bluuebunny/crossref_metadata_2025 huggingface dataset:
Family study of a Swiss patient uncovered a novel genetic basis for the S−s−U+var phenotype
Authors: Saison Carole , Waldvogel Sophie , Gien Dominique , Peyrard Thierry , Arnaud Lionel
Published: April 2014

Background

The rare S−s− phenotype is typically found in persons of African origin. Three genetic bases underlying this phenotype have been identified so far: a large deletion including the GYPB gene, which encodes the S and s antigens, and two mutations affecting GYPB splicing (commonly called “P2” and “NY”). The discovery of the S−s− phenotype in a Swiss patient prompted this study.

Study Design and Methods

The GYPB genotype of the patient was analyzed with Beadchip technology and Sanger sequencing. GYPB haplotype analysis was also carried out in the patient's family. A functional splicing assay was developed to determine the impact of the identified mutation on GYPB splicing.

Results

Sanger sequencing of GYPB in the patient indicated that she was homozygous for a GYPB*s allele carrying a novel mutation in the splice donor site of Intron 5 (c.270+5G>A). Analysis of GYPB haplotypes in the patient's family revealed that she actually inherited this mutated GYPB*s allele from her mother of Swiss ancestry and a deleted GYPB allele from her father of Egyptian ancestry. Using a minigene‐based splicing assay, we showed that GYPB mutation c.270+5G>A causes the skipping of Exon B5, as previously reported for the P2 mutation (c.270+5G>T). Consistently, the patient's red blood cells were found to be S−s−U+var.

Conclusion

A novel GYPB mutation (c.270+5G>A) accounting for the S−s−U+var phenotype was identified. In contrast with P2 and NY mutations, which also drive this rare phenotype, this novel GYPB mutation inactivates a GYPB*s allele and does not appear to be of African origin.
Structural Basis for Assembly and Function of a Heterodimeric Plant Immune Receptor
Authors: Williams Simon J. , Sohn Kee Hoon , Wan Li , Bernoux Maud , Sarris Panagiotis F. , Segonzac Cecile , Ve Thomas , Ma Yan , Saucet Simon B. , Ericsson Daniel J. , Casey Lachlan W. , Lonhienne Thierry , Winzor Donald J. , Zhang Xiaoxiao , Coerdt Anne , Parker Jane E. , Dodds Peter N. , Kobe Bostjan , Jones Jonathan D. G.
Published: April 2014

Universal Immune Function

Certain pathogen effectors are detected in plants by cytoplasmic receptors. First solving the crystal structures of
Arabidopsis
receptors,

Williams
et al.

(p.
299
; see the Perspective by

Nishimura and Dangl

) discovered that in the resting state, the structures form a heterodimer that readies the complex for effector binding and keeps the signaling domains from firing too early. Once the pathogen effector binds, the structure of the complex shifts such that the signaling domains can form a homodimer to initiate downstream signaling. Similarities between these plant-pathogen receptors and Toll-like receptors in animals suggest the molecular mechanisms may translate broadly.
Strong Increase of
T
c
of Sr
2
RuO
4
Under Both Tensile and Compressive Strain
Authors: Hicks Clifford W. , Brodsky Daniel O. , Yelland Edward A. , Gibbs Alexandra S. , Bruin Jan A. N. , Barber Mark E. , Edkins Stephen D. , Nishimura Keigo , Yonezawa Shingo , Maeno Yoshiteru , Mackenzie Andrew P.
Published: April 2014

Strained Superconductor

Distorting a material and observing its response can allow insight into its electronic properties. Thin films can be strained by placing them on a substrate with a different lattice constant; bulk samples present more of a challenge.

Hicks
et al.

(p.
283
) designed an apparatus to apply both tensile and compressive strain and used it to study the properties of the superconductor Sr
2
RuO
4
, which has long been hypothesized to host the unusual p-wave superconductivity. The response of the superconducting transition temperature
T
c
to the applied strain depended on the direction in which the strain was applied, and did not exhibit a cusp predicted to occur around zero strain. As the technique leaves a surface of the probe open to external probes, it could be adopted for a wide range of methods.
Crystal Structure of a Claudin Provides Insight into the Architecture of Tight Junctions
Authors: Suzuki Hiroshi , Nishizawa Tomohiro , Tani Kazutoshi , Yamazaki Yuji , Tamura Atsushi , Ishitani Ryuichiro , Dohmae Naoshi , Tsukita Sachiko , Nureki Osamu , Fujiyoshi Yoshinori
Published: April 2014

How Tight?

In metazoans, sheets of epithelial cells separate different tissue spaces and control their composition. Tight junctions are cell-cell adhesion structures in these cell sheets that form a seal between cells but also provide some selective permeability to ions and small molecules. Claudins are the main constituents of tight junctions, and mutations in claudins cause inherited human disorders involving the disruption of ionic balance.

Suzuki
et al.

(p.
304
) report the structure of mouse claudin-15 at 2.4 angstrom resolution, which shows an extracellular β-sheet domain anchored to a transmembrane four-helix bundle. The electrostatic distribution on the claudin surface reveals a negatively charged groove in the extracellular domain that may provide a pathway for positive ions.
Missing Gas-Phase Source of HONO Inferred from Zeppelin Measurements in the Troposphere
Authors: Li Xin , Rohrer Franz , Hofzumahaus Andreas , Brauers Theo , Häseler Rolf , Bohn Birger , Broch Sebastian , Fuchs Hendrik , Gomm Sebastian , Holland Frank , Jäger Julia , Kaiser Jennifer , Keutsch Frank N. , Lohse Insa , Lu Keding , Tillmann Ralf , Wegener Robert , Wolfe Glenn M. , Mentel Thomas F. , Kiendler-Scharr Astrid , Wahner Andreas
Published: April 2014

On a Zeppelin

Nitrous acid (HONO) is an important atmospheric trace gas that acts as a precursor of tropospheric hydroxyl-radicals (OH), which is responsible for the self-cleansing capacity of the atmosphere and which also controls the concentrations of greenhouse gases, such as methane and ozone. How HONO is made is a mystery. Flying onboard a Zeppelin over the Po Valley in Northern Italy,

Li
et al.

(p.
292
) discovered HONO in the undisturbed morning troposphere, indicating that HONO must be produced there, rather than mixed from the surface. The high HONO concentrations are likely to have been formed by a light-dependent gas-phase source that probably consumed OH or HO2 radicals, which hints that the impact of HONO on the abundance of OH in the entire troposphere may be substantially overestimated.
Enhancing Depression Mechanisms in Midbrain Dopamine Neurons Achieves Homeostatic Resilience
Authors: Friedman Allyson K. , Walsh Jessica J. , Juarez Barbara , Ku Stacy M. , Chaudhury Dipesh , Wang Jing , Li Xianting , Dietz David M. , Pan Nina , Vialou Vincent F. , Neve Rachael L. , Yue Zhenyu , Han Ming-Hu
Published: April 2014

Resilient Hyperpolarization

Despite constant exposure to all sorts of stressors, most people are resilient and do not develop depression, but we do not understand the neurophysiological underpinnings of stress resilience.

Friedman
et al.

(p.
313
) studied this phenomenon in a mouse model of social-defeat stress depression. In the mice they found that, despite apparently pathological levels of hyperpolarization and elevated potassium channel currents in the ventral tegmental area (a structure known to be involved in depression), resilient mice showed normal activity in dopaminergic neurons. Thus, if “depressed” mice were experimentally provoked into hyperpolarization—unexpectedly, they completely reversed depression-related behaviors.
An Earth-Sized Planet in the Habitable Zone of a Cool Star
Authors: Quintana Elisa V. , Barclay Thomas , Raymond Sean N. , Rowe Jason F. , Bolmont Emeline , Caldwell Douglas A. , Howell Steve B. , Kane Stephen R. , Huber Daniel , Crepp Justin R. , Lissauer Jack J. , Ciardi David R. , Coughlin Jeffrey L. , Everett Mark E. , Henze Christopher E. , Horch Elliott , Isaacson Howard , Ford Eric B. , Adams Fred C. , Still Martin , Hunter Roger C. , Quarles Billy , Selsis Franck
Published: April 2014

Starry Brightness

The high photometric precision of NASA's Kepler observatory has enabled the detection of many planets because they cause slight dimming of their host stars as they orbit in front of them. From these data,

Quintana
et al.

(p.
277
) have spotted a five-planet system around a small star. Here, the outermost planet is only 10% larger than Earth and completes its 130-day orbit entirely within the habitable zone, where liquid water could exist on its surface. Similarly, Kepler can detect faint periodic brightenings, as
Kruse and Agol
(p.
275
) have reported for the binary system KOI-3278. In this system, a white dwarf acts as a gravitational microlens when it passes in front of its Sun-like G-star companion every 88 days. The lensing effect allows the mass of the white dwarf to be estimated, which helps us to understand how similar binary systems may have evolved.
Distinct Profiles of Myelin Distribution Along Single Axons of Pyramidal Neurons in the Neocortex
Authors: Tomassy Giulio Srubek , Berger Daniel R. , Chen Hsu-Hsin , Kasthuri Narayanan , Hayworth Kenneth J. , Vercelli Alessandro , Seung H. Sebastian , Lichtman Jeff W. , Arlotta Paola
Published: April 2014

Patchy Insulation

Myelin insulates neuronal axons such that their electrical signals travel faster and more efficiently. However, not all axons are myelinated equally.

Tomassy
et al.

(p.
319
; see the Perspective by

Fields

) obtained detailed images from two snippets of the adult mouse brain and generated three-dimensional reconstructions of individual neurons and their myelination patterns. The images show that some axons have long, unmyelinated stretches, which might offer sites for building new connections. Thus, myelination is not an all-or-none phenomenon but rather is a characteristic of what may be a specific dialogue between the neuron and the surrounding myelin-producing cells.
Avoiding (Re)extinction
Authors: Minteer Ben A. , Collins James P. , Love Karen E. , Puschendorf Robert
Published: April 2014

Alternative methods of identification should be used to avoid collection of voucher specimens of threatened or rediscovered species.
KOI-3278: A Self-Lensing Binary Star System
Authors: Kruse Ethan , Agol Eric
Published: April 2014

Starry Brightness

The high photometric precision of NASA's Kepler observatory has enabled the detection of many planets because they cause slight dimming of their host stars as they orbit in front of them. From these data,

Quintana
et al.

(p.
277
) have spotted a five-planet system around a small star. Here, the outermost planet is only 10% larger than Earth and completes its 130-day orbit entirely within the habitable zone, where liquid water could exist on its surface. Similarly, Kepler can detect faint periodic brightenings, as
Kruse and Agol
(p.
275
) have reported for the binary system KOI-3278. In this system, a white dwarf acts as a gravitational microlens when it passes in front of its Sun-like G-star companion every 88 days. The lensing effect allows the mass of the white dwarf to be estimated, which helps us to understand how similar binary systems may have evolved.
Refractory Plasmonics
Authors: Guler Urcan , Boltasseva Alexandra , Shalaev Vladimir M.
Published: April 2014

Stable at high temperatures, refractory plasmonic materials could boost existing optoelectronic technologies.
Novelty Trumps Loss in Global Biodiversity
Authors: Pandolfi John M. , Lovelock Catherine E.
Published: April 2014

Although global biodiversity is declining, local ecosystems are not systematically losing diversity, but rather experiencing rapid turnover in species.

[Also see Report by

Dornelas
et al.

]
Assessment of Chimpanzee Adenovirus Serotype 63 Neutralizing Antibodies Prior to Evaluation of a Candidate Malaria Vaccine Regimen Based on Viral Vectors
Authors: Nébié Issa , Edwards Nick J. , Tiono Alfred B. , Ewer Katie J. , Sanou Guillaume S. , Soulama Issiaka , Sanon Souleymane , Diarra Amidou , Yaro Jean Baptiste , Kangoye David , Imoukhuede Egeruan B. , Hill Adrian V. S. , Sirima Sodiomon B.
Published: April 2014

Prior to a chimpanzee adenovirus-based (ChAd63) malarial vaccine trial, sera were collected to assess ChAd63-specific neutralizing antibody titers in Banfora (Burkina Faso). The low neutralizing antibody titers reported in both adults and children (median titers, 139.1 and 35.0, respectively) are encouraging for the potential use of ChAd63 as a malarial vaccine vector.
Comparison of FecalSwab and ESwab Devices for Storage and Transportation of Diarrheagenic Bacteria
Authors: Hirvonen Jari J. , Kaukoranta Suvi-Sirkku
Published: April 2014

Using a collection (
n
= 12) of ATCC and known stock isolates, as well as 328 clinical stool specimens, we evaluated the ESwab and the new FecalSwab liquid-based microbiology (LBM) devices for storing and transporting diarrheagenic bacteria. The stock isolates were stored in these swab devices up to 48 h at refrigeration (4°C) or room (∼25°C) temperature and up to 3 months at −20°C or −70°C. With the clinical stool specimens, the performances of the ESwab and FecalSwab were compared to those of routinely used transport systems (Amies gel swabs and dry containers). At a refrigeration temperature, all isolates survived in FecalSwab up to 48 h, while in ESwab, only 10 isolates (83.3%) out of 12 survived. At −70°C, all isolates in FecalSwab were recovered after 3 months of storage, whereas in ESwab, none of the isolates were recovered. At −20°C, neither of the swab devices preserved the viability of stock isolates after 2 weeks of storage, and at room temperature, 7 (58.3%) of the stock isolates were recovered in both transport devices after 48 h. Of the 328 fecal specimens, 44 (13.4%) were positive for one of the common diarrheagenic bacterial species with all transport systems used. Thus, the suitability of the ESwab and FecalSwab devices for culturing fresh stools was at least equal to those of the Amies gel swabs and dry containers. Although the ESwab was shown to be an option for collecting and transporting fecal specimens, the FecalSwab device had clearly better preserving properties under different storage conditions.
First Report of Mycobacterium canariasense Catheter-Related Bacteremia in the Americas
Authors: Paniz-Mondolfi Alberto , Ladutko Lynn , Brown-Elliott Barbara A. , Vasireddy Ravikiran , Vasireddy Sruthi , Wallace Richard J. , Jakubiec Wesley , Brecher Stephen , Campbell Sheldon
Published: April 2014

Mycobacterium canariasense
is a recently described late-pigmenting, rapidly growing mycobacterium linked to bacteremia in patients with underlying malignant diseases. We report a case of
M. canariasense
infection in a patient from Massachusetts with underlying diffuse B cell lymphoma, which was identified both by multilocus sequence typing and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). To our knowledge, this is the first description after its original identification in Spain and the first report of this opportunistic pathogen in the Americas.
Expanded Host Diversity and Geographic Distribution of Hantaviruses in Sub-Saharan Africa
Authors: Kang Hae Ji , Stanley William T. , Esselstyn Jacob A. , Gu Se Hun , Yanagihara Richard
Published: April 2014

The recent discovery of hantaviruses in shrews and bats in West Africa suggests that other genetically distinct hantaviruses exist in East Africa. Genetic and phylogenetic analyses of newfound hantaviruses, detected in archival tissues from the Geata mouse shrew (
Myosorex geata
) and Kilimanjaro mouse shrew (
Myosorex zinki
) captured in Tanzania, expands the host diversity and geographic distribution of hantaviruses and suggests that ancestral shrews and/or bats may have served as the original mammalian hosts of primordial hantaviruses.
Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Can Induce Chromosomal Instability through Targeted Degradation of the Mitotic Checkpoint Kinase Bub1
Authors: Sun Zhiguo , Xiao Bingyi , Jha Hem Chandra , Lu Jie , Banerjee Shuvomoy , Robertson Erle S.
Published: April 2014

Kaposi's sarcoma-associated herpesvirus (KSHV) has a significant contributory role in the development of three major human neoplastic or lymphoproliferative diseases: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). These diseases are associated with chromosomal instability, a hallmark of human cancer. The latency-associated nuclear antigen (LANA) encoded by KSHV plays a key role in regulating a number of cellular pathways critical for oncogenesis. KSHV LANA alone can induce the development of B-cell hyperplasia and lymphoma in mice expressing LANA. LANA also induces chromosomal instability, thus promoting oncogenesis. However, the precise mechanism underlying LANA-mediated chromosomal instability remains uncharted. Here we report that LANA promoted the induction of chromosomal instability and the formation of micronuclei and multinucleation through its interaction with one of the critical spindle checkpoint proteins, Bub1, and the resulting degradation of Bub1. This interaction occurs through the Knl and kinase domains of Bub1, identified as important for stability and degradation. These results suggest that LANA can dysregulate Bub1 activity, which leads to aberrant chromosome replication and aneuploidy, thus contributing to KSHV-mediated oncogenesis.

IMPORTANCE
This work represents the first set of results identifying a novel mechanism by which LANA, a latency-associated antigen encoded by KSHV, can induce the degradation of Bub1, a spindle checkpoint protein that is important for spindle checkpoint signaling and chromosome segregation. The downregulation of Bub1 mediated by LANA resulted in chromosomal instability, a hallmark of cancer. We further investigated the specific domains of Bub1 that are required for the interaction between LANA and Bub1. The results demonstrated that the Knl and kinase domains of Bub1 are required for the interaction between LANA and Bub1. In addition, we also investigated the mechanism by which LANA promoted Bub1 degradation. Our results showed that LANA interacted physically with the anaphase-promoting complex (APC/C), thus promoting the degradation of Bub1 in a ubiquitin-dependent process.
Small-Molecule Probes Targeting the Viral PPxY-Host Nedd4 Interface Block Egress of a Broad Range of RNA Viruses
Authors: Han Ziying , Lu Jianhong , Liu Yuliang , Davis Benjamin , Lee Michael S. , Olson Mark A. , Ruthel Gordon , Freedman Bruce D. , Schnell Matthias J. , Wrobel Jay E. , Reitz Allen B. , Harty Ronald N.
Published: April 2014

Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an
in silico
screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system, we identified small-molecule hit 1 that inhibited Nedd4-PPxY interaction and PPxY-dependent budding. This lead candidate was subsequently improved with additional structure-activity relationship (SAR) analog testing which enhanced antibudding activity into the nanomolar range. Current lead compounds 4 and 5 exhibit on-target effects by specifically blocking the MARV VP40 PPxY-host Nedd4 interaction and subsequent PPxY-dependent egress of MARV VP40 VLPs. In addition, lead compounds 4 and 5 exhibited antibudding activity against Ebola and Lassa fever VLPs, as well as vesicular stomatitis and rabies viruses (VSV and RABV, respectively). These data provide target validation and suggest that inhibition of the PPxY-Nedd4 interaction can serve as the basis for the development of a novel class of broad-spectrum, host-oriented antivirals targeting viruses that depend on a functional PPxY L domain for efficient egress.

IMPORTANCE
There is an urgent and unmet need for the development of safe and effective therapeutics against biodefense and high-priority pathogens, including filoviruses (Ebola and Marburg) and arenaviruses (e.g., Lassa and Junin) which cause severe hemorrhagic fever syndromes with high mortality rates. We along with others have established that efficient budding of filoviruses, arenaviruses, and other viruses is critically dependent on the subversion of host proteins. As disruption of virus budding would prevent virus dissemination, identification of small-molecule compounds that block these critical viral-host interactions should effectively block disease progression and transmission. Our findings provide validation for targeting these virus-host interactions as we have identified lead inhibitors with broad-spectrum antiviral activity. In addition, such inhibitors might prove useful for newly emerging RNA viruses for which no therapeutics would be available.
Herpes Simplex Virus Protein Kinases US3 and UL13 Modulate VP11/12 Phosphorylation, Virion Packaging, and Phosphatidylinositol 3-Kinase/Akt Signaling Activity
Authors: Eaton Heather E. , Saffran Holly A. , Wu Frederick W. , Quach Kevin , Smiley James R.
Published: April 2014

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays key roles in diverse cellular activities and promotes cell growth and survival. It is therefore unsurprising that most viruses modify this pathway in order to facilitate their replication and spread. Previous work has suggested that the herpes simplex virus 1 (HSV-1) tegument proteins VP11/12 and US3 protein kinase modulate the PI3K/Akt pathway, albeit in opposing ways: VP11/12 binds and activates Src family kinases (SFKs), is tyrosine phosphorylated, recruits PI3K in an SFK-dependent fashion, and is required for HSV-induced phosphorylation of Akt on its activating residues; in contrast, US3 inhibits Akt activation and directly phosphorylates downstream Akt targets. We examined if US3 negatively regulates Akt by dampening the signaling activity of VP11/12. Consistent with this hypothesis, the enhanced Akt activation that occurs during US3-null infection requires VP11/12 and correlates with an increase in SFK-dependent VP11/12 tyrosine phosphorylation. In addition, deleting US3 leads to a striking increase in the relative abundances of several VP11/12 species that migrate with reduced mobility during SDS-PAGE. These forms arise through phosphorylation, strictly require the viral UL13 protein kinase, and are excluded from virions. Taken in combination, these data indicate that US3 dampens SFK-dependent tyrosine and UL13-dependent serine/threonine phosphorylation of VP11/12, thereby inhibiting VP11/12 signaling and promoting virion packaging of VP11/12. These results illustrate that protein phosphorylation events mediated by viral protein kinases serve to coordinate the roles of VP11/12 as a virion component and intracellular signaling molecule.

IMPORTANCE
Herpesvirus tegument proteins play dual roles during the viral life cycle, serving both as structural components of the virus particle and as modulators of cellular and viral functions in infected cells. How these two roles are coordinated during infection and virion assembly is a fundamental and largely unanswered question. Here we addressed this issue with herpes simplex virus VP11/12, a tegument protein that activates the cellular PI3K/Akt signaling pathway. We showed that protein phosphorylation mediated by the viral US3 and UL13 kinases serves to orchestrate its functions: UL13 appears to inhibit VP11/12 virion packaging, while US3 antagonizes UL13 action and independently dampens VP11/12 signaling activity.
Chimeric GII.4 Norovirus Virus-Like-Particle-Based Vaccines Induce Broadly Blocking Immune Responses
Authors: Debbink Kari , Lindesmith Lisa C. , Donaldson Eric F. , Swanstrom Jesica , Baric Ralph S.
Published: April 2014

There is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations.

IMPORTANCE
Noroviruses are gastrointestinal pathogens that infect an estimated 21 million people per year in the United States alone. GII.4 noroviruses account for >70% of all outbreaks, making them the most clinically important genotype. GII.4 noroviruses undergo a pattern of epochal evolution, resulting in the emergence of new strains with altered antigenicity over time, complicating vaccine design. This work is relevant to norovirus vaccine design as it demonstrates the potential for development of a chimeric VLP-based vaccine platform that may broaden the protective response against multiple GII.4 strains and proposes a potential reformulation strategy to control newly emergent strains in the human population.
Phosphorylation of Highly Conserved Serine Residues in the Influenza A Virus Nuclear Export Protein NEP Plays a Minor Role in Viral Growth in Human Cells and Mice
Authors: Reuther Peter , Giese Sebastian , Götz Veronika , Riegger David , Schwemmle Martin
Published: April 2014

Phosphorylation at the highly conserved serine residues S23 to S25 in the nuclear export protein (NEP) of influenza A viruses was suspected to regulate its nuclear export activity or polymerase activity-enhancing function. Mutation of these phosphoacceptor sites to either alanine or aspartic acid showed only a minor effect on both activities but revealed the presence of other phosphoacceptor sites that might be involved in regulating NEP activity.
Friend or foe? Figuring out the difference between FPIES, IgE-mediated allergy and food intolerance
Authors: Halbrich Michelle , Ben-Shoshan Moshe , Rex Gregory
Published: April 2014

Most physicians recognise the severe nature of the anaphylactic reactions associated with IgE-mediated food allergy. Adverse reactions to food involving non-IgE mechanisms are often less well understood and are often not diagnosed. Food protein-induced enterocolitis syndrome (FPIES) is an example of a severe non-IgE immune-mediated food reaction that is part of a spectrum of what is believed to be T-cell-mediated reactions. FPIES results in excessive emesis and diarrhoea hours after ingestion of the offending food. While common triggers include milk, soy, wheat and oat, some children may have multiple triggers, leading to malnutrition from lack of food options and unusual developmental concerns related to food aversion.
Choroidoretinal granuloma in a young female patient
Authors: Massa Horace F , Gatzioufas Zisis , Mangioris Georgios , Panos Georgios D
Published: April 2014

A 16-year-old Brazilian female patient presented with blurring of vision in the right eye. Corrected visual acuity was OD 2/20, OS 20/20. Afferent pupillary defect was absent and anterior segment examination revealed anterior uveitis. Fundus examination showed light vitritis and a raised grey–white granuloma located at posterior pole with focal serous retinal detachment on optical coherence. Indocyacnine green angiography disclosed a complete mask effect in granuloma's area. Differential diagnoses were infectious (bacterial, viral, fungal and parasites) diseases, systemic inflammatory diseases, tumours. Blood serologies (HIV, toxoplasma, Borrelia, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubeola) showed positive results for IgM and IgG for toxoplasma, and anterior chamber tap (PCR for toxoplasma, CMV, HSV, VZV) revealed toxoplasma DNA. Anti-toxoplasma therapy, pyrimethamine, sulfadiazine and calcium folinate, was administered immediately. On follow-up granuloma regression was observed, with complete visual restoration. This case demonstrates a clinically challenging posterior pole granuloma.
Clinicoradiological improvement of intracranial tubercular abscess with medical management alone
Authors: Jain Rajendra Singh , Handa Rahul , Nagpal Kadam , Prakash Swayam
Published: April 2014

Tubercular abscess is a rare presentation of central nervous system tuberculosis (TB), which commonly presents as tuberculoma or meningitis. Most of the published cases of tubercular brain abscess have been dealt with by surgical treatment along with medical management. We here report a case of intracranial tubercular abscess in a 17-year-old girl presenting with fever, headache and right hemiparesis who showed significant clinicoradiological improvement with medical management alone. Thus, in a country like India where TB is highly endemic, TB should be considered as a possible aetiology for any intracranial lesion with radiological appearance suggestive of an abscess and surgical treatment can be kept as an option in case of neurological deficits, hydrocephalus or treatment failure.
Extensive warfarin-induced skin necrosis successfully treated with negative pressure wound therapy
Authors: A Murad Aizuri , Daly Toddy , Mulligan Niall , Lenane Patsy
Published: April 2014

A 55-year-old woman presented with an extensive warfarin-induced skin necrosis while an inpatient for treatment of a pulmonary embolism and thromboembolic stroke. She had a background of diabetes mellitus, hypertension and dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low-molecular weight heparin. The wound was successfully treated with a combination of antibiotic, debridement and negative pressure wound therapy.
Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight loss treatment
Authors: Pikkel Yoav Yechezkel
Published: April 2014

A 54-year-old male patient presented to our clinic with acute angle-closure glaucoma and panuveitis in both eyes after being treated with topiramate for binge eating and obesity. This case report emphasises the hazardous side effects of treatment with topiramate with unusual indication and the precaution a caretaker must take when treating a patient.
Misidentification ofMycobacterium fortuitumin an immunocompetent patient presenting with a unilateral neck mass
Authors: Kanzara Todd , Hall Andy , Namnyak Simon , Owa Tony
Published: April 2014

A 31-year-old African man with a blameless medical history presented with an enlarging neck swelling of 6 months duration. He was systemically well with normal heamatobiochemistry. MRI of the neck demonstrated abnormal signalling in the subcutaneous fat overlying the posterior spinal muscles in the midline and the left sternocleidomastoid muscle. Scanty growth ofRhodococcus equiwas reported from a turbid fine needle aspirate of the neck on two separate occasions. The swelling progressed despite numerous antibiotic combinations which necessitated surgical debridement. Analysis of debrided tissue using 16S rDNA surprisingly identifiedMycobacterium fortuitum, notR equi, thereby resolving our diagnostic conundrum.
‘Between the flags’: implementing a rapid response system at scale
Authors: Hughes Clifford , Pain Charles , Braithwaite Jeffrey , Hillman Kenneth
Published: April 2014

While many hospitals are implementing rapid response systems (RRSs) to attend to deteriorating patients in a systematic way, there is little documented evidence on system-wide approaches to adopting RRSs. Here, we report on an initiative which enrolled 220 hospitals in New South Wales, Australia. The ‘between the flags’ approach was modelled on Australia's surf lifesaving experience, where qualified lifesavers perform thousands of rescues each year. Patients in hospitals who are identified as being ‘between the flags’ are given special attention, just like beach goers.
Reliability of small biopsy or cytology for the diagnosis of pulmonary mucinous adenocarcinoma
Authors: Lee Hee Young , Lee Ho Yun , Lee Kyung Soo , Kwon O Jung , Shim Young Mog , Han Joungho
Published: April 2014

Aim

In case of mucinous adenocarcinoma (MA), cytologic atypia is usually mild to moderate, or may be absent in some cases, incurring a diagnostic pitfall in recognising MA in small tissue biopsy and cytology specimens. The purpose of this study was to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (FNA) or core needle biopsy (CNB) for making a diagnosis of pulmonary MA.

Methods

We retrospectively reviewed a consecutive series of 185 patients who underwent curative operation for MA. Among those patients, 105 patients underwent preoperative percutaneous FNA (n=34) or CNB (n=79). Eight patients underwent FNA and CNB for the same tumour. Diagnostic accuracies of FNA and CNB for making a diagnosis of MA were evaluated, and the contribution of various clinicopathologic parameters to subtyping accuracy was analysed.

Results

Diagnostic accuracies of FNA and CNB in determining malignancy were 67.6% and 87.3%, respectively, and those for making a diagnosis of MA were 20.6% and 59.5%, respectively. Univariate analysis indicated that the type of biopsy procedure and prominent growth pattern of MA are significant factors for successful histologic diagnosis. Tumour nature on CT and the length of biopsy specimen were not related to successful diagnosis of histology subtyping of MA.

Conclusions

CNB appears to be feasible and accurate for diagnosing a MA. Prominent growth patterns of MA are significant factors for successful histologic diagnosis of MA.
Molecular mapping of three male-sterile, female-fertile mutants and generation of a comprehensive map of all known male sterility genes in soybean
Authors: Yang Yang , Speth Benjamin D. , Boonyoo Napatsakorn , Baumert Eric , Atkinson Taylor R. , Palmer Reid G. , Sandhu Devinder
Published: April 2014

In soybean, an environmentally stable male sterility system is vital for making hybrid seed production commercially viable. Eleven male-sterile, female-fertile mutants (ms1, ms2, ms3, ms4, ms5, ms6, ms7, ms8, ms9, msMOS, and msp) have been identified in soybean. Of these, eight (ms2, ms3, ms5, ms7, ms8, ms9, msMOS, and msp) have been mapped to soybean chromosomes. The objectives of this study were to (i) locate the ms1, ms4, and ms6 genes to soybean chromosomes; (ii) generate genetic linkage maps of the regions containing these genes; and (iii) develop a comprehensive map of all known male-sterile, female-fertile genes in soybean. The bulked segregant analysis technique was used to locate genes to soybean chromosomes. Microsatellite markers from the corresponding chromosomes were used on F2 populations to generate genetic linkage maps. The ms1 and ms6 genes were located on chromosome 13 (molecular linkage group F) and ms4 was present on chromosome 2 (molecular linkage group D1b). Molecular analyses revealed markers Satt516, BARCSOYSSR_02_1539, and AW186493 were located closest to ms1, ms4, and ms6, respectively. The ms1 and ms6 genes, although present on the same chromosome, were independently assorting with a genetic distance of 73.7 cM. Using information from this study and compiled information from previously published male sterility genes in soybean, a comprehensive genetic linkage map was generated. Eleven male sterility genes were present on seven soybean chromosomes. Four genes were present in two regions on chromosome 2 (molecular linkage group D1b) and two genes were present on chromosome 13 (molecular linkage group F).
Determination of charged Higgs couplings at the LHC
Authors: Gong Xue , Si Zong-Guo , Yang Shuo , Zheng Ya-Juan
Published: April 2014

We review the study of the charged Higgs and top quark associated production at the LHC with the presence of an additional scalar doublet. Top quark spin effects are related to the Higgs fermion couplings through this process. The angular distributions with respect to top quark spin turns out to be distinctive observables to study the Htb interaction in different models.
Off-shell D-brane/F-theory effective superpotentials and Ooguri–Vafa invariants of several compact Calabi–Yau manifolds
Authors: Cheng Shi , Xu Feng-Jun , Yang Fu-Zhong
Published: April 2014

According to the open-closed mirror symmetry and generalized Gel'fand–Kapranov–Zelerinski (GKZ) system, we calculate off-shell D-brane/F-theory effective superpotentials of four compact Calabi–Yau (CY) manifolds by integrating special periods of subsystem, and extracting the open Ooguri–Vafa invariants from the expansion of off-shell D-brane superpotentials.
Anomalies and renormalization of mixed states in quantum theories
Authors: Gupta Kumar S. , de Queiroz Amilcar
Published: April 2014

In a Hamiltonian approach to anomalies, parity and time-reversal symmetries can be restored by introducing suitable impure (or mixed) states. However, the expectation values of observables such as the Hamiltonian diverges in such impure states. Here, we show that such divergent expectation values can be treated within a renormalization group (RG) framework, leading to a set of β-functions in the moduli space of the operators representing the observables. This leads to well-defined expectation values of the Hamiltonian in a phase where the impure state restores the P and T symmetry. We also show that this RG procedure leads to a mass gap in the spectrum. Such a framework may be relevant for long wavelength descriptions of condensed matter systems such as the quantum spin Hall (QSH) effect.
Quarkonia production at LHCb
Authors: Manca G.
Published: April 2014

The recent and ongoing studies in quarkonium physics at LHCb are reviewed and future prospects are given in the field of quarkonium physics.
AN ANALYSIS OF THE ROOT CAUSES OF DEFECTS INJECTED INTO THE SOFTWARE BY THE SOFTWARE TEAM: AN INDUSTRIAL STUDY OF THE DISTRIBUTED HEALTH-CARE SYSTEM
Authors: YANG CHI-LU , CHANG YEIM-KUAN , CHU CHIH-PING
Published: April 2014

A root cause is a source of software defect, whose removal decreases or removes the defect. A root cause of software defect is injected into the software by software engineers during the development process. One of the main concerns of the software team leader, such as the project manager, is to determine who injected various root causes of the defects into the software and when these have been injected. In this paper, a cost-benefit scheme is presented, which allows a software team to determine skill weakness and improve team capability. The scheme provides effective in-process feedback based on the causal analysis of software defects. The proposed analysis scheme includes orthogonal root cause definitions, role-based root cause types, and gradational correction actions. In the experiment, the projects of a distributed health-care system are used to verify the efficiency of the proposed scheme. The results show that the root cause ratios (RCR) are 33.8%, 30.6%, 21.9%, 10.7%, and 3.0% in design, implementation, analysis, business and deployment, respectively. The defects in the projects mainly occurred during the design and implementation phases of the projects. Correction activities to enhance the designers’ skills, such as exception handling (40.5%) and DB/data schema (25.0%), are the top priorities that must be addressed by the software team. The findings can help the team leader to determine methods to improve these weaknesses.
Orbital motion and quasi-quantized disk around rotating neutron stars
Authors: Wang Joan Jing , Chang Hsiang-Kuang
Published: April 2014

In accreting neutron star (NS) low-mass X-ray binary (LMXB) systems, NS accretes material from its low-mass companion via a Keplerian disk. In a viscous accretion disk, inflows orbit the NS and spiral in due to dissipative processes, such as the viscous process and collisions of elements. The dynamics of accretion flows in the inner region of an accretion disk is significantly affected by the rotation of NS. The rotation makes NS, thus the spacetime metric, deviate from the originally spherical symmetry, and leads to gravitational quadrupole, on one hand. On the other hand, a rotating NS drags the local inertial frame in its vicinity, which is known as the rotational frame-dragging effect. In this paper, we investigate the orbital motion of accretion flows of accreting NS/LMXBs and demonstrate that the rotational effects of NS result in a band of quasi-quantized structure in the inner region of the accretion disk, which is different, in nature, from the scenario in the strong gravity of black hole arising from the resonance for frequencies related to epicyclic and orbital motions. We also demonstrate that such a disk structure may account for frequencies seen in X-ray variability, such as quasi-periodic oscillations (QPOs), and can be a potential promising tool for the investigation of photon polarization.
Using Timed Automata for a Priori Warnings and Planning for Timed Declarative Process Models
Authors: Maggi Fabrizio Maria , Westergaard Michael
Published: April 2014

Many processes are characterized by high variability, making traditional process modeling languages cumbersome or even impossible to be used for their description. This is especially true in cooperative environments relying heavily on human knowledge. Declarative languages, like Declare, alleviate this issue by not describing what to do step-by-step but by defining a set of constraints between actions that must not be violated during the process execution. Furthermore, in modern cooperative business, time is of utmost importance. Therefore, declarative process models should be able to take this dimension into consideration. Timed Declare has already previously been introduced to monitor temporal constraints at runtime, but it has until now only been possible to provide an alert when a constraint has already been violated without the possibility of foreseeing and avoiding such violations. In this paper, we introduce an extended version of Timed Declare with a formal timed semantics for the entire language. The semantics degenerates to the untimed semantics in the expected way. We also introduce a translation to timed automata, which allows us to detect inconsistencies in models prior to execution and to early detect that a certain task is time sensitive. This means that either the task cannot be executed after a deadline (or before a latency), or that constraints are violated unless it is executed before (or after) a certain time. This makes it possible to use declarative process models to provide a priori guidance instead of just a posteriori detecting that an execution is invalid. We also outline how a Declare model with time can be used in resource planning and how Declare has been integrated into CPN Tools.
On 9-centralizer groups
Authors: Jafarian Amiri S. M. , Madadi H. , Rostami H.
Published: April 2014

For a finite group G, let Cent (G) denote the set of centralizers of single elements of G. A group is called n-centralizer if | Cent (G)| = n. In this paper we characterize all 9-centralizer groups. Also, we prove that every 10-centralizer group has even order.
GENDER DIFFERENTIALS IN ANTECEDENTS OF HABITUAL ENTREPRENEURSHIP: IMPETUS FACTORS AND HUMAN CAPITAL
Authors: BARNIR ANAT
Published: April 2014

This study investigates gender differences in the effects of entrepreneurial impetus and human capital on habitual entrepreneurship, defined as starting multiple new ventures in a serial or portfolio manner. Using the Panel Study of Entrepreneurial Dynamics II (PSED II) data on nascent entrepreneurs, the effects of three impetus factors (business opportunity, mentors and nature of work) and four human capital factors (education, employment breadth, managerial experience and entrepreneurial capabilities) are explored in terms of the differential effects they have on habitual entrepreneurship in men and women. Results show an overall greater effect of human capital on women's habitual entrepreneurship than on men's, and that different human capital factors appear to drive multiple startups for women and for men. Analyses also show that different impetus factors drive women and men to start new repeat ventures. Results are discussed in the context of learning theory and entrepreneurial activity.
ENTREPRENEURIAL ACTIVITY AS AN EXTERNALITY OF INWARD FOREIGN DIRECT INVESTMENT IN EMERGING ECONOMIES: PANEL DATA FROM ARGENTINA, BRAZIL, COLOMBIA AND SOUTH AFRICA
Authors: WASHINGTON MICHELLE L. , CHAPMAN ZANETA
Published: April 2014

Many emerging economies seek multiple and diversified means of economic development, including openness to inward foreign direct investment. However, some scholars and protectionists claim this hosting of economic activity on the part of multinational corporations (MNCs) might in fact be detrimental to economic development. This paper seeks to address these concerns by using panel data from Argentina, Brazil, Colombia and South Africa to investigate a mediational relationship among inward foreign direct investment, skilled labor supply and entrepreneurial activity in the emerging economy context. Our results provide empirical evidence of later stage entrepreneurial activity as a spillover effect of inward foreign direct investment and that this indirect effect is fully mediated by the pool of factory workers.
THE BITTER TRUTH: A COMPARATIVE ANALYSIS OF BLACK MALE AND BLACK FEMALE ENTREPRENEURS
Authors: GIBBS SHERRHONDA R.
Published: April 2014

The paper examines variables stated to be central to entrepreneurial success and reports differences between black male and black female entrepreneurs. Variables studied include task-specific efficacy, firm performance and opportunity recognition. Using a sample of 85 males and 58 females, results indicated that although black male and female entrepreneurs are somewhat similar in terms of business environment and demographics (e.g., education levels, years of business industry experience, likelihood of having a business mentor, etc.), black females trailed black male entrepreneurs in firm performance, task-specific efficacy and opportunity recognition. Overall, findings suggest an expressed need to enact specific-policies to increase success rates among this group of understudied entrepreneurs, black females.
Molecular states with two heavy quarks
Authors: Li Ning , Sun Zhi-Feng , Liu Xing , Zhu Shi-Lin
Published: April 2014

Within the one-boson-exchange (OBE) potential model, we perform a coupled-channel study of the possible deuteron-like molecular states with two heavy flavor quarks. In our study, we take into account the S-D mixing and the coupled-channel effect in the flavor space. Interestingly, we predict some molecular states which are suggested to be searched for in the further experiments.
Threshold enhancement phenomena in Y(4260) decays
Authors: Liu Xiao-Hai
Published: April 2014

We investigate several strong and radiative decay modes of Y(4260), by assuming that Y(4260) either is a [Formula: see text] molecular state, or has sizeable couplings with [Formula: see text] and [Formula: see text]. In such ansatzes, obvious threshold enhancements or narrow cusp structures appear quite naturally without introducing a genuine resonance. And we emphasize that the radiative decay modes may be useful for studying [Formula: see text]S-wave scattering.