bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanosome‐autonomous regulation of size and number: the OA1 receptor sustains PMEL expression
Authors: Falletta Paola , Bagnato Paola , Bono Maria , Monticone Massimiliano , Schiaffino Maria Vittoria , Bennett Dorothy C. , Goding Colin R. , Tacchetti Carlo , Valetti Caterina 
Published: March 2014

SummaryLittle is known as to how cells ensure that organelle size and number are coordinated to correctly couple organelle biogenesis to the demands of proliferation or differentiation. OA1 is a melanosome‐associated G‐protein‐coupled receptor involved in melanosome biogenesis during melanocyte differentiation. Cells lacking OA1 contain fewer, but larger, mature melanosomes. Here, we show that OA1 loss of function reduces both the basal expression and the α‐melanocyte‐stimulating hormone/cAMP‐dependent induction of the microphthalmia‐associated transcription factor (MITF), the master regulator of melanocyte differentiation. In turn, this leads to a significant reduction in expression of PMEL, a major melanosomal structural protein, but does not affect tyrosinase and melanin levels. In line with its pivotal role in sensing melanosome maturation, OA1 expression rescues melanosome biogenesis, activates MITF expression and thereby coordinates melanosome size and number, providing a quality control mechanism for the organelle in which resides. Thus, resident sensor receptors can activate a transcriptional cascade to specifically promote organelle biogenesis.
Vascular anastomosis for paediatric renal transplantation and new strategy in low‐weight children
Authors: Gomes Adriano Luís , Koch‐Nogueira Paulo César , de Camargo Maria Fernanda Carvalho , Feltran Luciana de Santis , Baptista‐Silva José Carlos Costa 
Published: March 2014

AbstractThe technical aspects of RT in low‐weight children should be specific, particularly with regard to VA. This retrospective study assesses the main VA options in paediatric RTs and proposes a new strategy for renal artery trajectory when using the Ao and the right iVC. The sample included 81 patients and was categorized into a group of children weighing <16 kg and the other group of children weighing 16 kg or more. The smaller children received the graft predominantly on the Ao and iVC (63%); however, the VA options varied in children weighing more than 16 kg, with anastomoses predominantly to the common iliac vessels (46%). In the first group, when the Ao was the selected vessel for anastomosis on the right side, the trajectory adopted for the transplanted kidney artery was posterior to the iVC. This strategy may reduce the risk of compression of the iVC by the renal artery of the donor kidney and may reconstitute the normal anatomy of the renal artery. Moreover, it did not represent a risk factor for graft loss in this sample.
Mining the Watkins collection of wheat landraces for novel sources of eyespot resistance
Authors: Burt C. , Griffe L. L. , Ridolfini A. P. , Orford S. , Griffiths S. , Nicholson P. 
Published: March 2014

Eyespot is an economically important stem base disease of wheat caused by the soilborne fungal pathogens Oculimacula yallundae and Oculimacula acuformis. The most effective method of controlling the disease is host resistance. However, there are only three genetically characterized resistances in wheat varieties and further sources of resistance are required. Previous studies have identified resistances in wild relatives, but use of these resistances has been limited by linkage drag with deleterious traits exacerbated by low rates of recombination. Therefore, the identification of novel resistances in hexaploid wheat germplasm is desirable. The Watkins collection currently consists of 1056 hexaploid wheat landraces that represent global wheat diversity at the time of its collection in the 1920s and 1930s. As such, it may contain beneficial agronomic traits such as eyespot resistance. The Watkins collection was screened for resistance to O. yallundae based on a glasshouse test of all 1056 accessions and a polytunnel test of 44 accessions selected from a previous field trial. Resistant lines identified in these tests were retested against both O. yallundae and O. acuformis. This identified 17 accessions with resistance to one or both of the pathogen species. From these, two accessions (1190094.1 and 1190736.3) provided a high level of resistance to both pathogen species. An F4 population derived from accession 1190736.3 indicated that the resistance to O. acuformis in this accession is conferred by a single gene and therefore would be suitable for introgression into elite wheat varieties to provide an alternative source of eyespot resistance.
Cognitive Science as an Interface Between Rational and Mechanistic Explanation
Authors: Chater Nick 
Published: March 2014

AbstractCognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation—as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces.
Donors' psychological reactions to deferral following false‐positive screening test results
Authors: Delage G. , Myhal G. , Grégoire Y. , Simmons‐Coley G.‐M. 
Published: March 2014

Background and ObjectivesBeing notified of a false‐positive infectious disease marker result can cause psychological distress in blood donors. A new notification process, informing donors of the possibility of re‐entry, was compared with the previous one in which donors were indefinitely deferred to evaluate the mitigating effect on donors' psychological distress levels.Materials and MethodsTwo groups of donors, ‘deferred donors’ (DD) and ‘donors eligible for re‐entry’ (DER), completed a questionnaire involving 5‐point scales. Levels of psychological distress, attitude towards blood donation, desire to donate blood in the future and perception of notification process quality were assessed.ResultsAttitudes towards blood donation (P = 0·0276) (DD: 3·94 ± 0·11 vs. DER 4·21 ± 0·09) and perceived quality of communication (P = 0·0108) (DD: 2·72 ± 0·12 vs. DER 3·08 ± 0·10) were significantly improved with the new notification process. No significant difference was found between groups in psychological distress levels or desire to donate blood in the future.ConclusionInforming donors of the possibility of re‐entry appears to contribute to maintaining a positive predisposition towards future blood donation. It does not, however, appear to alleviate the distress felt after being notified of a false‐positive infectious disease marker result, nor does it increase willingness to give blood again in the future.
MR‐based motion correction for PET imaging using wired active MR microcoils in simultaneous PET‐MR: Phantom study
Authors: Huang Chuan , Ackerman Jerome L. , Petibon Yoann , Brady Thomas J. , El Fakhri Georges , Ouyang Jinsong 
Published: March 2014

Purpose:Artifacts caused by head motion present a major challenge in brain positron emission tomography (PET) imaging. The authors investigated the feasibility of using wired active MR microcoils to track head motion and incorporate the measured rigid motion fields into iterative PET reconstruction.Methods:Several wired active MR microcoils and a dedicated MR coil‐tracking sequence were developed. The microcoils were attached to the outer surface of an anthropomorphic18F‐filled Hoffman phantom to mimic a brain PET scan. Complex rotation/translation motion of the phantom was induced by a balloon, which was connected to a ventilator. PET list‐mode and MR tracking data were acquired simultaneously on a PET‐MR scanner. The acquired dynamic PET data were reconstructed iteratively with and without motion correction. Additionally, static phantom data were acquired and used as the gold standard.Results:Motion artifacts in PET images were effectively removed by wired active MR microcoil based motion correction. Motion correction yielded an activity concentration bias ranging from −0.6% to 3.4% as compared to a bias ranging from −25.0% to 16.6% if no motion correction was applied. The contrast recovery values were improved by 37%–156% with motion correction as compared to no motion correction. The image correlation (mean ± standard deviation) between the motion corrected (uncorrected) images of 20 independent noise realizations and static reference was R2 = 0.978 ± 0.007 (0.588 ± 0.010, respectively).Conclusions:Wired active MR microcoil based motion correction significantly improves brain PET quantitative accuracy and image contrast.
Long‐term stability and mechanical characteristics of kV digital imaging system for proton radiotherapy
Authors: Zhu Mingyao , Botticello Thomas , Lu Hsiao‐Ming , Winey Brian 
Published: March 2014

Purpose:To quantitatively evaluate the long‐term image panel positioning stability and gantry angle dependence for gantry‐mounted kV imaging systems.Methods:For patient setup digital imaging systems in isocentric rotating proton beam delivery facilities, physical crosshairs are commonly inserted into the snout to define the kV x‐ray beam isocenter. Utilizing an automatic detection algorithm, the authors analyzed the crosshair center positions in 2744 patient setup kV images acquired with the four imagers in two treatment rooms from January 2012 to January 2013. The crosshair position was used as a surrogate for imaging panel position, and its long‐term stability at the four cardinal angles and the panel flex dependency on gantry angle was investigated.Results:The standard deviation of the panel position distributions was within 0.32 mm (with the range of variation less than ± 1.4 mm) in both the X‐Z plane and Y direction. The mean panel inplane rotations were not more than 0.51° for the four panels at the cardinal angles, with standard deviations ≤0.26°. The panel position variations with gantry rotation due to gravity (flex) were within ±4 mm, and were panel‐specific.Conclusions:The authors demonstrated that the kV image panel positions in our proton treatment system were highly reproducible at the cardinal angles over 13 months and also that the panel positions can be correlated to gantry angles. This result indicates that the kV image panel positions are stable over time; the amount of panel sag is predictable during gantry rotation and the physical crosshair for kV imaging may eventually be removed, with the imaging beam isocenter position routinely verified by adequate quality assurance procedures and measurements.
Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus
Authors: O'Donnell Christopher D. , Wright Amber , Vogel Leatrice , Boonnak Kobporn , Treanor John J. , Subbarao Kanta 
Published: March 2014

ABSTRACTThe hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.
Controlled Clinical Comparison of New Pediatric Medium with Adsorbent Polymeric Beads (PF Plus) versus Charcoal-Containing PF Medium in the BacT/Alert Blood Culture System
Authors: Doern Christopher D. , Mirrett Stanley , Halstead Diane , Abid Joan , Okada Pamela , Reller L. Barth 
Published: March 2014

ABSTRACT

We conducted a controlled clinical comparison of PF Plus, the new pediatric medium with adsorbent polymeric beads, versus the charcoal-containing PF medium in the BacT/Alert blood culture system. A total of 2,381 pediatric cultures were enrolled, and 1,703 (71.5%) were deemed to be compliant and acceptable for analysis. Seventy-two cultures (4.2%) had a positive result with 80 clinically significant microorganisms. The results showed that the PF Plus medium yielded more clinically significant microorganisms than the BacT/Alert system (
P
< 0.05). In addition, the PF Plus bottle yielded positive results an average of 5.0 h earlier than the PF bottle for compliant clinically significant cultures (18.3 h versus 23.2 h,
P
= 0.004). PF Plus is an improved medium for detecting microorganisms that cause pediatric bloodstream infections.
Human Cathelicidin LL-37 Resistance and Increased Daptomycin MIC in Methicillin-Resistant Staphylococcus aureus Strain USA600 (ST45) Are Associated with Increased Mortality in a Hospital Setting
Authors: Sakoulas George , Guram Kripa , Reyes Katherine , Nizet Victor , Zervos Marcus 
Published: March 2014

ABSTRACT

Bacteremia caused by methicillin-resistant
Staphylococcus aureus
(MRSA) USA600 has been associated with increased patient mortality. We found that USA600 MRSA exhibited significantly increased resistance to human cathelicidin LL-37 killing and daptomycin MIC creep compared to non-USA600 MRSA. Virulent health care-associated MRSA strains may coevolve innate host defense peptide and antibiotic resistances.
Multilocus Sequence Typing of Serially Collected Isolates of Cryptococcus from HIV-Infected Patients in South Africa
Authors: Van Wyk Marelize , Govender Nelesh P. , Mitchell Thomas G. , Litvintseva Anastasia P. 
Published: March 2014

ABSTRACT

Patients with cryptococcal meningitis in sub-Saharan Africa frequently relapse following treatment. The natural history and etiology of these recurrent episodes warrant investigation. Here, we used multilocus sequence typing (MLST) to compare the molecular genotypes of strains of
Cryptococcus neoformans
and
Cryptococcus gattii
isolated from serial episodes of cryptococcal meningitis that were separated by at least 110 days. The most common MLST genotypes among the isolates were the dominant global clinical genotypes (M5 and M4) of molecular type VNI, as well as the VNI genotypes apparently restricted to southern Africa. In addition, there was considerable genetic diversity among these South African isolates, as 15% of the patients had unique genotypes. Eleven percent of the patients were reinfected with a genetically different strain following their initial diagnosis and treatment. However, the majority of serial episodes (89%) were caused by strains with the same genotype as the original strain. These results indicate that serial episodes of cryptococcosis in South Africa are frequently associated with persistence or relapse of the original infection. Using a reference broth microdilution method, we found that the serial isolates of 11% of the patients infected with strains of
C. neoformans
var.
grubii
with identical genotypes exhibited ≥4-fold increases in the MICs to fluconazole. Therefore, these recurrent episodes may have been precipitated by inadequate induction or consolidation of antifungal treatment and occasionally may have been due to increased resistance to fluconazole, which may have developed during the chronic infection.
Mycobacterium massiliense Bacteremia as a Consequence of M. massiliense Pneumonia in a Patient with Acute Lymphoblastic Leukemia
Authors: Kim Jaewook , Park Jeong Su , Jeong Yun Sil , Kim Dae-Young , Sung Heungsup , Kim Mi-Na 
Published: March 2014

ABSTRACT

A 52-year-old woman with relapsed acute lymphoblastic leukemia was diagnosed with
Mycobacterium massiliense
pneumonia after 4 months of chemotherapy. She developed
M. massiliense
bacteremia 1 month later. This is the first report of a proven case of
M. massiliense
bacteremia as a consequence of
M. massiliense
pneumonia.
Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses
Authors: Debbink Kari , Lindesmith Lisa C. , Ferris Martin T. , Swanstrom Jesica , Beltramello Martina , Corti Davide , Lanzavecchia Antonio , Baric Ralph S. 
Published: March 2014

ABSTRACT
Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus-like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates.

IMPORTANCE
Noroviruses are agents of gastrointestinal illness, infecting an estimated 21 million people per year in the United States alone. In healthy individuals, symptomatic infection typically resolves within 24 to 48 h. However, symptoms may persist for years in immunocompromised individuals, and development of successful treatments for these patients is a continuing challenge. This work is relevant to the design of successful norovirus therapeutics for chronically infected patients; provides support for previous assertions that chronically infected individuals may serve as reservoirs for new, antigenically unique emergent strains; and furthers our understanding of genogroup II, genotype 4 (GII.4) norovirus immune-driven molecular evolution.
Antibody-Mediated Immune Control of a Retrovirus Does Not Require the Microbiota
Authors: Wilks Jessica , Beilinson Helen , Theriault Betty , Chervonsky Alexander , Golovkina Tatyana 
Published: March 2014

ABSTRACTCommensal microbes are often required to control viral infection by facilitating host immune defenses. However, we found that this does not hold true for retroviral infection. We report that retrovirus-resistant mice control the pathogen with virus-neutralizing antibodies independently of commensal microbiota. This is in contrast to orthomyxoviruses and arenaviruses, where resistance is ablated in animals depleted of microbiota. Clearly, when it comes to antiviral immunity, the role of the microbiota cannot be generalized.
Protein Interferon-Stimulated Gene 15 Conjugation Delays but Does Not Overcome Coronavirus Proliferation in a Model of Fulminant Hepatitis
Authors: Ma Xue-Zhong , Bartczak Agata , Zhang Jianhua , He Wei , Shalev Itay , Smil David , Chen Limin , Phillips Jim , Feld Jordan J. , Selzner Nazia , Levy Gary , McGilvray Ian 
Published: March 2014

ABSTRACT

Coronaviruses express a deubiquitinating protein, the papain-like protease-2 (PLP2), that removes both ubiquitin and the ubiquitin-like interferon (IFN)-stimulated gene 15 (ISG15) protein from target proteins. ISG15 has antiviral activity against a number of viruses; therefore, we examined the effect of ISG15 conjugation (ISGylation) in a model of acute viral hepatitis induced by the murine hepatitis virus strain 3 (MHV-3) coronavirus. Mice deficient in the ISG15 deconjugating enzyme, ubiquitin-specific peptidase-18 (USP18), accumulate high levels of ISG15-conjugated proteins and are hypersensitive to type I IFN. Infecting USP18
−/−
mice with MHV-3 resulted in extended survival (8 ± 1.2 versus 4 days) and in improved liver histology, a decreased inflammatory response, and viral titers 1 to 2 logs lower than in USP18
+/+
mice. The suppression of viral replication was not due to increased IFN since infected USP18
−/−
mice had neither increased hepatic IFN-α, -β, or -γ mRNA nor circulating protein. Instead, delayed MHV-3 replication coincided with high levels of cellular ISGylation. Decreasing ISGylation by knockdown of the ISG15 E1 enzyme, Ube1L, in primary USP18
+/+
and USP18
−/−
hepatocytes led to increased MHV-3 replication. Both
in vitro
and
in vivo
, increasing MHV-3 titers were coincident with increased PLP2 mRNA and decreased ISGylation over the course of infection. The pharmacologic inhibition of the PLP2 enzyme
in vitro
led to decreased MHV-3 replication. Overall, these results demonstrate the antiviral effect of ISGylation in an
in vivo
model of coronavirus-induced mouse hepatitis and illustrate that PLP2 manipulates the host innate immune response through the ISG15/USP18 pathway.

IMPORTANCE
There have been a number of serious worldwide pandemics due to widespread infections by coronavirus. This virus (in its many forms) is difficult to treat, in part because it is very good at finding “holes” in the way that the host (the infected individual) tries to control and eliminate the virus. In this study, we demonstrate that an important host viral defense—the ISG15 pathway—is only partially effective in controlling severe coronavirus infection. Activation of the pathway is very good at suppressing viral production, but over time the virus overwhelms the host response and the effects of the ISG15 pathway. These data provide insight into host-virus interactions during coronavirus infection and suggest that the ISG15 pathway is a reasonable target for controlling severe coronavirus infection although the best treatment will likely involve multiple pathways and targets.