bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome analyses resolve early branches in the tree of life of modern birds
Authors: Jarvis Erich D. , Mirarab Siavash , Aberer Andre J. , Li Bo , Houde Peter , Li Cai , Ho Simon Y. W. , Faircloth Brant C. , Nabholz Benoit , Howard Jason T. , Suh Alexander , Weber Claudia C. , da Fonseca Rute R. , Li Jianwen , Zhang Fang , Li Hui , Zhou Long , Narula Nitish , Liu Liang , Ganapathy Ganesh , Boussau Bastien , Bayzid Md. Shamsuzzoha , Zavidovych Volodymyr , Subramanian Sankar , Gabaldón Toni , Capella-Gutiérrez Salvador , Huerta-Cepas Jaime , Rekepalli Bhanu , Munch Kasper , Schierup Mikkel , Lindow Bent , Warren Wesley C. , Ray David , Green Richard E. , Bruford Michael W. , Zhan Xiangjiang , Dixon Andrew , Li Shengbin , Li Ning , Huang Yinhua , Derryberry Elizabeth P. , Bertelsen Mads Frost , Sheldon Frederick H. , Brumfield Robb T. , Mello Claudio V. , Lovell Peter V. , Wirthlin Morgan , Schneider Maria Paula Cruz , Prosdocimi Francisco , Samaniego José Alfredo , Velazquez Amhed Missael Vargas , Alfaro-Núñez Alonzo , Campos Paula F. , Petersen Bent , Sicheritz-Ponten Thomas , Pas An , Bailey Tom , Scofield Paul , Bunce Michael , Lambert David M. , Zhou Qi , Perelman Polina , Driskell Amy C. , Shapiro Beth , Xiong Zijun , Zeng Yongli , Liu Shiping , Li Zhenyu , Liu Binghang , Wu Kui , Xiao Jin , Yinqi Xiong , Zheng Qiuemei , Zhang Yong , Yang Huanming , Wang Jian , Smeds Linnea , Rheindt Frank E. , Braun Michael , Fjeldsa Jon , Orlando Ludovic , Barker F. Keith , Jønsson Knud Andreas , Johnson Warren , Koepfli Klaus-Peter , O’Brien Stephen , Haussler David , Ryder Oliver A. , Rahbek Carsten , Willerslev Eske , Graves Gary R. , Glenn Travis C. , McCormack John , Burt Dave , Ellegren Hans , Alström Per , Edwards Scott V. , Stamatakis Alexandros , Mindell David P. , Cracraft Joel , Braun Edward L. , Warnow Tandy , Jun Wang , Gilbert M. Thomas P. , Zhang Guojie
Published: December 2014

To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
Ultrastable gold substrates for electron cryomicroscopy
Authors: Russo Christopher J. , Passmore Lori A.
Published: December 2014

Despite recent advances, the structures of many proteins cannot be determined by electron cryomicroscopy because the individual proteins move during irradiation. This blurs the images so that they cannot be aligned with each other to calculate a three-dimensional density. Much of this movement stems from instabilities in the carbon substrates used to support frozen samples in the microscope. Here we demonstrate a gold specimen support that nearly eliminates substrate motion during irradiation. This increases the subnanometer image contrast such that α helices of individual proteins are resolved. With this improvement, we determine the structure of apoferritin, a smooth octahedral shell of α-helical subunits that is particularly difficult to solve by electron microscopy. This advance in substrate design will enable the solution of currently intractable protein structures.
From hell on Earth, life's building blocks
Authors: Perkins Sid
Published: December 2014

Simulated meteorite impact forges RNA components.
Expanding the breadth of an HIV-1 vaccine
Authors: Ofek Gilad , Diskin Ron
Published: December 2014

Immunogens are designed to elicit the production of highly coveted broadly neutralizing antibodies that protect against HIV-1

[Also see Report by

McGuire
et al.

]
Mathematical models for emerging disease
Authors: Dobson Andy
Published: December 2014

How can models provide better insights into pathogen emergence and epidemic prediction?
A Diagnostic HIV-1 Tropism System Based on Sequence Relatedness
Authors: Edwards Suzanne , Stucki Heinz , Bader Joëlle , Vidal Vincent , Kaiser Rolf , Battegay Manuel , Klimkait Thomas
Published: December 2014

Key clinical studies for HIV coreceptor antagonists have used the phenotyping-based Trofile test. Meanwhile various simpler-to-do genotypic tests have become available that are compatible with standard laboratory equipment and Web-based interpretation tools. However, these systems typically analyze only the most prominent virus sequence in a specimen. We present a new diagnostic HIV tropism test not needing DNA sequencing. The system, XTrack, uses physical properties of DNA duplexes after hybridization of single-stranded HIV-1envV3 loop probes to the clinical specimen. Resulting “heteroduplexes” possess unique properties driven by sequence relatedness to the reference and resulting in a discrete electrophoretic mobility. A detailed optimization process identified diagnostic probe candidates relating best to a large number of HIV-1 sequences with known tropism. From over 500 V3 sequences representing all main HIV-1 subtypes (Los Alamos database), we obtained a small set of probes to determine the tropism in clinical samples. We found a high concordance with the commercial TrofileES test (84.9%) and the Web-based tool Geno2Pheno (83.0%). Moreover, the new system reveals mixed virus populations, and it was successful on specimens with low virus loads or on provirus from leukocytes. A replicative phenotyping system was used for validation. Our data show that the XTrack test is favorably suitable for routine diagnostics. It detects and dissects mixed virus populations and viral minorities; samples with viral loads (VL) of <200 copies/ml are successfully analyzed. We further expect that the principles of the platform can be adapted also to other sequence-divergent pathogens, such as hepatitis B and C viruses.
Dengue Virus Induces and Requires Glycolysis for Optimal Replication
Authors: Fontaine Krystal A. , Sanchez Erica L. , Camarda Roman , Lagunoff Michael
Published: December 2014

Viruses rely on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. Dengue virus (DENV), a member of theFlaviviridaefamily, is one of the most important arthropod-borne human pathogens worldwide. We analyzed global intracellular metabolic changes associated with DENV infection of primary human cells. Our metabolic profiling data suggested that central carbon metabolism, particularly glycolysis, is strikingly altered during a time course of DENV infection. Glucose consumption is increased during DENV infection and depriving DENV-infected cells of exogenous glucose had a pronounced impact on viral replication. Furthermore, the expression of both glucose transporter 1 and hexokinase 2, the first enzyme of glycolysis, is upregulated in DENV-infected cells. Pharmacologically inhibiting the glycolytic pathway dramatically reduced DENV RNA synthesis and infectious virion production, revealing a requirement for glycolysis during DENV infection. Thus, these experiments suggest that DENV induces the glycolytic pathway to support efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat DENV infection in the future.

IMPORTANCEApproximately 400 million people are infected with dengue virus (DENV) annually, and more than one-third of the global population is at risk of infection. As there are currently no effective vaccines or specific antiviral therapies for DENV, we investigated the impact DENV has on the host cellular metabolome to identify metabolic pathways that are critical for the virus life cycle. We report an essential role for glycolysis during DENV infection. DENV activates the glycolytic pathway, and inhibition of glycolysis significantly blocks infectious DENV production. This study provides further evidence that viral metabolomic analyses can lead to the discovery of novel therapeutic targets to block the replication of medically important human pathogens.
Timing of Galectin-1 Exposure Differentially Modulates Nipah Virus Entry and Syncytium Formation in Endothelial Cells
Authors: Garner Omai B. , Yun Tatyana , Pernet Olivier , Aguilar Hector C. , Park Arnold , Bowden Thomas A. , Freiberg Alexander N. , Lee Benhur , Baum Linda G.
Published: December 2014

Nipah virus (NiV) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. Endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific N-glycans on the NiV envelope fusion glycoprotein (F). NiV-F mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. Galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on NiV-F to reduce endothelial cell fusion, an effect that may reduce pathophysiologic sequelae of NiV infection. However, galectins play multiple roles in regulating host-pathogen interactions; for example, galectins can promote attachment of HIV to T cells and macrophages and attachment of HSV-1 to keratinocytes but can also inhibit influenza entry into airway epithelial cells. Using live Nipah virus, in the present study, we demonstrate that galectin-1 can enhance NiV attachment to and infection of primary human endothelial cells by bridging glycans on the viral envelope to host cell glycoproteins. In order to exhibit an enhancing effect, galectin-1 must be present during the initial phase of virus attachment; in contrast, addition of galectin-1 postinfection results in reduced production of progeny virus and syncytium formation. Thus, galectin-1 can have dual and opposing effects on NiV infection of human endothelial cells. While various roles for galectin family members in microbial-host interactions have been described, we report opposing effects of the same galectin family member on a specific virus, with the timing of exposure during the viral life cycle determining the outcome.

IMPORTANCENipah virus is an emerging pathogen that targets endothelial cells lining blood vessels; the high mortality rate (up to 70%) in Nipah virus infections results from destruction of these cells and resulting catastrophic hemorrhage. Host factors that promote or prevent Nipah virus infection are not well understood. Endogenous human lectins, such as galectin-1, can function as pattern recognition receptors to reduce infection and initiate immune responses; however, lectins can also be exploited by microbes to enhance infection of host cells. We found that galectin-1, which is made by inflamed endothelial cells, can both promote Nipah virus infection of endothelial cells by “bridging” the virus to the cell, as well as reduce production of progeny virus and reduce endothelial cell fusion and damage, depending on timing of galectin-1 exposure. This is the first report of spatiotemporal opposing effects of a host lectin for a virus in one type of host cell.
Structural Analysis of a Rabbit Hemorrhagic Disease Virus Binding to Histo-Blood Group Antigens
Authors: Leuthold Mila M. , Dalton Kevin P. , Hansman Grant S.
Published: December 2014

Rabbit hemorrhagic disease virus (RHDV) is a member of the
Caliciviridae
family (
Lagovirus
genus). RHDV is highly contagious and attaches to epithelial cells in the digestive or respiratory tract, leading to massive lesions with high mortality rates. A new variant of RHDV (termed RHDVb) recently has emerged, and previously vaccinated rabbits appear to have little protection against this new strain. Similar to human norovirus (
Caliciviridae
,
Norovirus
genus), RHDV binds histo-blood group antigens (HBGAs), and this is thought to be important for infection. Here, we report the HBGA binding site on the RHDVb capsid-protruding domain (P domain) using X-ray crystallography. The HBGA binding pocket was located in a negatively charged patch on the side of the P domain and at a dimeric interface. Residues from both monomers contributed to the HBGA binding and involved a network of direct hydrogen bonds and water-mediated interactions. An amino acid sequence alignment of different RHDV strains indicated that the residues directly interacting with the ABH-fucose of the HBGAs (Asp472, Asn474, and Ser479) were highly conserved. This result suggested that different RHDV strains also could bind HBGAs at the equivalent pocket. Moreover, several HBGA binding characteristics between RHDVb and human genogroup II norovirus were similar, which indicated a possible convergent evolution of HBGA binding interactions. Further structural studies with other RHDV strains are needed in order to better understand the HBGA binding mechanisms among the diverse RHDV strains.

IMPORTANCE
We identified, for the first time, the HBGA binding site on an RHDVb P domain using X-ray crystallography. Our results showed that RHDVb and human genogroup II noroviruses had similar HBGA binding interactions. Recently, it was discovered that synthetic HBGAs or HBGA-expressing enteric bacteria could enhance human genogroup II norovirus infection in B cells. Considering that RHDVb and genogroup II norovirus similarly interacted with HBGAs, it may be possible that a comparable cell culture system also could work with RHDVb. Taken together, these new findings will extend our understanding of calicivirus HBGA interactions and may help to elucidate the specific roles of HBGAs in calicivirus infections.
Functional Characterization of Nuclear Trafficking Signals in Pseudorabies Virus pUL31
Authors: Paßvogel Lars , Klupp Barbara G. , Granzow Harald , Fuchs Walter , Mettenleiter Thomas C.
Published: December 2014

The herpesviral nuclear egress complex (NEC), consisting of pUL31 and pUL34 homologs, mediates efficient translocation of newly synthesized capsids from the nucleus to the cytosol. The tail-anchored membrane protein pUL34 is autonomously targeted to the nuclear envelope, while pUL31 is recruited to the inner nuclear membrane (INM) by interaction with pUL34. A nuclear localization signal (NLS) in several pUL31 homologs suggests importin-mediated translocation of the protein. Here we demonstrate that deletion or mutation of the NLS in pseudorabies virus (PrV) pUL31 resulted in exclusively cytosolic localization, indicating active nuclear export. Deletion or mutation of a predicted nuclear export signal (NES) in mutant constructs lacking a functional NLS resulted in diffuse nuclear and cytosolic localization, indicating that both signals are functional. pUL31 molecules lacking the complete NLS or NES were not recruited to the INM by pUL34, while site-specifically mutated proteins formed the NEC and partially complemented the defect of the UL31 deletion mutant. Our data demonstrate that the N terminus of pUL31, encompassing the NLS, is required for efficient nuclear targeting but not for pUL34 interaction, while the C terminus, containing the NES but not necessarily the NES itself, is required for complex formation and efficient budding of viral capsids at the INM. Moreover, pUL31-ΔNLS displayed a dominant negative effect on wild-type PrV replication, probably by diverting pUL34 to cytoplasmic membranes.

IMPORTANCE
The molecular details of nuclear egress of herpesvirus capsids are still enigmatic. Although the key players, homologs of herpes simplex virus pUL34 and pUL31, which interact and form the heterodimeric nuclear egress complex, are well known, the molecular basis of this interaction and the successive budding, vesicle formation, and scission from the INM, as well as capsid release into the cytoplasm, remain largely obscure. Here we show that classical cellular targeting signals for nuclear import and export are important for proper localization and function of the NEC, thus regulating herpesvirus nuclear egress.
The Progressive Adaptation of a Georgian Isolate of African Swine Fever Virus to Vero Cells Leads to a Gradual Attenuation of Virulence in Swine Corresponding to Major Modifications of the Viral Genome
Authors: Krug Peter W. , Holinka Lauren G. , O'Donnell Vivian , Reese Bo , Sanford Brenton , Fernandez-Sainz Ignacio , Gladue Douglas P. , Arzt Jonathan , Rodriguez Luis , Risatti Guillermo R. , Borca Manuel V.
Published: December 2014

African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated
in vitro
for the ability to replicate in Vero cells and primary swine macrophages cultures and
in vivo
for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures.
In vivo
, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed.

IMPORTANCE
The main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been insufficiently described. Details like the numbers of passages required to obtain attenuated viruses, genetic modifications introduced into the virus genomes along passages, and the extent of attenuation and induced protective efficacy are not readily available. In this study, we assessed the changes that lead to decreased growth in swine macrophages and to attenuation in swine. Loss of virulence, probably associated with limited replication
in vivo
, may lead to the lack of protective immunity in swine observed after challenge. This report provides valuable information that can be used to further the understanding of ASFV gene function, virus attenuation, and protection against infection.
N
-Linked Glycosylation Protects Gammaretroviruses against Deamination by APOBEC3 Proteins
Authors: Rosales Gerpe María Carla , Renner Tyler Milston , Bélanger Kasandra , Lam Cindy , Aydin Halil , Langlois Marc-André
Published: December 2014

Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. More specifically, we find that the number of
N
-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor.

IMPORTANCE
APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. These enzymes hinder their replication and intensely mutate their DNA, thereby inactivating viral progeny and the spread of infection. Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically,
N
-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. By carefully controlling the amount of mutations caused by APOBEC3 proteins, gammaretroviruses can find a balance that helps them evolve and persist.
Reducing hospital-acquired infections and improving the rational use of antibiotics in a developing country: an effectiveness study
Authors: Murni Indah K , Duke Trevor , Kinney Sharon , Daley Andrew J , Soenarto Yati
Published: December 2014

Background

Prevention of hospital-acquired infections (HAI) is central to providing safe and high quality healthcare. Transmission of infection between patients by health workers, and the irrational use of antibiotics have been identified as preventable aetiological factors for HAIs. Few studies have addressed this in developing countries.

Aims

To implement a multifaceted infection control and antibiotic stewardship programme and evaluate its effectiveness on HAIs and antibiotic use.

Methods

A before-and-after study was conducted over 27 months in a teaching hospital in Indonesia. All children admitted to the paediatric intensive care unit and paediatric wards were observed daily. Assessment of HAIs was made based on the criteria from the Centers for Disease Control and Prevention. The multifaceted intervention consisted of a hand hygiene campaign, antibiotic stewardship (using the WHO Pocket Book of Hospital Care for Children guidelines as standards of antibiotic prescribing for community-acquired infections), and other elementary infection control practices. Data were collected using an identical method in the preintervention and postintervention periods.

Results

We observed a major reduction in HAIs, from 22.6% (277/1227 patients) in the preintervention period to 8.6% (123/1419 patients) in the postintervention period (relative risk (RR) (95% CI) 0.38 (0.31 to 0.46)). Inappropriate antibiotic use declined from 43% (336 of 780 patients who were prescribed antibiotics) to 20.6% (182 of 882 patients) (RR 0.46 (0.40 to 0.55)). Hand hygiene compliance increased from 18.9% (319/1690) to 62.9% (1125/1789) (RR 3.33 (2.99 to 3.70)). In-hospital mortality decreased from 10.4% (127/1227) to 8% (114/1419) (RR 0.78 (0.61 to 0.97)).

Conclusions

Multifaceted infection control interventions are effective in reducing HAI rates, improving the rational use of antibiotics, increasing hand hygiene compliance, and may reduce mortality in hospitalised children in developing countries.
Medical rota changes and venous thromboembolism prophylaxis in orthopaedic patients
Authors: Bohler Iain , George Mackenzie Jardine Alan
Published: December 2014

Efficacy of clinical guidelines to improve patient care is highly dependent on the ability of hospital teams to interpret and implement advised standards of care. Trimester and bi-annual rotation changes often see transference and loss of acquired experience and knowledge from wards with ensuing shortfalls in patient safety and care quality. Such shortfalls were noticed in the ability of our unit to adhere to national venous thromboembolism (VTE) prophylaxis measures. A prospective quality improvement audit was embarked upon to address this.

An initial audit of VTE prophylaxis in 112 patients demonstrated just 71% compliance with suggested measures. Errors were predominantly medical in origin and secondary to poor understanding, interpretation, and knowledge of VTE guidelines. Errors were also noted in nursing and patient compliance to measures.

Repeated re-auditing demonstrated increased error (following initial improvement post audit) after periods of medical staff rotation. Through education of junior medical and nursing staff, and of patients, the unit was able to achieve 100% compliance.

Rota changes often induce conflict of interest between maintaining adequate services and high levels of patient care or providing suitable and informed induction programmes for new medical staff. Emphasised education of VTE prophylaxis guidelines has now become part of induction of junior medical staff, whilst ward based measures ensure daily compliance. The success of the audit strategy has led to its use throughout other surgical units within the hospital.
Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach
Authors: Su Longxiang , Huang Yingyu , Zhu Ying , Xia Lei , Wang Rentao , Xiao Kun , Wang Huijuan , Yan Peng , Wen Bo , Cao Lichao , Meng Nan , Luan Hemi , Liu Changting , Li Xin , Xie Lixin
Published: December 2014

Background

To identify metabolic biomarkers that can be used to differentiate sepsis from systemic inflammatory response syndrome (SIRS), assess severity and predict outcomes.

Methods

65 patients were involved in this study, including 35 patients with sepsis, 15 patients with SIRS and 15 normal patients. Small metabolites that were present in patient serum samples were measured by liquid chromatography mass spectrometry techniques and analysed using multivariate statistical methods.

Results

The metabolic profiling of normal patients and patients with SIRS or sepsis was markedly different. A significant decrease in the levels of lactitol dehydrate andS-phenyl-d-cysteine and an increase in the levels ofS-(3-methylbutanoyl)-dihydrolipoamide-E andN-nonanoyl glycine were observed in patients with sepsis in comparison to patients with SIRS (p<0.05). Patients with severe sepsis and septic shock displayed lower levels of glyceryl-phosphoryl-ethanolamine, Ne, Ne dimethyllysine, phenylacetamide andd-cysteine (p<0.05) in their sera. The profiles of patients with sepsis 48 h before death illustrated an obvious state of metabolic disorder, such thatS-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol (22:2 (13Z, 16Z)/0:0), glycerophosphocholine andS-succinyl glutathione were significantly decreased (p<0.05). The receiver operating characteristic curve of the differential expression of these metabolites was also performed.

Conclusions

The body produces significant evidence of metabolic disorder during SIRS or sepsis. Seven metabolites may potentially be used to diagnose sepsis.

Trial registration number

ClinicalTrial.gov identifierNCT01649440.
Sequencing of idiopathic pulmonary fibrosis-related genes reveals independent single gene associations
Authors: Coghlan Meghan A , Shifren Adrian , Huang Howard J , Russell Tonya D , Mitra Robi D , Zhang Qunyuan , Wegner Daniel J , Cole F Sessions , Hamvas Aaron
Published: December 2014

Background

Previous studies investigating a genetic basis for idiopathic pulmonary fibrosis (IPF) have focused on resequencing single genes in IPF kindreds or cohorts to determine the genetic contributions to IPF. None has investigated interactions among the candidate genes.

Objective

To compare the frequencies and interactions of mutations in six IPF-associated genes in a cohort of 132 individuals with IPF with those of a disease-control cohort of 192 individuals with chronic obstructive pulmonary disease (COPD) and the population represented in the Exome Variant Server.

Methods

We resequenced the genes encoding surfactant proteins A2 (SFTPA2), and C (SFTPC), the ATP binding cassette member A3 (ABCA3), telomerase (TERT), thyroid transcription factor (NKX2-1) and mucin5B(MUC5B) and compared the collapsed frequencies of rare (minor allele frequency <1%), computationally predicted deleterious variants in each cohort. We also genotyped a commonMUC5Bpromoter variant that is over-represented in individuals with IPF.

Results

We found 15 mutations in 14 individuals (11%) in the IPF cohort: (SFTPA2(n=1),SFTPC(n=5),ABCA3(n=4) andTERT(n=5)). No individual with IPF had two different mutations, but one individual with IPF was homozygous for p.E292V, the most commonABCA3disease-causing variant. We did not detect an interaction between any of the mutations and theMUC5Bpromoter variant.

Conclusions

Rare mutations inSFTPA2,SFTPCandTERTare collectively over-represented in individuals with IPF. Genetic analysis and counselling should be considered as part of the IPF evaluation.
Growth of a vapour bubble in a viscous, superheated liquid in two-phase flow
Authors: Mohammadein S.A. , Mohamed K.G.
Published: December 2014

This paper presents the growth of a vapour bubble in a viscous, superheated liquid. The problem is solved analytically using the Plesset and Zwick method after modifying the pressure difference to include a multiple quantity of the initial pressure difference, its coefficient b giving the necessary condition for the growth process. Relations between the initial and final times in terms of the given physical parameters are derived. The bubble radius is proportional to the thermal diffusivity, the initial pressure difference and its coefficient, while it is inversely proportional to the surface tension, the dynamic viscosity, and the initial void fraction. Moreover, for b = 1 × 10−2, better agreement is achieved to some experimental data than some previous theoretical works, for the initial superheated conditions at 2.1, 3.1, and 4.5 K.
Quantum star-graph analogues of PT -symmetric square wells: Part II, spectra
Authors: Znojil Miloslav
Published: December 2014

For the non-Hermitian equilateral q-pointed star-shaped quantum graphs of our previous paper (Can. J. Phys. 90, 1287 (2012) doi:10.1139/p2012-107 ) we show that because of certain dynamical aspects of the model as controlled by the external, rotation-symmetric complex Robin boundary conditions, the spectrum is obtainable in a closed asymptotic-expansion form, in principle at least. Explicit formulae up to the second order are derived for illustration, and a few comments on their consequences are added.
Authentication of Ginkgo biloba herbal dietary supplements using DNA barcoding
Authors: Little Damon P.
Published: December 2014

Ginkgo biloba L. (known as ginkgo or maidenhair tree) is a phylogenetically isolated, charismatic, gymnosperm tree. Herbal dietary supplements, prepared from G. biloba leaves, are consumed to boost cognitive capacity via improved blood perfusion and mitochondrial function. A novel DNA mini-barcode assay was designed and validated for the authentication of G. biloba in herbal dietary supplements (n = 22; sensitivity = 1.00, 95% CI = 0.59–1.00; specificity = 1.00, 95% CI = 0.64–1.00). This assay was further used to estimate the frequency of mislabeled ginkgo herbal dietary supplements on the market in the United States of America: DNA amenable to PCR could not be extracted from three (7.5%) of the 40 supplements sampled, 31 of 37 (83.8%) assayable supplements contained identifiable G. biloba DNA, and six supplements (16.2%) contained fillers without any detectable G. biloba DNA. It is hoped that this assay will be used by supplement manufacturers to ensure that their supplements contain G. biloba.
Integro-differential Schrödinger equation and description of unstable particle
Authors: Fa Kwok Sau
Published: December 2014

The description of a particle in the quantum system is probabilistic. In the ordinary quantum mechanics the total probability of finding the particle is conserved, i.e. the probability is normalized for all the times. To find a non-constant total probability an imaginary term should be added to the potential energy which is not physical. Recently, generalizations of the ordinary Schrödinger equation have been proposed by using the Feynman path integral and analogy between the Schrödinger equation and diffusion equation. In this work, an integro-differential Schrödinger equation is proposed by using analogy between the Schrödinger equation and diffusion equation. The equation is obtained from the continuous time random walk model with diverging jump length variance and generic waiting time probability density. The equation generalizes the ordinary and fractional Schrödinger equations. One can show that the integro-differential Schrödinger equation can describe a non-constant total probability for a free particle, and it includes the exponential decay which is fundamental for the description of radioactive decay.
Adsorption of molecular oxygen on VIIIB transition metal-doped graphene: A DFT study
Authors: Nasehnia F. , Seifi M.
Published: December 2014

Adsorption of molecular oxygen with a triplet ground state on Fe -, Co -, Ni -, Ru -, Rh -, Pd -, OS -, Ir - and Pt -doped graphene is studied using density functional theory (DFT) calculations. The calculations show that O 2 molecule is chemisorbed on the doped graphene sheets with large adsorption energies ranging from -0.653 eV to -1.851 eV and the adsorption process is irreversible. Mulliken atomic charge analysis of the structure shows that charge transfer from doped graphene sheets to O 2 molecule. The amounts of transferred charge are between 0.375e- to 0.650e-, indicating a considerable change in the structures conductance. These results imply that the effect of O 2 adsorption on transition metal-doped graphene structures can alter the possibility of using these materials as a toxic-gas (carbon monoxide, hydrogen fluoride, etc.) sensor.
Spatiotemporal chemotactic model for ant foraging
Authors: Ramakrishnan Subramanian , Laurent Thomas , Kumar Manish , Bertozzi Andrea L.
Published: December 2014

In this paper, we present a generic theoretical chemotactic model that accounts for certain emergent behaviors observed in ant foraging. The model does not have many of the constraints and limitations of existing models for ants colony dynamics and takes into account the distinctly different behaviors exhibited in nature by ant foragers in search of food and food ferrying ants. Numerical simulations based on the model show trail formation in foraging ant colonies to be an emergent phenomenon and, in particular, replicate behavior observed in experiments involving the species P. megacephala. The results have broader implications for the study of randomness in chemotactic models. Potential applications include the developments of novel algorithms for stochastic search in engineered complex systems such as robotic swarms.
Spherically symmetric vacuum solutions arising from trace dynamics modifications to gravitation
Authors: Adler Stephen L. , Ramazanoğlu Fethi M.
Published: December 2014

We derive the equations governing static, spherically symmetric vacuum solutions to the Einstein equations, as modified by the frame-dependent effective action (derived from trace dynamics) that gives an alternative explanation of the origin of "dark energy". We give analytic and numerical results for the solutions of these equations, first in polar coordinates, and then in isotropic coordinates. General features of the static case are that: (i) there is no horizon, since g00 is nonvanishing for finite values of the polar radius, and only vanishes (in isotropic coordinates) at the internal singularity, (ii) the Ricci scalar R vanishes identically, and (iii) there is a physical singularity at cosmological distances. The large distance singularity may be an artifact of the static restriction, since we find that the behavior at large distances is altered in a time-dependent solution using the McVittie Ansatz.
CD44 Antibody-Conjugated Gold Nanostars as SERS Probes for Distinguishing Cancer Cells (A549 Cells, H1229 Cells) from Normal Cells (ATII Cells)
Authors: Zhao Hang , Cao Xiaowei , Wang Man , Tao Lin , Pan Xiaoyu , Yuan Chunwei , Qian Weiping
Published: December 2014

In this paper, we report a novel antibody conjugated gold nanostars ( AuNSs ) as surface-enhanced Raman spectroscopy (SERS) probes for distinguishing cancer cells (A549 cells, H1229 cells) from normal cells (ATII cells). In such a probe, bovine serum albumin (BSA) was served as the protective agent and stabilizing agent, 4-mercaptobenzoic acid (4-MBA) was used as the Raman reporter to generate SERS signals as well as the conjugation agent for attaching CD44 antibody (anti-CD44) molecules to AuNSs , where anti-CD44 could effectively target to CD44 protein over-expressed cells. All the results of the experiments confirmed that more SERS probes have been targeted to cancer cells (A549 cells and H1229 cells) than that of normal cells (ATII cells) under the same condition. The anti-CD44 SERS probes hold a potential application in distinguishing cancer cells from normal cells with high sensitivity and good biocompatibility.
Global stability of an SEIQV epidemic model with general incidence rate
Authors: Yang Yu , Zhang Cuimei , Jiang Xunyan
Published: December 2014

In this paper, a class of SEIQV epidemic model with general nonlinear incidence rate is investigated. By constructing Lyapunov function, it is shown that the disease-free equilibrium is globally asymptotically stable if the basic reproduction number ℛ0≤ 1. If ℛ0> 1, we show that the endemic equilibrium is globally asymptotically stable by applying Li and Muldowney geometric approach.
Henry Culpin (1861–1912): a Yorkshire geologist and palaeontologist, and his collection in the Doncaster Museum and Art Gallery, South Yorkshire
Authors: Lomax Dean R.
Published: December 2014

Henry Culpin was an autodidact geologist and palaeontologist; he was among the first of very few local people to understand and describe the geological outcrops, and fossils within them, around Doncaster, South Yorkshire. During his excursions, Culpin collected many fossil specimens and gifted several to Beechfield House museum, now Doncaster Museum and Art Gallery. A large percentage of these specimens are of local origin, collected from Carboniferous coal mine deposits that are no longer accessible. They represent some of the most scientifically and locally important fossils from Doncaster, collected when some of the earliest mine shafts were being sunk in the district.

Supplementary material:

The entire list of records from the Doncaster Museum accession register is available at:
http://www.geolsoc.org.uk/SUP18783
A dearth of diplobathrids (Crinoidea) from the type Devonian System, SW England
Authors: Donovan Stephen K. , Fearnhead Fiona E.
Published: December 2014

The diverse biota from the marine deposits of the type area of the Devonian System was monographed by the Reverend George Ferris Whidborne, MA, FGS (1846–1910) between 1889 and 1907. Most well-preserved specimens of crinoids are cladids or monobathrids from the Middle and Upper Devonian of south and north Devon, respectively. The camerate crinoids are dominated by the monobathrid
Hexacrinites
spp., known from many thecae and several nominal species from the Middle Devonian Torquay Limestone Formation; other monobathrids are moderately common in the Upper Devonian. The dicyclic diplobathrid camerates are less speciose and are commonly poorly preserved. Diplobathrids include
Rhodocrinites
? sp. A (poor crown) and
Rhodocrinites
? sp. B (columnals);
Acanthocrinus
sp. (spinose thecal plate);
Gilbertsocrinus
sp. A (columnals); non
Rhipidocrinus crenatus
(Goldfuss) (possibly a monobathrid crown);
Thylacrinus
? sp. (fragment of theca); and rhodocrinitid? sp. indet. This is in stark contrast to the 5 genera and 9 nominal species of diplobathrids known from the lower Silurian, and the 3 genera and 14 nominal species in the Mississippian of the British Isles, many of which are known from multiple, well-preserved specimens. The potential reasons for this disparity are many, but must include lack of effort by collectors over the past 100+ years, limited outcrop area, poor preservation due to tectonic deformation and, probably, a genuine rarity of diplobathrids in the British Isles during the Devonian.
Nestin-mediated cytoskeletal remodeling in endothelial cells: novel mechanistic insight into VEGF-induced cell migration in angiogenesis
Authors: Liang Zhen-wei , Wang Zheng , Chen Hui , Li Cen , Zhou Ti , Yang Zhonghan , Yang Xia , Yang Yanfang , Gao Guoquan , Cai Weibin
Published: December 2014

Nestin is highly expressed in poorly differentiated and newly formed proliferating endothelial cells (ECs); however, the role of this protein in angiogenesis remains unknown. Additionally, the cytoskeleton and associated cytoskeleton-binding proteins mediate the migration of vascular ECs. Therefore, the aim of the present study was to determine whether VEGF regulates the cytoskeleton, as well as other associated proteins, to promote the migration of vascular ECs. The coexpression of nestin and CD31 during angiogenesis in alkali-burned rat corneas was examined via immunohistochemical analysis. Western blot analyses revealed that the exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia promoted nestin expression in vitro. Additionally, nestin silencing via siRNA significantly inhibited many of the process associated with VEGF-induced angiogenesis, including tube formation and the migration and proliferation of HUVECs. Moreover, FITC-phalloidin labeling revealed that F-actin filaments were successfully organized into microfilaments in VEGF-treated cells, suggesting a network rearrangement accomplished via F-actin that contrasted with the uniform and loose actin filament network observed in the siRNA-nestin cells. The results of the present study highlight the key role played by nestin in activated HUVECs during angiogenesis. The inhibition of the ERK pathway suppressed the nestin expression induced by VEGF in the HUVECs. Therefore, our study provides the first evidence that nestin-mediated cytoskeleton remodeling in ECs occurs via filopodia formation along the cell edge, facilitating both filopodia localization and cell polarization and ultimately promoting HUVEC migration via VEGF induction, which may be associated with ERK pathway activation.
Loss of Rho-GDIα sensitizes podocytes to lipopolysaccharide-mediated injury
Authors: Robins Richard , Baldwin Cindy , Aoudjit Lamine , Gupta Indra R. , Takano Tomoko
Published: December 2014

Nephrotic syndrome is a disease of glomerular permselectivity that can arise as a consequence of heritable or acquired changes to the integrity of the glomerular filtration barrier. We recently reported two siblings with heritable nephrotic syndrome caused by a loss of function mutation in the gene ARHGDIA, which encodes for Rho guanine nucleotide dissociation inhibitor-α (GDIα). GDIs are known to negatively regulate Rho-GTPase signaling. We hypothesized that loss of GDIα sensitizes podocytes to external injury via hyperactivation of Rho-GTPases and p38 MAPK. We examined the response of cultured podocytes with and without knockdown of GDIα to LPS injury by assessing the levels of phospho-p38 as well as the degree of synaptopodin loss. GDIα knockdown podocytes showed more pronounced and sustained p38 phosphorylation in response to LPS compared with control podocytes, and this was blunted significantly by the Rac1 inhibitor. In LPS-treated control podocytes, synaptopodin degradation occurred, and this was dependent on p38, the proteasome, and cathepsin L. In GDIα knockdown podocytes, the same events were triggered, but the levels of synaptopodin after LPS treatment were significantly lower than in control podocytes. These experiments reveal a common pathway by which heritable and environmental risk factors converge to injure podocytes, from Rac1 hyperactivation to p38 phosphorylation and synaptopodin degradation via the ubiquitin-proteasome pathway and cathepsin L.
TIGAR regulates glycolysis in ischemic kidney proximal tubules
Authors: Kim Jinu , Devalaraja-Narashimha Kishor , Padanilam Babu J.
Published: December 2014

Tp53-induced glycolysis and apoptosis regulator (TIGAR) activation blocks glycolytic ATP synthesis by inhibiting phosphofructokinase-1 activity. Our data indicate that TIGAR is selectively induced and activated in renal outermedullary proximal straight tubules (PSTs) after ischemia-reperfusion injury in a p53-dependent manner. Under severe ischemic conditions, TIGAR expression persisted through 48 h postinjury and induced loss of renal function and histological damage. Furthermore, TIGAR upregulation inhibited phosphofructokinase-1 activity, glucose 6-phosphate dehydrogenase (G6PD) activity, and induced ATP depletion, oxidative stress, autophagy, and apoptosis. Small interfering RNA-mediated TIGAR inhibition prevented the aforementioned malevolent effects and protected the kidneys from functional and histological damage. After mild ischemia, but not severe ischemia, G6PD activity and NADPH levels were restored, suggesting that TIGAR activation may redirect the glycolytic pathway into gluconeogenesis or the pentose phosphate pathway to produce NADPH. The increased level of NADPH maintained the level of GSH to scavenge ROS, resulting in a lower sensitivity of PST cells to injury. Under severe ischemia, G6PD activity and NADPH levels were reduced during reperfusion; however, blockade of TIGAR enhanced their levels and reduced oxidative stress and apoptosis. Collectively, these results demonstrate that inhibition of TIGAR may protect PST cells from energy depletion and apoptotic cell death in the setting of severe ischemia-reperfusion injury. However, under low ischemic burden, TIGAR activation induces the pentose phosphate pathway and autophagy as a protective mechanism.