bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probable transfusion‐transmission of Anaplasma phagocytophilum by leukoreduced platelets
Authors: Townsend Rebecca L. , Moritz Erin D. , Fialkow Lawrence B. , Berardi Victor , Stramer Susan L. 
Published: April 2014

BackgroundAnaplasma phagocytophilum (AP), a tick‐borne obligate intracellular bacterium, causes human granulocytic anaplasmosis (HGA) and has been implicated in seven transfusion‐transmitted (TT)‐HGA cases associated with red blood cells (RBCs). Here we report the first probable case of TT‐HGA involving leukoreduced platelets (PLTs).Case ReportA hospitalized male received 25 blood components (November 2012) before his death from trauma. Hospital testing confirmed HGA by peripheral blood smears; samples were also sent to IMUGEN, Inc. (Norwood, MA), for AP‐polymerase chain reaction (PCR) and AP‐immunoglobulin (Ig)M and IgG enzyme immunoassay. All 12 potentially transmitting donors provided follow‐up samples.ResultsRecipient smears progressed from negative to predominantly positive 16 days posttransfusion; hospital‐performed AP‐PCR was positive on Day 22. IMUGEN sample testing was PCR positive and IgM and IgG negative 14 to 23 days posttransfusion. The recipient had no known AP risk factors. One of 12 donors of RBCs or PLTs (leukoreduced 5‐day‐old PLTs) provided six follow‐up samples; all were strongly IgG positive and IgM negative; one was PCR‐positive. The IgG‐positive donor was a 52‐year‐old female from Hudson Valley, New York, an area endemic for AP. She reported tick bites in September to October 2012 with no travel outside New York. The donor remained asymptomatic and received no treatment. The cocomponent PLT unit was transfused to a 78‐year‐old male who died of causes unrelated to AP.ConclusionsThis eighth case of probable TT‐HGA indicates that leukoreduced PLTs may be infectious. An antibody‐ and PCR‐positive donor having prior tick exposure living in an endemic area was identified. PCR positivity and elevated IgG levels, which continue to exceed the assay's detectible range even in the absence of IgM, indicate active donor infection.
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

BackgroundThe 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 MethodsThe 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.ResultsSanger 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.ConclusionA 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.
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

ABSTRACT
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT
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

ABSTRACT

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

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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.
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.
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

AimIn 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.MethodsWe 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.ResultsDiagnostic 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.ConclusionsCNB appears to be feasible and accurate for diagnosing a MA. Prominent growth patterns of MA are significant factors for successful histologic diagnosis of MA.
Lifestyle Intervention Involving Calorie Restriction with or without Aerobic Exercise Training Improves Liver Fat in Adults with Visceral Adiposity
Authors: Yoshimura Eiichi , Kumahara Hideaki , Tobina Takuro , Matsuda Takuro , Ayabe Makoto , Kiyonaga Akira , Anzai Keizo , Higaki Yasuki , Tanaka Hiroaki 
Published: April 2014

Objective. To evaluate the effect of calorie restriction-induced weight loss with or without aerobic exercise on liver fat.Methods. Thirty-three adults with visceral adiposity were divided into calorie restriction (CR;n = 18) or CR and aerobic exercise (CR + Ex;n = 15) groups. Target energy intake was 25 kcal/kg of ideal body weight. The CR + Ex group had a targeted exercise time of 300 min/wk or more at lactate threshold intensity for 12 weeks.Results. Reductions in body weight (CR,-5.3 ± 0.8 kg; CR + Ex,-5.1 ± 0.7 kg), fat mass (CR,-4.9± 0.9kg; CR + Ex,-4.4 ± 0.6 kg), and visceral fat (CR,-24 ± 5 cm2; CR + Ex,-37 ± 5 cm2) were not statistically different between groups. Liver fat decreased significantly in both groups, with no difference between groups. Change in maximal oxygen uptake was significantly greater in the CR + Ex group than in the CR group (CR,-0.7 ± 0.7 mL/kg/min; CR + Ex,2.9 ± 1.0 mL/kg/min).Conclusion. Both CR and CR + Ex resulted in an improved reduction in liver fat; however, there was no additive effect of exercise training.