bluuebunny/crossref_metadata_2025 huggingface dataset:
Escape from bacterial iron piracy through rapid evolution of transferrin
Authors: Barber Matthew F. , Elde Nels C.
Published: December 2014

Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from
Haemophilus influenzae,
revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.
Attosecond band-gap dynamics in silicon
Authors: Schultze Martin , Ramasesha Krupa , Pemmaraju C.D. , Sato S.A. , Whitmore D. , Gandman A. , Prell James S. , Borja L. J. , Prendergast D. , Yabana K. , Neumark Daniel M. , Leone Stephen R.
Published: December 2014

Electron transfer from valence to conduction band states in semiconductors is the basis of modern electronics. Here, attosecond extreme ultraviolet (XUV) spectroscopy is used to resolve this process in silicon in real time. Electrons injected into the conduction band by few-cycle laser pulses alter the silicon XUV absorption spectrum in sharp steps synchronized with the laser electric field oscillations. The observed ~450-attosecond step rise time provides an upper limit for the carrier-induced band-gap reduction and the electron-electron scattering time in the conduction band. This electronic response is separated from the subsequent band-gap modifications due to lattice motion, which occurs on a time scale of 60 ± 10 femtoseconds, characteristic of the fastest optical phonon. Quantum dynamical simulations interpret the carrier injection step as light-field–induced electron tunneling.
67P/Churyumov-Gerasimenko, a Jupiter family comet with a high D/H ratio
Authors: Altwegg K. , Balsiger H. , Bar-Nun A. , Berthelier J. J. , Bieler A. , Bochsler P. , Briois C. , Calmonte U. , Combi M. , De Keyser J. , Eberhardt P. , Fiethe B. , Fuselier S. , Gasc S. , Gombosi T. I. , Hansen K.C. , Hässig M. , Jäckel A. , Kopp E. , Korth A. , LeRoy L. , Mall U. , Marty B. , Mousis O. , Neefs E. , Owen T. , Rème H. , Rubin M. , Sémon T. , Tzou C.-Y. , Waite H. , Wurz P.
Published: December 2014

The provenance of water and organic compounds on Earth and other terrestrial planets has been discussed for a long time without reaching a consensus. One of the best means to distinguish between different scenarios is by determining the deuterium-to-hydrogen (D/H) ratios in the reservoirs for comets and Earth’s oceans. Here, we report the direct in situ measurement of the D/H ratio in the Jupiter family comet 67P/Churyumov-Gerasimenko by the ROSINA mass spectrometer aboard the European Space Agency’s Rosetta spacecraft, which is found to be (5.3 ± 0.7) × 10
−4
—that is, approximately three times the terrestrial value. Previous cometary measurements and our new finding suggest a wide range of D/H ratios in the water within Jupiter family objects and preclude the idea that this reservoir is solely composed of Earth ocean–like water.
The battle for iron
Authors: Armitage Andrew E. , Drakesmith Hal
Published: December 2014

Evolutionary analysis shows how a mammalian iron transport protein evolves to avoid capture by bacteria

[Also see Report by
Barber and Elde
]
Cancer by super-enhancer
Authors: Vähärautio Anna , Taipale Jussi
Published: December 2014

Tiny changes in our genomes can enhance oncogene expression and contribute to tumorigenesis

[Also see Report by

Mansour
et al.

]
Valuing collections
Authors: Kress W. John
Published: December 2014

This year brought dismal news about the world's birds: They are vanishing at an alarming rate. Across 25 European countries, about 420 million fewer birds are present today than in 1980, a 20% decrease, especially in the 36 most common species. In North America,
The State of the Birds Report 2014
indicates that over the past 40 years, the numbers of individuals across 33 species are also down by hundreds of millions. Such assessments highlight the urgency of determining the precise causes of these declines. The knowledge gleaned from the Avian Phylogenomics Project, coupled with ecological and population analyses, should provide new insights into the factors that influence bird declines and extinctions. As the project progresses over the next few years, over 60% of tissue samples for the avian analyses will be derived from archived museum collections. In this era of deteriorating natural environments, a pressing challenge is to continue to build scientific collections for future needs.
Open-Label Trial of Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine in Adults ≥50 Years of Age in Mexico
Authors: Tinoco Juan Carlos , Juergens Christine , Ruiz Palacios Guillermo M. , Vazquez-Narvaez Jorge , Enkerlin-Pauwells Hermann Leo , Sundaraiyer Vani , Pathirana Sudam , Kalinina Elena , Gruber William C. , Scott Daniel A. , Schmoele-Thoma Beate
Published: December 2014

This open-label multicenter clinical trial conducted in Mexico assessed the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥50 years of age not previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). The PCV13 elicited a robust immune response in this study population, as reflected by the magnitude of fold rises in functional antibody levels measured by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination. Although the prevaccination OPA geometric mean titers (GMTs) for the majority of the serotypes were significantly lower in the 50- to 64-year age group than those in the ≥65-year age group, the postvaccination immune responses were generally similar. The overall immune responses were higher for the majority of the serotypes in the Mexican study population than those in similar adult study populations who received the PCV13 in Europe and the United States. PCV13 was well tolerated, and there were no vaccine-related serious adverse events. In conclusion, PCV13 is safe and immunogenic when administered to adults ≥50 years of age in Mexico and has the potential to protect against vaccine-type pneumococcal disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT01432262.)
Geographically Distinct Escherichia coli O157 Isolates Differ by Lineage, Shiga Toxin Genotype, and Total Shiga Toxin Production
Authors: Mellor Glen E. , Fegan Narelle , Gobius Kari S. , Smith Helen V. , Jennison Amy V. , D'Astek Beatriz A. , Rivas Marta , Shringi Smriti , Baker Katherine N. K. , Besser Thomas E.
Published: December 2014

While the differential association of
Escherichia coli
O157 genotypes with animal and human hosts has recently been well documented, little is known about their distribution between countries and how this might affect regional disease rates. Here, we used a 48-plex single nucleotide polymorphism (SNP) assay to segregate 148
E. coli
O157 isolates from Australia, Argentina, and the United States into 11 SNP lineages. We also investigated the relationship between SNP lineages, Shiga toxin (Stx) gene profiles, and total Stx production.
E. coli
O157 isolates clearly segregated into SNP lineages that were differentially associated with each country. Of the 11 SNP lineages, seven were detected among isolates from a single country, two were detected among isolates from all three countries, and another two were detected only among U.S. and Argentinean isolates. A number of Australian (30%) and Argentinean (14%) isolates were associated with novel, previously undescribed SNP lineages that were unique to each country. Isolates within SNP lineages that were strongly associated with the carriage of
stx
2a
produced comparatively more Stx on average than did those lacking the
stx
2a
subtype. Furthermore, the proportion of isolates in
stx
2a
-associated SNP lineages was significantly higher in Argentina and the United States than Australia (
P
< 0.05). This study provides evidence for the geographic divergence of
E. coli
O157 and for a prominent role of
stx
2a
in total Stx production. These results also highlight the need for more comprehensive studies of the global distribution of
E. coli
O157 lineages and the impacts of regionally predominant
E. coli
O157 lineages on the prevalence and severity of disease.
Improved Detection of Staphylococcus intermedius Group in a Routine Diagnostic Laboratory
Authors: Lee John , Murray Aimee , Bendall Richard , Gaze William , Zhang Lihong , Vos Michiel
Published: December 2014

The
Staphylococcus intermedius
group (SIG) includes zoonotic pathogens traditionally associated with dog bites. We describe a simple scheme for improved detection of SIG using routine laboratory methods, report its effect on isolation rates, and use sequencing to confirm that, apart from one atypical SIG strain, most isolates are
Staphylococcus pseudintermedius
.
Equal Performance of Self-Collected and Health Care Worker-Collected Pharyngeal Swabs for Group A Streptococcus Testing by PCR
Authors: Murray Martha A. , Schulz Lorie A. , Furst Joseph W. , Homme Jason H. , Jenkins Sarah M. , Uhl James R. , Patel Robin , Cockerill Franklin C. , Myers Jane F. , Pritt Bobbi S.
Published: December 2014

A process employing patient- or parent-collected pharyngeal swabs for group A
Streptococcus
(GAS) testing would expedite diagnosis and treatment, reduce patient exposure to the health care setting, and decrease health care costs. Our aim was to determine the concordance between patient- or parent-collected (self-collected) and health care worker (HCW)-collected pharyngeal swabs for detection of GAS by PCR. From 9 October 2012 to 21 March 2013, patients presenting with a sore throat meeting criteria for GAS testing and not meeting criteria for severe disease were offered the opportunity to collect their own pharyngeal swab. The HCW also collected a swab. Paired swabs were tested by GAS real-time PCR, allowing semiquantitative comparisons between positive results. Of the 402 participants, 206 had a swab collected by the patient and 196 a swab collected by the parent. The percent positivity results were 33.3% for HCW-collected swabs and 34.3% for self-collected swabs (
P
= 0.41). The overall concordance between the two collection strategies was 94.0% (95% confidence interval [CI], 91.3 to 96.0). Twenty-four of the paired swabs had discordant results, with 10 and 14 positives detected only with the HCW- and self-collected swabs, respectively (
P
= 0.41). The person collecting the swab in the self-collected arm, the order of collection, and prior swab collection training did not influence results. Among the 124 specimens that were positive by both collection methods, the amount of GAS DNA was higher in the self-collected versus the HCW-collected swabs (
P
= 0.008). Self-collected pharyngeal swabs provide a reliable alternative to HCW collection for detection of GAS and offer a strategy for improved health care delivery.
Nonstructural Protein 1-Specific Immunoglobulin M and G Antibody Capture Enzyme-Linked Immunosorbent Assays in Diagnosis of Flaviviral Infections in Humans
Authors: Chao Day-Yu , Galula Jedhan Ucat , Shen Wen-Fan , Davis Brent S. , Chang Gwong-Jen J.
Published: December 2014

IgM antibody- and IgG antibody-capture enzyme-linked immunosorbent assays (MAC/GAC-ELISAs) targeted at envelope protein (E) of dengue viruses (DENV), West Nile virus, and Japanese encephalitis virus (JEV) are widely used as serodiagnostic tests for presumptive confirmation of viral infection. Antibodies directed against the flavivirus nonstructural protein 1 (NS1) have been proposed as serological markers of natural infections among vaccinated populations. The aim of the current study is to optimize an IgM and IgG antibody-capture ELISA (MAC/GAC-ELISA) to detect anti-NS1 antibodies and compare it with anti-E MAC/GAC-ELISA. Plasmids to express premembrane/envelope (prM/E) or NS1 proteins of six medically important flaviviruses, including dengue viruses (DENV-1 to DENV-4), West Nile virus (WNV), and Japanese encephalitis virus (JEV), were constructed. These plasmids were used for the production of prM/E-containing virus-like particles (VLPs) and secreted NS1 (sNS1) from COS-1 cells. Archived clinical specimens from patients with confirmed DENV, JEV, and WNV infections, along with naive sera, were subjected to NS1-MAC/GAC-ELISAs before or after depletion of anti-prM/E antibodies by preabsorption with or without VLPs. Human serum specimens from previously confirmed DENV infections showed significantly enhanced positive-to-negative (P/N) ratios for NS1-MAC/GAC-ELISAs after the depletion of anti-prM/E antibodies. No statistical differences in sensitivities and specificities were found between the newly developed NS1- and VLP-MAC/GAC-ELISAs. Further application of the assays to WNV- and JEV-infected serum panels showed similar results. A novel approach to perform MAC/GAC-ELISAs for NS1 antibody detection was successfully developed with great potential to differentiate antibodies elicited by the tetravalent chimeric yellow fever-17D/dengue vaccine or DENV infection.
First Report of an Infant Botulism Case Due to Clostridium botulinum Type Af
Authors: de Jong Laura I. T. , Fernández Rafael A. , Pareja Virtudes , Giaroli Gabriel , Guidarelli Sergio R. , Dykes Janet K. , Lúquez Carolina
Published: December 2014

Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely,
Clostridium botulinum
strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to
C. botulinum
type Af worldwide.
Identification and Susceptibility of Aspergillus Section Nigri in China: Prevalence of Species and Paradoxical Growth in Response to Echinocandins
Authors: Li Yali , Wan Zhe , Liu Wei , Li Ruoyu
Published: December 2014

Molecular identification and
in vitro
antifungal susceptibility tests of 43
Aspergillus
section
Nigri
isolates from China were performed.
Aspergillus niger
and
Aspergillus tubingensis
were present in almost equal numbers. All of the isolates had low MIC/MECs (minimum effective concentrations) for the 7 common antifungals, and a paradoxical effect was observed for the first time in response to caspofungin and micafungin.
The Nucleoprotein of Newly Emerged H7N9 Influenza A Virus Harbors a Unique Motif Conferring Resistance to Antiviral Human MxA
Authors: Riegger David , Hai Rong , Dornfeld Dominik , Mänz Benjamin , Leyva-Grado Victor , Sánchez-Aparicio Maria T , Albrecht Randy A. , Palese Peter , Haller Otto , Schwemmle Martin , García-Sastre Adolfo , Kochs Georg , Schmolke Mirco
Published: December 2014

Interferon-induced Mx proteins show strong antiviral activity against influenza A viruses (IAVs). We recently demonstrated that the viral nucleoprotein (NP) determines resistance of seasonal and pandemic human influenza viruses to Mx, while avian isolates retain Mx sensitivity. We identified a surface-exposed cluster of amino acids in NP of pandemic A/BM/1/1918 (H1N1), comprising isoleucine-100, proline-283, and tyrosine-313, that is essential for reduced Mx sensitivity in cell culture and
in vivo
. This cluster has been maintained in all descendant seasonal strains, including A/PR/8/34 (PR/8). Accordingly, two substitutions in the NP of PR/8 [PR/8(mut)] to the Mx-sensitive amino acids (P283L and Y313F) led to attenuation in Mx1-positive mice. Serial lung passages of PR/8(mut) in Mx1 mice resulted in a single exchange of tyrosine to asparagine at position 52 in NP (in close proximity to the amino acid cluster at positions 100, 283, and 313), which partially compensates loss of Mx resistance in PR/8(mut). Intriguingly, the NP of the newly emerged avian-origin H7N9 virus also contains an asparagine at position 52 and shows reduced Mx sensitivity. N52Y substitution in NP results in increased sensitivity of the H7N9 virus to human Mx, indicating that this residue is a determinant of Mx resistance in mammals. Our data strengthen the hypothesis that the human Mx protein represents a potent barrier against zoonotic transmission of avian influenza viruses. However, the H7N9 viruses overcome this restriction by harboring an NP that is less sensitive to Mx-mediated host defense. This might contribute to zoonotic transmission of H7N9 and to the severe to fatal outcome of H7N9 infections in humans.

IMPORTANCE
The natural host of influenza A viruses (IAVs) are aquatic birds. Occasionally, these viruses cross the species barrier, as in early 2013 when an avian H7N9 virus infected humans in China. Since then, multiple transmissions of H7N9 viruses to humans have occurred, leaving experts puzzled about molecular causes for such efficient crossing of the species barrier compared to other avian influenza viruses. Mx proteins are known restriction factors preventing influenza virus replication. Unfortunately, some viruses (e.g., human IAV) have developed some resistance, which is associated with specific amino acids in their nucleoproteins, the target of Mx function. Here, we demonstrate that the novel H7N9 bird IAV already carries a nucleoprotein that overcomes the inhibition of viral replication by human MxA. This is the first example of an avian IAV that is naturally less sensitive to Mx-mediated inhibition and might explain why H7N9 viruses transmitted efficiently to humans.
MCL1 Enhances the Survival of CD8
+
Memory T Cells after Viral Infection
Authors: Gui Jingang , Hu Zhuting , Tsai Ching-Yi , Ma Tian , Song Yan , Morales Amanda , Huang Li-Hao , Dmitrovsky Ethan , Craig Ruth W. , Usherwood Edward J.
Published: December 2014

Viral infection results in the generation of massive numbers of activated effector CD8
+
T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human
MCL1
as a transgene exhibited a skewing in the proportion of CD8
+
T cells, away from SLECs toward MPECs, during the acute phase of vaccinia virus infection. A higher frequency and total number of antigen-specific CD8
+
T cells were observed in
MCL1
transgenic mice. These findings show that MCL1 can shape the makeup of the CD8
+
T cell response, promoting the formation of long-term memory.

IMPORTANCE
During an immune response to a virus, CD8
+
T cells kill cells infected by the virus, and most die when the infection resolves. However, a small proportion of cells survives and differentiates into long-lived memory cells that confer protection from reinfection by the same virus. This report shows that transgenic expression of an MCL1 protein enhances survival of memory CD8
+
T cells following infection with vaccinia virus. This is important because it shows that MCL1 expression may be an important determinant of the formation of long-term CD8
+
T cell memory.
Virion-Independent Transfer of Replication-Competent Hepatitis C Virus RNA between Permissive Cells
Authors: Longatti Andrea , Boyd Bryan , Chisari Francis V.
Published: December 2014

In this study, we show that replication-competent subgenomic hepatitis C virus (HCV) RNA can be transferred to permissive Huh7 cells, leading to the establishment of viral RNA replication. Further, we show that these events are mediated by exosomes rather than infectious virus particles. If similar events occur
in vivo
, this could represent a novel, albeit inefficient, mechanism of viral spread and immune escape.
Analysis of the Early Immune Response to Infection by Infectious Bursal Disease Virus in Chickens Differing in Their Resistance to the Disease
Authors: Smith Jacqueline , Sadeyen Jean-Remy , Butter Colin , Kaiser Pete , Burt David W.
Published: December 2014

Chicken whole-genome gene expression arrays were used to analyze the host response to infection by infectious bursal disease virus (IBDV). Spleen and bursal tissue were examined from control and infected birds at 2, 3, and 4 days postinfection from two lines that differ in their resistance to IBDV infection. The host response was evaluated over this period, and differences between susceptible and resistant chicken lines were examined. Antiviral genes, including
IFNA
,
IFNG
,
MX1
,
IFITM1
,
IFITM3
, and
IFITM5
, were upregulated in response to infection. Evaluation of this gene expression data allowed us to predict several genes as candidates for involvement in resistance to IBDV.

IMPORTANCE
Infectious bursal disease (IBD) is of economic importance to the poultry industry and thus is also important for food security. Vaccines are available, but field strains of the virus are of increasing virulence. There is thus an urgent need to explore new control solutions, one of which would be to breed birds with greater resistance to IBD. This goal is perhaps uniquely achievable with poultry, of all farm animal species, since the genetics of 85% of the 60 billion chickens produced worldwide each year is under the control of essentially two breeding companies. In a comprehensive study, we attempt here to identify global transcriptomic differences in the target organ of the virus between chicken lines that differ in resistance and to predict candidate resistance genes.
Epstein-Barr Virus Type 2 Latently Infects T Cells, Inducing an Atypical Activation Characterized by Expression of Lymphotactic Cytokines
Authors: Coleman Carrie B. , Wohlford Eric M. , Smith Nicholas A. , King Christine A. , Ritchie Julie A. , Baresel Paul C. , Kimura Hiroshi , Rochford Rosemary
Published: December 2014

Epstein-Barr virus (EBV) is a well-established B-cell-tropic virus associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV is associated with a number of T-cell lymphomas; however,in vitrostudies utilizing prototypical EBV type 1 (EBV-1) laboratory strains have generally failed to readily infect mature T cells in culture. The difficulties in performingin vitroT-cell experiments have left questions regarding the role of EBV in the pathogenesis of EBV-positive T-cell lymphoproliferative diseases largely unresolved. We report here that the EBV type 2 (EBV-2) strain displays a unique cell tropism for T cells. In remarkable contrast to EBV-1, EBV-2 readily infects primary T cellsin vitro, demonstrating a propensity for CD8+T cells. EBV-2 infection of purified T cells results in expression of latency genes and ultimately leads to T-cell activation, substantial proliferation, and profound alteration of cytokine expression. The pattern of cytokine production is strikingly skewed toward chemokines with roles in lymphocyte migration, demonstrating that EBV-2 has the ability to modulate normal T-cell processes. Collectively, these novel findings identify a previously unknown cell population potentially utilized by EBV-2 to establish latency and lay the foundation for further studies to elucidate the role of EBV in the pathogenesis of T-cell lymphoproliferative diseases.

IMPORTANCEThe ability of EBV to infect T cells is made apparent by its association with a variety of T-cell lymphoproliferative disorders. However, studies to elucidate the pathogenic role of EBV in these diseases have been limited by the inability to conductin vitroT-cell infection experiments. Here, we report that EBV-2 isolates, compromised in the capacity to immortalize B cells, infect CD3+T cellsex vivoand propose a working model of EBV-2 persistence where alteration of T-cell functions resulting from EBV-2 infection enhances the establishment of latency in B cells. If indeed EBV-2 utilizes T cells to establish a persistent infection, this could provide one mechanism for the association of EBV with T-cell lymphomas. The novel finding that EBV-2 infects T cells in culture will provide a model to understand the role EBV plays in the development of T-cell lymphomas.
Herpes Simplex Virus 1 gN Partners with gM To Modulate the Viral Fusion Machinery
Authors: El Kasmi Imane , Lippé Roger
Published: December 2014

Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus, where they incorporate the viral genome. They then transit through the two nuclear membranes and are wrapped by a host-derived envelope. In the process, several HSV-1 proteins are targeted to the nuclear membranes, but their roles in viral nuclear egress are unclear. Among them, glycoprotein M (gM), a known modulator of virus-induced membrane fusion, is distributed on both the inner and outer nuclear membranes at the early stages of the infection, when no other viral glycoproteins are yet present there. Later on, it is found on perinuclear virions and ultimately redirected to the trans-Golgi network (TGN), where it cycles with the cell surface. In contrast, transfected gM is found only at the TGN and cell surface, hinting at an interaction with other viral proteins. Interestingly, many herpesvirus gM analogs interact with their gN counterparts, which typically alters their intracellular localization. To better understand how HSV-1 gM localization is regulated, we evaluated its ability to bind gN and discovered it does so in both transfected and infected cells, an interaction strongly weakened by the deletion of the gM amino terminus. Functionally, while gN had no impact on gM localization, gM redirected gN from the endoplasmic reticulum (ER) to the TGN. Most interestingly, gN overexpression stimulated the formation of syncytia in the context of an infection by a nonsyncytial strain, indicating that gM and gN not only physically but also functionally interact and that gN modulates gM's activity on membrane fusion.

IMPORTANCE
HSV-1 gM is an important modulator of virally induced cell-cell fusion and viral entry, a process that is likely finely modulated in time and space. Until now, little was known of the proteins that regulate gM's activity. In parallel, gM is found in various intracellular locations at different moments, ranging from nuclear membranes, perinuclear virions, the TGN, cell surface, and mature extracellular virions. In transfected cells, however, it is found only on the TGN and cell surface, hinting that its localization is modulated by other viral proteins. The present study identifies HSV-1 gN as a binding partner for gM, in agreement with their analogs in other herpesviruses, but most excitingly shows that gN modulates gM's impact on HSV-1-induced membrane fusion. These findings open up new research avenues on the viral fusion machinery.
Opposite trends in the consumption of manufactured and roll-your-own cigarettes in Spain (1991–2020)
Authors: Fu Marcela , Martínez-Sánchez Jose M , Clèries Ramon , Villalbí Joan R , Daynard Richard A , Connolly Gregory N , Fernández Esteve
Published: December 2014

Objective

The aim of this study is to describe trends in the consumption of manufactured and roll-your-own cigarettes between 1991 and 2012 in Spain, and to project these trends up to 2020.

Methods

We estimated daily consumption per capita during 1991–2012 using data on sales of manufactured cigarettes (20-packs) and rolling tobacco (kg) from the Tobacco Market Commission, and using data of the Spanish adult population from the National Statistics Institute. We considered different weights (0.5, 0.8 and 1 g) to compute the number of rolled cigarettes per capita. We computed the annual per cent of change and assessed possible changes in trends using joinpoint regression, and projected the consumption up to 2020 using Bayesian methods.

Results

Daily consumption per capita of manufactured cigarettes decreased on average by 3.0% per year in 1991–2012, from 7.6 to 3.8 units, with three trend changes. However, daily consumption per capita of roll-your-own cigarettes increased on average by 14.1% per year, from 0.07 to 0.92 units of 0.5 g, with unchanged trends. Together, daily consumption per capita decreased between 2.9% and 2.5%, depending on the weight of the roll-your-own cigarettes. Projections up to 2020 indicate a decrease of manufactured cigarettes (1.75 units per capita) but an increase of roll-your-own cigarettes (1.25 units per capita).

Conclusions

While the consumption per capita of manufactured cigarettes has decreased in the past years in Spain, the consumption of roll-your-own cigarettes has increased at an annual rate around 14% over the past years. Whereas a net decrease in cigarette consumption is expected in the future, use of roll-your-own cigarettes will continue to increase.
A clinico-ethical framework for multidisciplinary review of medication in nursing homes
Authors: Baqir Wasim , Barrett Steven , Desai Nisha , Copeland Richard , Hughes Julian
Published: December 2014

Residents in care homes are more likely to be prescribed multiple medicines yet often have little involvement in these prescribing decisions. Reviewing and stopping inappropriate medicines is not currently adopted across the health economy. This Health Foundation funded Shine project developed a pragmatic approach to optimising medicines in care homes while involving all residents in decision making.

The pharmacist undertook a detailed medication review using primary care records. The results were discussed at a multidisciplinary team (MDT) meeting involving the care home nurse and the resident’s general practitioner (GP), with input from the local psychiatry of old age service (POAS) where appropriate.

Suggestions for medicines which should be stopped, changed or started, and other interventions (eg monitoring) were discussed with the resident and/or their family.

Over 12 months 422 residents were reviewed, and 1346 interventions were made in 91% of residents reviewed with 15 different types of interventions. The most common intervention (52.3%) was to stop medicines; 704 medicines stopped in 298 residents (70.6%). On average, 1.7 medicines were stopped for every resident reviewed (range zero to nine medicines; SD=1.7), with a 17.4% reduction in medicines prescribed (3602 medicines prescribed before and 2975 after review). The main reasons for stopping medicines were: no current indication (401 medicines; 57%), resident not wanting medicine after risks and benefits were explained (120 medicines; 17%), and safety concerns (42 medicines; 6%).

The net annualised savings against the medicines budget were £77,703 or £184 per person reviewed. The cost of delivering the intervention was £32,670 (pharmacist, GP, POAS consultant, and care home nurse time) for 422 residents; for every £1 invested, £2.38 could be released from the medicines budget.

This project demonstrated that a multidisciplinary medication review with a pharmacist, doctor, and care home nurse can safely reduce inappropriate medication in elderly care home residents.
Improving acute eye consultations in general practice: a practical approach
Authors: Teo Michelle Ai Ling
Published: December 2014

There is significant evidence that patients with acute eye symptoms are poorly assessed in primary care. There is a tendency to diagnose viral or bacterial conjunctivitis in any acutely red eye. This has led to delays in treatment and in some cases, permanent loss of sight.

The aim of this project was to improve acute eye consultations within the Birchwood Medical Practice. The project focused on the "red flag" findings that would identify patients who require referral for same-day ophthalmology assessment.

A retrospective baseline audit was carried out on all cases read-coded "conjunctivitis" over the period of one year. Initially, only 2.8% of consultations had documented all four findings.

By considering the main factors that lead to poor eye assessments, two main areas for improvement were identified. These were education (reinforced with memory aids) and improving the availability of eye examination equipment within each consultation room. An "eye examination kit" was developed with the needs of the general practitioner in mind.

The practice was re-audited six weeks following the intervention. Consultations where all four red flag findings were documented rose from 2.8% to 50%. This was found to be a statistically significant difference (p < 0.01). Pain was checked 63% of the time, compared to 26% prior to intervention. Visual acuity screening had increased to from 35% to 69%. Photophobia was the most significantly increased metric, from being documented only 6% of the time to now 63% of the time. Documentation of whether the symptoms were unilateral or bilateral had also increased from 88% to 94% of consultations.

The initial audit indicated that general practitioners often diagnosed conjunctivitis without screening for symptoms of sight-threatening disease. However, it was clear from the results that the doctors had made a significant change to their approach to acute eye consultations. This shows that doctors are willing to make changes to their behaviour when given the right tools and information. It was felt that a first-hand understanding of the problem and an open discussion regarding the changes required was key to the success of this project.

This project has shown that significant improvements can be achieved with practical and inexpensive interventions. Therefore, general practices throughout the UK are encouraged to adopt similar strategies to improve the identification of patients needing same-day Ophthalmology assessment.
Trends in the incidence and prevalence of cardiac pacemaker insertions in an ageing population
Authors: Bradshaw Pamela J , Stobie Paul , Knuiman Matthew W , Briffa Thomas G , Hobbs Michael S T
Published: December 2014

Objectives

To determine contemporary population estimates of the prevalence of cardiac permanent pacemaker (PPM) insertions.

Methods

A population-based observational study using linked hospital morbidity and death registry data from Western Australia (WA) to identify all incident cases of PPM insertion for adults aged 18 years or older. Prevalence rates were calculated by age and sex for the years 1995–2009 for the WA population.

Results

There were 9782 PPMs inserted during 1995–2009. Prevalence rose across the study period, exceeding 1 in 50 among people aged 75 or older from 2005. This was underpinned by incidence rates which rose with age, being highest in those 85 years or older; over 500/100 000 for men throughout, and over 200/100 000 for women. Rates for patients over 75 were more than double the rates for those aged 65–74 years. Women were around 40% of cases overall. The use of dual-chamber and triple-chamber pacing increased across the study period. A cardiac resynchronisation defibrillator was implanted for 58% of patients treated with cardiac resynchronisation therapy.

Conclusions

Rates of insertion and prevalence of PPM continue to rise with the ageing population in WA. As equilibrium has probably not been reached, the demand for pacing services in similarly well-developed economies is likely to continue to grow.
Grape seed proanthocyanidins ameliorates cadmium-induced renal injury and oxidative stress in experimental rats through the up-regulation of nuclear related factor 2 and antioxidant responsive elements
Authors: Nazima Bashir , Manoharan Vaihundam , Miltonprabu Selvaraj
Published: December 2014

Cadmium (Cd) preferentially accumulates in the kidney, the major target for Cd-related toxicity. Cd-induced reactive oxygen species (ROS) have been considered crucial mediators for renal injury. The biologically significant ionic form of cadmium (Cd+) binds to many bio-molecules, and these interactions underlie the toxicity mechanisms of Cd. The present study was hypothesized to explore the protective effect of grape seed proanthocyanidins (GSP) on Cd-induced renal toxicity and to elucidate the potential mechanism. Male Wistar rats were treated with Cd as cadmium chloride (CdCl2, 5 mg·kg−1bw, orally) and orally pre-administered with GSP (100 mg·kg−1bw) 90 min before Cd intoxication for 4 weeks to evaluate renal damage of Cd and antioxidant potential of GSP. Serum renal function parameters (blood urea nitrogen and creatinine) levels in serum and urine, renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic, and non-enzymatic antioxidants), inflammatory (NF-κB p65, NO, TNF-α, IL-6), apoptotic (caspase-3, caspase-9, Bax, Bcl-2), membrane bound ATPases, and Nrf2 (HO-1, keap1, γ-GCS, and μ-GST) markers were evaluated in Cd-treated rats. Pretreatment with GSP revealed a significant improvement in renal oxidative stress markers in kidneys of Cd-treated rats. In addition, GSP treatment decreases the amount of iNOS, NF-κB, TNF-α, caspase-3, and Bax and increases the levels Bcl-2 protein expression. Similarly, mRNA and protein analyses substantiated that GSP treatment notably normalizes the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in the Cd-treated rats. Histopathological and ultra-structural observations also demonstrated that GSP effectively protects the kidney from Cd-induced oxidative damage. These findings suggest that GSP ameliorates renal dysfunction and oxidative stress through the activation of Nrf2 pathway in Cd-intoxicated rats.
Effect of solute–solvent interactions on DPPH radical scavenging efficiency of some flavonoid antioxidants in various binary water–methanol mixtures
Authors: Jabbari Morteza , Moallem Hamid Reza
Published: December 2014

Scavenging ability of three kinds of natural flavonoid antioxidants including chrysin, naringenin, and quercetin against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical was evaluated by the UV-vis spectrophotometric technique in different aqueous mixtures of methanol (50%–90% v/v) at physiological pH. The studied flavonoids showed their activity to be comparable with ascorbic acid (vitamin C), which is used as a standard reference material in most testing methods. Our findings indicated that an increase in the organic solvent percentage (v/v) has different effects on the radical scavenging efficiency of flavonoids presumably due to solute–solvent interactions. These variations were analyzed in light of various simple and multiple regression equations using the normalized polarity parameter ([Formula: see text]) and Kamlet, Abboud, and Taft solvatochromic parameters. Moreover, The IC50 values of the samples were then obtained by the Yasuda–Shedlovsky extrapolation procedure in pure water.
Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway smooth muscle and epithelial cells
Authors: Keenan Christine R. , Schuliga Michael J. , Stewart Alastair G.
Published: December 2014

The long noncoding RNA (lncRNA) GAS5 has been found to act as a decoy for the glucocorticoid receptor (GR), thus implicating GAS5 as a potential regulator of glucocorticoid sensitivity and resistance. Airway smooth muscle (ASM) cells and airway epithelial cells (AEC) play an important role in the pathogenesis and persistence of asthma and other chronic airways diseases. These airway structural cell types are also important cellular targets of the anti-inflammatory actions of glucocorticoids. In this study, we sought to examine the relevance of GAS5 to glucocorticoid sensitivity and resistance in ASM and AEC. We provide the first evidence that pro-inflammatory mediators up-regulate GAS5 levels in both airway epithelial and smooth muscle cells, and that decreasing GAS5 levels can enhance glucocorticoid action in AEC.
High-resolution demultiplexers based on coupled-resonator effect in cross plasmonic-waveguide structure
Authors: Ye Qihui , Wang Chen , Guo Kai , Chen Wenzhi
Published: December 2014

An ultracompact wavelength demultiplexing structure based on the resonator-coupled effect is proposed and demonstrated numerically. The structure consists of a cross plasmonic-waveguide structure with baffles in the output channels, each of which functions as resonator. Due to the strong couplings of different resonators in the structure, a series of continuous sharp transmission spectra occur. This considerably increases the wavelength resolution of wavelength demultiplexing, which is obviously narrower than the full width of the isolated resonator. The proposed structure could be utilized to design of ultracompact wavelength-division multiplexing (WDM) systems for large-scale photonic integration.
Ordered Field Property for Semi-Markov Games when One Player Controls Transition Probabilities and Transition Times
Authors: Mondal Prasenjit , Sinha Sagnik
Published: December 2014

Two-person finite semi-Markov games (SMGs) are studied when the transition probabilities and the transition times are controlled by one player at all states. For the discounted games in this class, we prove that the ordered field property holds and there exist optimal/Nash equilibrium stationary strategies for the players. We illustrate that the zero-sum SMGs where only transition probabilities are controlled by one player, do not necessarily satisfy the ordered field property. An algorithm along with a numerical example for the discounted one player control zero-sum SMGs is given via linear programming. For the undiscounted version of such games, we exhibit with an example that if the game ceases to be unichain, an optimal stationary or Markov strategy need not exist, (though in this example of a one-player game we exhibit a semi-stationary optimal strategy/policy). Lastly, we prove that if such games are unichain, then they possess the ordered field property for the undiscounted case as well.
Covariant diagonalization of the perfect fluid stress–energy tensor
Authors: Garat Alcides
Published: December 2014

We introduce new tetrads that manifestly and covariantly diagonalize the stress–energy tensor for a perfect fluid with vorticity at every spacetime point. This new tetrad can be applied to introduce simplification in the analysis of astrophysical relativistic problems where vorticity is present through the Carter–Lichnerowicz equation. We also discuss the origin of inertia in this special case from the standpoint of our new local tetrads.
Design and Comparative Analysis of High Performance Carbon Nanotube-Based Operational Transconductance Amplifiers
Authors: Loan Sajad A. , Nizamuddin M. , Alamoud Abdul R. , Abbasi Shuja A.
Published: December 2014

In this paper, novel carbon nanotube (CNT) based operational transconductance amplifiers (OTAs) have been designed and simulated. Three types of CNT-based OTAs have been designed at 45 nm technology node and have been compared with the conventional CMOS-based OTA. The comparative analysis of the key characteristics of all the devices has revealed that a significant improvement in performance is observed in the CNT-based OTAs, particularly in a pure CNT-OTA. In the pure CNT-OTA, DC gain has increased by 218%, slew rate has increased by 22.58%, the output resistance has increased by 55.2% and the power consumption is ∼ 193 times less in comparison to the conventional CMOS-OTA. Further, common mode rejection ratio (CMRR) and power supply rejection ratio positive (PSRR+) has increased by 31.87% and 136.3%, respectively in pure CNT-OTA. The performance of CNT-based OTAs has also been studied thoroughly by varying the number of CNTs (N), CNT pitch (S) and the diameter of CNTs (D CNT ) at 0.9 V. It has been observed that their performance can be improved further by using optimized values of CNT number; inter CNT-pitch and diameter. The stability analysis has shown that the pure CNT-OTA is highly stable. A 16.7% and 4% increase in phase and gain margins is achieved in the pure CNT-OTA in comparison to the bulk CMOS OTA. Finally, band and high pass filters have been realized by using the proposed CNT-based OTAs.
The development of the Betton Farm Coral Bed within the Malton Oolite Member (Upper Jurassic, Middle Oxfordian) of the Scarborough District, North Yorkshire, UK
Authors: Wright John K. , Rawson Peter F.
Published: December 2014

Betton Farm quarries contain, within a small area, a remarkable range of facies associated with the development of a Jurassic coral reef. A NW–SE-trending barrier reef protected the whole area containing the two quarries. Betton Farm North Quarry displays
Thamnasteria
patch reefs. These consist of scattered, 1 m high masses of colonial coral surrounded by reef debris that were situated behind the barrier within a large reef platform area. In Betton Farm South Quarry, bioclastic sand, consisting largely of coral and bivalve debris, interdigitates with the development of a small ribbon reef made up of the massive colonial coral
Thamnasteria
. This ribbon reef, only 3 to 4 m wide, sheltered a lagoonal area that accumulated lime mud and was colonized by large gastropods and burrowing bivalves. A fauna of reef-specializing bivalves and echinoids occupied these areas of patch/ribbon reef development, which were periodically swept by nutrient-bearing currents. Competition between the growth of the ribbon of
Thamnasteria
and the accumulation of fringing sediments saw periods when the
Thamnasteria
expanded over the coral-shell sand, and periods when the encroaching sediment cut back the growth of the
Thamnasteria
considerably. Considered initially to represent the Coral Rag Member of the Coralline Oolite Formation, the Betton Farm Coral Bed is now seen to represent localized coral reef developments situated near the base of the Malton Oolite Member, and growing upon antecedent bedrock features such as hard-ground surfaces that formed during pauses in sedimentation of the Malton Oolite.
Echinoid remains preserved in a Derbyshire screwstone (Mississippian, Visean, Brigantian), UK
Authors: Donovan Stephen K. , Lewis David N. , Bouman Roderick W.
Published: December 2014

Fossil echinoids are moderately common in the Mississippian (Lower Carboniferous) limestones of the White Peak of Derbyshire and Staffordshire, but are invariably disarticulated; in consequence, they have received little attention. Herein, we record echinoid radioles (spines) from the chert of a Derbyshire screwstone for the first time. These specimens come from the Monsal Dale Limestone Formation (Brigantian, Visean) of Bradford Dale, near Youlgrave, Derbyshire. Radioles are slender, smooth, rounded in section, straight to slightly curved, but incomplete. We refer these specimens to
Lepidocidaris
sp., a genus previously recorded from the Preston area of Lancashire and Iowa, USA. The radioles are accumulated in a near-linear bedding plane assemblage, indicating a unidirectional current flow at the time of deposition.