016

Background

Transplantation is evolving as an efficient treatment modality in Nepal for the rising cases of kidney failure. As living donors are healthy people donating their organ for the benefit of the recipient, it is imperative to ensure their safety.

Objectives

To assess the quality of life (QOL) of kidney donors and to compare it with healthy references.

Methodology

Cross‐sectional, comparative design was used to find out the QOL of 59 donors and 59 healthy references. Convenience sampling was used to approach donors and eligible donors were interviewed at their residences. These were compared with age‐ and sex‐matched references. QOL was assessed using SF36v2.

Result

Male, educated and employed donors were found to have better QOL than their counterparts. The comparison of donors and references showed better scores in the donors’ QOL with significant differences in general health, mental health and mental component score.

Conclusion

This study concludes that living kidney donation does not impair the QOL of the donors but in turn may improve their mental health. Hence, this study supports the practice of living‐related kidney transplantation.

Implications

Besides providing baseline data about donors in Nepal, this study may guide health professionals in counselling potential donors and assisting patients and their families to make informed decisions regarding transplant. It can assist health care planners in making policies concerning transplant.
An overview of systematic reviews on the effectiveness of periodontal treatment to improve glycaemic control
Authors: Faggion C. M. , Cullinan M. P. , Atieh M.
Published: February 2016

Several systematic reviews with meta‐analyses on the effectiveness of periodontal treatment to improve glycaemic control have been published. So far no overview of these systematic reviews has been performed. The main objective of this report was to assess critically these systematic reviews to provide the reader with a high‐level synthesis of research evidence. MEDLINE (via PubMed) and EMBASE databases were searched independently and in duplicate to identify systematic reviews with meta‐analyses of clinical studies that assessed the relationship between diabetes mellitus and periodontitis. The last database search was performed on 10 March 2015. The reference lists of included systematic reviews were also scrutinized for further publications. The methodological quality of the included systematic reviews was assessed independently with two validated checklists (AMSTAR and OQAQ) by two authors. Disagreements in the assessment were resolved by consensus. A total of 226 potential publications were initially retrieved. Eleven systematic reviews with meta‐analyses were finally included. Glycosylated haemoglobin A1c (HbA1c) was the most commonly used clinical endpoint. Meta‐analytic estimates from systematic reviews generated an average reduction of 0.46% (median 0.40%) of HbA1c in patients with diabetes mellitus who received periodontal treatment. These meta‐analyses had, nevertheless, methodological limitations such as inclusion of trials with different types of risk of bias that hinder more robust conclusions. A recent meta‐analysis that included recently published large randomized controlled trials did not show significant change in the level of HbA1c at the 6 mo follow‐up. The AMSTAR checklist generated results that were more conservative than OQAQ. Findings from this overview do not support the information that periodontal treatment may improve glycaemic control. Methodological issues described in this overview may guide further research on this topic.
Circuitist and Keynesian Approaches to Money: A Reconciliation?
Authors: Sardoni Claudio
Published: February 2016

Keynesian monetary theory focuses on money as a store of value, seen as a defence against uncertainty. Circuitist economists emphasize the role of money as means of payment and downplay its function of store of value. The paper, by drawing on Hicks's and Kaldor's contributions, suggests an approach in which the fundamental functions of money are those of unit of account and means of payment. The function of money as store of value is regarded as marginal, because in economies with well‐developed financial markets it can be played by other assets as liquid and risk‐less as money. The demand for liquidity as a defence against uncertainty is kept distinct from the demand for money. This approach to money makes it easier to develop a framework in which the Keynesian and circuitist approaches can be reconciled and co‐exist.
An interdomain network: the endobacterium of a mycorrhizal fungus promotes antioxidative responses in both fungal and plant hosts
Authors: Vannini Candida , Carpentieri Andrea , Salvioli Alessandra , Novero Mara , Marsoni Milena , Testa Lorenzo , de Pinto Maria Concetta , Amoresano Angela , Ortolani Francesca , Bracale Marcella , Bonfante Paola
Published: February 2016

Arbuscular mycorrhizal fungi (AMF) are obligate plant biotrophs that may contain endobacteria in their cytoplasm. Genome sequencing of Candidatus Glomeribacter gigasporarum revealed a reduced genome and dependence on the fungal host.

RNA‐seq analysis of the AMF Gigaspora margarita in the presence and absence of the endobacterium indicated that endobacteria have an important role in the fungal pre‐symbiotic phase by enhancing fungal bioenergetic capacity. To improve the understanding of fungal–endobacterial interactions, iTRAQ (isobaric tags for relative and absolute quantification) quantitative proteomics was used to identify differentially expressed proteins in G. margarita germinating spores with endobacteria (B+), without endobacteria in the cured line (B−) and after application of the synthetic strigolactone GR24.

Proteomic, transcriptomic and biochemical data identified several fungal and bacterial proteins involved in interspecies interactions. Endobacteria influenced fungal growth, calcium signalling and metabolism. The greatest effects were on fungal primary metabolism and respiration, which was 50% higher in B+ than in B−. A shift towards pentose phosphate metabolism was detected in B−. Quantification of carbonylated proteins indicated that the B− line had higher oxidative stress levels, which were also observed in two host plants.

This study shows that endobacteria generate a complex interdomain network that affects AMF and fungal–plant interactions.
Obesity prevention at the point of purchase
Authors: Cohen D. A. , Lesser L. I.
Published: February 2016

The point of purchase is when people may make poor and impulsive decisions about what and how much to buy and consume. Because point of purchase strategies frequently work through non‐cognitive processes, people are often unable to recognize and resist them. Because people lack insight into how marketing practices interfere with their ability to routinely eat healthy, balanced diets, public health entities should protect consumers from potentially harmful point of purchase strategies. We describe four point of purchase policy options including standardized portion sizes; standards for meals that are sold as a bundle, e.g. ‘combo meals’; placement and marketing restrictions on highly processed low‐nutrient foods; and explicit warning labels. Adoption of such policies could contribute significantly to the prevention of obesity and diet‐related chronic diseases. We also discuss how the policies could be implemented, along with who might favour or oppose them. Many of the policies can be implemented locally, while preserving consumer choice. © 2016 World Obesity
DOES A PUBLIC SERVICE ETHIC ENCOURAGE ETHICAL BEHAVIOUR? PUBLIC SERVICE MOTIVATION, ETHICAL LEADERSHIP AND THE WILLINGNESS TO REPORT ETHICAL PROBLEMS
Authors: WRIGHT BRADLEY E. , HASSAN SHAHIDUL , PARK JONGSOO
Published: February 2016

This article aims to advance our understanding of and confidence in the relationship between employee public service motivation (PSM) and ethical behaviour by testing the degree to whichPSMpredicts the ethical behaviour or behavioural intention of government employees. Building on previous research, we argue that government employees with higherPSMare not only more likely to internalize values that support public interests, they also are likely to be concerned less about the potential consequences that they may experience by reporting unethical conduct within their agencies. Using data collected through a survey from 477 employees working in a large state agency, we find that supervisors with higherPSMare more likely to be perceived by their subordinates as exhibiting ethical leadership, supervisors exhibiting higher ethical leadership are more likely to have subordinates with higher levels ofPSMand that subordinates with higherPSMexpress a higher willingness to report unethical behaviour within their agency. We discuss implications of these findings for research onPSM.
Social Policy Change: Work–family Tensions in Sweden, Australia and Canada
Authors: Mahon Rianne , Bergqvist Christina , Brennan Deborah
Published: February 2016

The rise of the adult worker family norm across countries of the Organisation for Economic Co‐operation and Development has created challenges for reconciling work and family life as the unpaid work of the female caregiver can no longer be assumed. The article compares childcare arrangements and maternity/parental leave programmes in Sweden, Australia and Canada that attempt to address these challenges. Sweden was an early innovator, establishing the ‘gold standard’ for such arrangements in the form of publicly funded, universally accessible, centre‐based childcare and generously paid parental leave, including a ‘daddy quota’. Yet policy development remains open to contestation and change even here. Australia and Canada have shown a preference for market‐based solutions although each has taken steps towards Swedish style solutions. In particular, Canadian federalism has left space for such experiments at the provincial scale. The broader institutional arrangements embedded in each country have helped to shape the responses. Yet political contestation, enlivened by the transnational flow of ideas (and ideals), has played an important role in shaping the direction and velocity of change. In the first section we develop this argument, beginning with reflections on how to identify the significance of changes, then moving on to explore the role of institutions, actors and ideas in accounting for these developments. Subsequent sections examine developments first in Sweden then Australia and Canada.
Testing the Limits of Welfare State Changes: The Slow‐moving Immigration Policy Reform in Japan
Authors: Peng Ito
Published: February 2016

In 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

Background

The 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/Objectives

The 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.

Animals

Dogs diagnosed with pyoderma associated with MRSP (n = 53) or meticillin‐sensitive S. pseudintermedius (MSSP; n = 45).

Methods

The 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.

Results

Fifty 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 importance

These 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

Objective

To 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 Design

In vitro biomechanical study; nonrandomized, complete block (dog).

Sample Population

Paired cadaveric canine femora (n = 10 dogs).

Methods

Paired 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.

Results

Stiffness 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).

Conclusion

The LC‐DCP‐R showed higher stiffness and resistance to failure, lower interfragmentary motion, and lower plate strain and stress compared to LCP.
A Modified Predictive Functional Control With Sliding Mode Observer for Automated Dry Clutch Control of Vehicle
Authors: Li Liang , Wang Xiangyu , Hu Xiaosong , Chen Zheng , Song Jian , Muhammad Fahad
Published: February 2016

Dry clutch control is a typical nonlinear problem due to the nonlinear characteristics of diaphragm springs. For precise position control of the automated dry clutch, a modified predictive functional control (mPFC) method is proposed. First, a novel mechanical actuator is designed and models of the automated dry clutch system are built based on theoretical analysis and experimental data. Then, in order to compensate for the position error of direct current (DC) motor caused by load torque, modifications are introduced to a regular predictive functional control (PFC), including a sliding mode observer (SMO) to estimate the load torque and a predictive model concerning the load torque. Next, simulations show that the SMO could estimate the load torque accurately and the mPFC performs well with the nonlinear load torque. Finally, experiments are carried out on a test bench and the results are in accordance with the simulations. Due to the little online computing burden and the simple structure of the mPFC, it could be used in other industrial control systems which need fast response.
Investigation of Spiral and Sweeping Holes
Authors: Thurman Douglas , Poinsatte Philip , Ameri Ali , Culley Dennis , Raghu Surya , Shyam Vikram
Published: February 2016

Surface infrared thermography, hotwire anemometry, and thermocouple surveys were performed on two new film cooling hole geometries: spiral/rifled holes and fluidic sweeping holes. The spiral holes attempt to induce large-scale vorticity to the film cooling jet as it exits the hole to prevent the formation of the kidney-shaped vortices commonly associated with film cooling jets. The fluidic sweeping hole uses a passive in-hole geometry to induce jet sweeping at frequencies that scale with blowing ratios. The spiral hole performance is compared to that of round holes with and without compound angles. The fluidic hole is of the diffusion class of holes and is therefore compared to a 777 hole and square holes. A patent-pending spiral hole design showed the highest potential of the nondiffusion-type hole configurations. Velocity contours and flow temperature were acquired at discreet cross sections of the downstream flow field. The passive fluidic sweeping hole shows the most uniform cooling distribution but suffers from low span-averaged effectiveness levels due to enhanced mixing. The data were taken at a Reynolds number of 11,000 based on hole diameter and freestream velocity. Infrared thermography was taken for blowing ratios of 1.0, 1.5, 2.0, and 2.5 at a density ratio of 1.05. The flow inside the fluidic sweeping hole was studied using 3D unsteady Reynolds-average Navier–Stokes (RANS).
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.
Visualizing the molecular sociology at the HeLa cell nuclear periphery
Authors: Mahamid Julia , Pfeffer Stefan , Schaffer Miroslava , Villa Elizabeth , Danev Radostin , Kuhn Cuellar Luis , Förster Friedrich , Hyman Anthony A. , Plitzko Jürgen M. , Baumeister Wolfgang
Published: February 2016

Close-up view of the nuclear periphery

Cell biologists would like to be able to visualize complexes inside cells at molecular resolution. Several limitations, however, have prevented the field from realizing this goal. The thickness of most cells precludes cryo-electron tomography, a technique which itself does not provide sufficient contrast. Mahamid
et al.
successfully combined recent advances on both fronts to analyze structures in situ at the periphery of the nucleus. Their images reveal features that inform our understanding of the native organization of nuclear pores and of the nuclear lamina.

Science
, this issue p.
969
Lewis acids turn unreactive substrates into pure enantiomers
Authors: Dumoulin Audrey , Masson Geraldine
Published: February 2016

Chiral organic anion binding to silyl cation provides a new platform for organocatalysis

[Also see Report by

Gatzenmeier
et al.

]
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

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

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

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

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

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

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

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

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.
APOBEC3G and APOBEC3F Act in Concert To Extinguish HIV-1 Replication
Authors: Krisko John F. , Begum Nurjahan , Baker Caroline E. , Foster John L. , Garcia J. Victor
Published: February 2016

The multifunctional HIV-1 accessory protein Vif counters the antiviral activities of APOBEC3G (A3G) and APOBEC3F (A3F), and some Vifs counter stable alleles of APOBEC3H (A3H). Studies in humanized mice have shown that HIV-1 lacking Vif expression is not viable. Here, we look at the relative contributions of the three APOBEC3s to viral extinction. Inoculation of bone marrow/liver/thymus (BLT) mice with CCR5-tropic HIV-1
JRCSF
(JRCSF) expressing a
vif
gene inactive for A3G but not A3F degradation activity (JRCSFvifH42/43D) displayed either no or delayed replication. JRCSF expressing a
vif
gene mutated to inactivate A3F degradation but not A3G degradation (JRCSFvifW79S) always replicated to high viral loads with variable delays. JRCSF with
vif
mutated to lack both A3G and A3F degradation activities (JRCSFvifH42/43DW79S) failed to replicate, mimicking JRCSF without Vif expression (JRCSFΔvif). JRCSF and JRCSFvifH42/43D, but not JRCSFvifW79S or JRCSFvifH42/43DW79S, degraded APOBEC3D. With one exception, JRCSFs expressing mutant Vifs that replicated acquired enforced
vif
mutations. These mutations partially restored A3G or A3F degradation activity and fully replaced JRCSFvifH42/43D or JRCSFvifW79S by 10 weeks. Surprisingly, induced mutations temporally lagged behind high levels of virus in blood. In the exceptional case, JRCSFvifH42/43D replicated after a prolonged delay with no mutations in
vif
but instead a V27I mutation in the RNase H coding sequence. JRCSFvifH42/43D infections exhibited massive GG/AG mutations in
pol
viral DNA, but in viral RNA, there were no fixed mutations in the Gag or reverse transcriptase coding sequence. A3H did not contribute to viral extinction but, in combination with A3F, could delay JRCSF replication. A3H was also found to hypermutate viral DNA.

IMPORTANCE
Vif degradation of A3G and A3F enhances viral fitness, as virus with even a partially restored capacity for degradation outgrows JRCSFvifH42/43D and JRCSFvifW79S. Unexpectedly, fixation of mutations that replaced H42/43D or W79S in viral RNA lagged behind the appearance of high viral loads. In one exceptional JRCSFvifH42/43D infection,
vif
was unchanged but replication proceeded after a long delay. These results suggest that Vif binds and inhibits the non-cytosine deaminase activities of intact A3G and intact A3F, allowing JRCSFvifH42/43D and JRCSFvifW79S to replicate with reduced fitness. Subsequently, enhanced Vif function is acquired by enforced mutations. In infected cells, JRCSFΔvif and JRCSFvifH42/43DW79S are exposed to active A3F and A3G and fail to replicate. JRCSFvifH42/43D Vif degrades A3F and, in some cases, overcomes A3G mutagenic activity to replicate. Vif may have evolved to inhibit A3F and A3G by stoichiometric binding and subsequently acquired the ability to target these proteins to proteasomes.
Ribosomal Protein Rps26 Influences 80S Ribosome Assembly in Saccharomyces cerevisiae
Authors: Belyy Alexander , Levanova Nadezhda , Tabakova Irina , Rospert Sabine , Belyi Yury
Published: February 2016

Rps26 is an essential protein of the eukaryotic small ribosomal subunit. Previous experiments demonstrated an interaction between the eukaryote-specific Y62–K70 segment of Rps26 and the 5′ untranslated region of mRNA. The data suggested a specific role of the Y62–K70 motif during translation initiation. Here, we report that single-site substitutions within the Y62–K70 peptide did not affect the growth of engineered yeast strains, arguing against its having a critical role during translation initiation via specific interactions with the 5′ untranslated region of mRNA molecules. Only the simultaneous replacement of five conserved residues within the Y62–K70 fragment or the replacement of the yeast protein with the human homolog resulted in growth defects and caused significant changes in polysome profiles. The results expand our knowledge of ribosomal protein function and suggest a role of Rps26 during ribosome assembly in yeast.
Mind the gap: a case of severe methanol intoxication
Authors: Nazir Salik , Melnick Stephen , Ansari Shabana , Kanneh Haitham T
Published: February 2016

We report a case of a 37-year-old woman with non-insulin-dependent diabetes on sitagliptin, an alcohol abuser who was brought unresponsive to the emergency department of our hospital. On arrival, the patient was intubated and mechanically ventilated due to a low Glasgow Coma score of 3/15. Initial laboratory testing identified profound high anion gap metabolic acidosis. Owing to the dubious circumstances and the depth of acidosis, methanol and ethylene glycol intoxication was suspected. Further evaluation revealed a significantly increased serum osmolal gap. Pending volatile compound screen, fomepizole was started and urgent haemodialysis undertaken. Subsequent brain MRI identified changes in putamen of bilateral basal ganglia, suggestive of methanol intoxication. The patient was later found to have an initial methanol level of 237 mg/dL. She was successfully extubated on day 2 of hospitalisation, with residual cognitive and visual deficits.
SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis
Authors: Shyangdan Deepson S , Uthman Olalekan A , Waugh Norman
Published: February 2016

Objective

Because of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.

Design

Systematic review and network meta-analysis.

Data sources

MEDLINE and EMBASE were searched from January 2005 to January 2015.

Eligibility criteria

Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods.

Results

In monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300–2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26).

Conclusions

There were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors.
Multilevel assessment of prenatal engagement in home visiting
Authors: Goyal Neera K , Folger Alonzo T , Hall Eric S , Teeters Angelique , Van Ginkel Judith B , Ammerman Robert T
Published: February 2016

Background

Low engagement in prenatal home visiting may limit programme effectiveness to improve birth outcomes. Multiple factors may influence engagement.

Methods

A retrospective cohort study of first-time mothers enrolled in home visiting prenatally in southwest Ohio from 2007 to 2010. The primary outcome was enrolment by 20weeks’ gestation; a secondary outcome included home visit frequency. Two multilevel assessments were conducted using random intercept multilevel modelling; maternal covariates were nested first within the home visiting agency and then within the ZIP code. In the first model, variations attributable to individual agency and agency volume were assessed. In the second model nested within the ZIP code, violence rates by ZIP code and interaction terms between violence rates and maternal factors were evaluated.

Results

Of 837 women, 25.3% enrolled ≤20 weeks and 7.4% enrolled early and received ≥75% of expected visits. The first model demonstrated a significant variation in early enrolment based on clustering by agency (p<0.001), however, agency volume was not a significant predictor. In the second model, violence rate was not associated with early enrolment (AOR 0.92, p=0.08), but an interaction term with maternal race was significant (p=0.02). The effect of increasing community violence disproportionately affected early enrolment among white women (AOR 0.80, p=0.005) compared with black women (AOR 0.95, p=0.30). In both the random intercept multilevel models, teenagers demonstrated a decreased likelihood of enrolling early (AOR 0.58, p=0.046 and AOR 0.49, p=0.004).

Conclusions

Prenatal home visiting engagement is related to maternal, agency and community factors, presenting multiple opportunities to optimise programme implementation.
Angiotensin-converting enzyme (ACE-I/D) polymorphism frequency in Brazilian soccer players
Authors: Coelho Daniel Barbosa , Pimenta Eduardo , Rosse Izinara Cruz , Veneroso Christiano , Pussieldi Guilherme , Becker Lenice Kapes , Carvalho Maria-Raquel , Silami-Garcia Emerson
Published: February 2016

This study aimed to analyze the angiotensin-converting enzyme (ACE-I/D) allelic and genotypic frequencies in Brazilian soccer players of different ages. The study group comprised 353 players from first-division clubs in the under (U)-14, U-15, U-17, U-20, and professional categories. The allelic and genotypic frequencies did not differ significantly in any of the categories between the group of players and the control group. This was the first study of ACE-I/D polymorphism in Brazilian soccer players.