bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cord blood banking and transplantation
Authors: Hwang W. Y. K. 
Published: October 2011

The availability of umbilical cord blood (UCB) as a source of haematopoietic stem cells (HSC) for transplantation has met an important niche in the field of HSC transplantation (HSCT) as patients unable to find a HLA‐matched sibling or unrelated donor have been able to receive less well‐matched UCB transplantation (UCBT) with equivalent outcomes. This has led to significant growth in this field resulting in more than 20 000 unrelated donor UCBTs performed to date with about 3000 more performed annually. Growth of UCBT has been further supported by the proliferation of public cord blood banks throughout the world which store UCB at no cost to the donor, making these available for patients all round the world through global search registries like the US National Marrow Donor Program (NMDP), NetCord and the Bone Marrow Donors Worldwide (BMDW). International organizations like the World Marrow Donor Association have also helped to steer these efforts through the formulation and distribution of guidelines and protocols for these cord blood banks and bone marrow registries. The US Food and Drug Administration (FDA) has also stepped in to regulate publicly banked UCB as an Investigational New Drug (IND).The key limiting factor in UCBT is in the limited number of cells for transplantation (about 10‐fold less than donated bone marrow) resulting in delayed engraftment and even non‐engraftment, particularly for adult patients for whom UCB cell doses may be insufficient relative to the patient’s body size. Efforts to overcome this barrier include the use of concurrent infusion of two differing cord blood units in order to raise the cumulative cell dose. Interestingly, this does not lead to mutual rejection of the CBUs, but appears to result in an additive effect on enhancing engraftment. Other efforts to overcome cell dose constraints of cord blood include direct bone marrow injection, use of homing molecules and ex vivo cord blood expansion.Cell dose is also an important consideration for cord blood banking as donated UCB that is collected with cell count <800 million nucleated cells has very low chance of utilization by many transplant centres which demand the best cell doses for their patients. As such, not all UCB collected is banked, although many of the low volume cords can still be reassigned to research. Strategies to increase the number of cells collected from each delivery include the use of ex utero devices which apply suction, perfusion or pressure to delivered placenta and umbilical cord in order to maximize HSC collection. Devices which enhance cell recovery during cord blood processing also help to minimize cell loss. Other strategies which might influence obstetric practice are not advised.As the worldwide experience in UCBT and UCB banking grows, patient outcomes have continued to improve such that UCBT now has a firm place in the HSCT spectrum of care with even greater potential for growth in the years to come. The challenge is for these advances to stay cost‐effective so that the majority of patients can still have access to them.
Molecular genetic basis for I antigen expression
Authors: Yu L.‐C. , Lin M. 
Published: October 2011

The rapid conversion of the i to the I phenotype on postnatal red blood cells (RBCs) reflects the elaborate functions of cell surface branched‐chain I antigenic structure. The adult i phenotype has been noted to be partially associated with congenital cataracts. These phenomena make the molecular genetics of the blood group I system and the regulation mechanism for I antigen expression in postnatal RBCs intriguing. It has been demonstrated that the human I locus expresses three IGnT forms, designated IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exons 2 and 3, coding regions. The uncommon molecular genetics of the I locus offers a new perspective of the formation and expression of the I antigen in different cells, and provides an insight into the questions derived from investigation of the adult i phenotype. The results obtained from molecular analysis of two adult i groups, with and without congenital cataracts, support the proposed molecular mechanism for the partial association of the two traits, namely that mutations that lead to the production of mutant IGnTC only, may result in an adult i phenotype but not congenital cataracts, whereas mutation events that occur in the common exon 2 or exon 3 regions, which result in the elimination of the activity of all three IGnT enzymes, would seem to lead to the development of both traits. This suggests that an I‐gene defect may lead directly to the development of congenital cataracts. However, the result of the gene knock‐out mouse model does not confirm this suggestion.Analysis of the regulation for I antigen expression shows that i‐to‐I phenotypic transition during erythroid differentiation is regulated by the transcription factor CCAAT/enhancer binding protein α (C/EBPα), which enhances transcription of the IGnTC gene, consequently leading to the formation of the cell surface I antigen. Subsequent investigation further showed that phosphorylation of the Ser‐21 residue on C/EBPα blocks C/EBPα activity on IGnTC gene induction, while dephosphorylation of C/EBPα Ser‐21 occurs in both the granulopoietic and erythropoietic processes, leading to stimulation of IGnTC gene expression and consequently I antigen formation. These results demonstrate that the formation of I antigen during the development of erythrocytes, and also granulocytes, is determined by a mechanism that is known to be crucial to determining granulopoiesis, namely involvement of the transcription factor C/EBPα and Ser‐21 dephosphorylation of this protein.
Scatter correction for full‐fan volumetric CT using a stationary beam blocker in a single full scan
Authors: Niu Tianye , Zhu Lei 
Published: October 2011

Purpose:Applications of volumetric CT (VCT) are hampered by shading and streaking artifacts in the reconstructed images. These artifacts are mainly due to strong x‐ray scatter signals accompanied with the large illumination area within one projection, which lead to CT number inaccuracy, image contrast loss and spatial nonuniformity. Although different scatter correction algorithms have been proposed in literature, a standard solution still remains unclear. Measurement‐based methods use a beam blocker to acquire scatter samples. These techniques have unrivaled advantages over other existing algorithms in that they are simple and efficient, and achieve high scatter estimation accuracy without prior knowledge of the imaged object. Nevertheless, primary signal loss is inevitable in the scatter measurement, and multiple scans or moving the beam blocker during data acquisition are typically employed to compensate for the missing primary data. In this paper, we propose a new measurement‐based scatter correction algorithm without primary compensation for full‐fan VCT. An accurate reconstruction is obtained with one single‐scan and a stationary x‐ray beam blocker, two seemingly incompatible features which enable simple and efficient scatter correction without increase of scan time or patient dose.Methods:Based on the CT reconstruction theory, we distribute the blocked data over the projection area where primary signals are considered approximately redundant in a full scan, such that the CT image quality is not degraded even with primary loss. Scatter is then accurately estimated by interpolation and scatter‐corrected CT images are obtained using an FDK‐based reconstruction algorithm.Results:The proposed method is evaluated using two phantom studies on a tabletop CBCT system. On the Catphan©600 phantom, our approach reduces the reconstruction error from 207 Hounsfield unit (HU) to 9 HU in the selected region of interest, and improves the image contrast by a factor of 2.0 in the high‐contrast regions. On an anthropomorphic head phantom, the reconstruction error is reduced from 97 HU to 6 HU in the soft tissue region and image spatial nonuniformity decreases from 27% to 5% after correction.Conclusions:Our method inherits the main advantages of measurement‐based methods while avoiding their shortcomings. It has the potential to become a practical scatter correction solution widely implementable on different VCT systems.
Serological Prevalence of Helicobacter pylori Infection in Saxony-Anhalt, Germany, in 2010
Authors: Wex Thomas , Venerito Marino , Kreutzer Juliane , Götze Tobias , Kandulski Arne , Malfertheiner Peter 
Published: October 2011

ABSTRACT

Epidemiological studies from different countries have shown a steady decline of the prevalence of
Helicobacter pylori
infection. In order to investigate the current seroprevalence of
H. pylori
infection in the area of Magdeburg, a city of the former East Germany,
H. pylori
antibodies of patients presenting in our emergency wards were analyzed. In total, 2,318 patients (1,181 males and 1,137 females) enrolled between September 2009 and August 2010 were tested for immunoglobulin G (IgG) against
H. pylori
and anti-CagA antibodies by specific enzyme immunoassay (EIA). Patients with either anti-
H. pylori
IgG or anti-CagA antibodies were classified as
H. pylori
positive, whereas the lack of both antibodies led to the assignment of an
H. pylori-
negative status. The overall seroprevalence of
H. pylori
infection was 44.4% (
n
= 1,029 out of 2,318) and did not differ in relation to sex. The proportion of CagA-positive samples was 43.3% of all
H. pylori
-positive individuals (446 out of 1,029). The seroprevalence showed a birth cohort effect (0 to 20 years of age, 14.6%; 21 to 30 years, 22.4%; 31 to 40 years, 40.6%; 41 to 50 years, 45.5%; 51 to 60 years, 50.8%) up to the age of 60, while it remained between 40.7% and 50.5% for the following decades. Patients younger than 30 years were significantly less
H. pylori
positive (21.1%) than those older than 30 years of age (47.7%;
P
< 0.01), whereas CagA status was similar (44.3 versus 43.3%). Notably, young women (<30 years old) had significantly higher CagA positivity (59.3%) than corresponding men (32.5%;
P
= 0.016). Taken together, seroprevalence of
H. pylori
infection shows a significant drop in subjects born after 1980 in Saxony-Anhalt but still remains in the range of 40 to 50% in subjects born earlier.
PCR Diagnosis of Pneumocystis Pneumonia: a Bivariate Meta-Analysis
Authors: Lu Yuan , Ling Guoya , Qiang Chenyi , Ming Qinshou , Wu Cong , Wang Ke , Ying Zouxiao 
Published: October 2011

ABSTRACT

We undertook a bivariate meta-analysis to assess the overall accuracy of respiratory specimen PCR assays for diagnosing
Pneumocystis
pneumonia. The summary sensitivity and specificity were 0.99 (95% confidence interval, 0.96 to 1.00) and 0.90 (0.87 to 0.93). Subgroup analyses showed that quantitative PCR analysis and the major surface glycoprotein gene target had the highest specificity value (0.93). Respiratory specimen PCR results are sufficient to confirm or exclude the disease for at-risk patients suspected of having
Pneumocystis
pneumonia.
Defining the Roles of
cis
-Acting RNA Elements in Tombusvirus Replicase Assembly
In Vitro
Authors: Pathak Kunj B. , Pogany Judit , Xu Kai , White K. Andrew , Nagy Peter D. 
Published: October 2011

ABSTRACT

In addition to its central role as a template for replication and translation, the viral plus-strand RNA genome also has nontemplate functions, such as recruitment to the site of replication and assembly of the viral replicase, activities that are mediated by
cis
-acting RNA elements within viral genomes. Two noncontiguous RNA elements, RII(+)-SL (located internally in the tombusvirus genome) and RIV (located at the 3′-terminus), are involved in template recruitment into replication and replicase assembly; however, the importance of each of these RNA elements for these two distinct functions is not fully elucidated. We used an
in vitro
replicase assembly assay based on yeast cell extract and purified recombinant tombusvirus replication proteins to show that RII(+)-SL, in addition to its known requirement for recruitment of the plus-strand RNA into replication, is also necessary for assembly of an active viral replicase complex. Additional studies using a novel two-component RNA system revealed that the recruitment function of RII(+)-SL can be provided in
trans
by a separate RNA and that the replication silencer element, located within RIV, defines the template that is used for initiation of minus-strand synthesis. Collectively, this work has revealed new functions for tombusvirus
cis
-acting RNA elements and provided insights into the pioneering round of minus-strand synthesis.
p53 Degradation Activity, Expression, and Subcellular Localization of E6 Proteins from 29 Human Papillomavirus Genotypes
Authors: Mesplède Thibault , Gagnon David , Bergeron-Labrecque Fanny , Azar Ibrahim , Sénéchal Hélène , Coutlée François , Archambault Jacques 
Published: October 2011

ABSTRACT

Human papillomaviruses (HPVs) are the etiological agents of cervical cancer and other human malignancies. HPVs are classified into high- and low-risk genotypes according to their association with cancer. Host cell transformation by high-risk HPVs relies in part on the ability of the viral E6 protein to induce the degradation of p53. We report the development of a cellular assay that accurately quantifies the p53 degradation activity of E6
in vivo
, based on the fusion of p53 to
Renilla
luciferase (RLuc-p53). This assay was used to measure the p53 degradation activities of E6 proteins from 29 prevalent HPV types and variants of HPV type 16 (HPV16) and HPV33 by determining the amount of E6 expression vector required to reduce by half the levels of RLuc-p53 (50% effective concentration [EC
50
]). These studies revealed an unexpected variability in the p53 degradation activities of different E6 proteins, even among active types whose EC
50
s span more than 2 log units. Differences in activity were greater between types than between variants and did not correlate with differences in the intracellular localization of E6, with most being predominantly nuclear. Protein and mRNA expression of the 29 E6 proteins was also examined. For 16 high-risk types, spliced transcripts that encode shorter E6*I proteins of variable sizes and abundances were detected. Mutation of the splice donor site in five different E6 proteins increased their p53 degradation activity, suggesting that mRNA splicing can limit the activity of some high-risk E6 types. The quantification of p53 degradation
in vivo
represents a novel tool to systematically compare the oncogenic potentials of E6 proteins from different HPV types and variants.
Epstein-Barr Virus Isolates Retain Their Capacity To Evade T Cell Immunity through BNLF2a despite Extensive Sequence Variation
Authors: Horst Daniëlle , Burrows Scott R. , Gatherer Derek , van Wilgenburg Bonnie , Bell Melissa J. , Boer Ingrid G. J. , Ressing Maaike E. , Wiertz Emmanuel J. H. J. 
Published: October 2011

ABSTRACT

The Epstein-Barr virus (EBV)-encoded immune evasion protein BNLF2a inhibits the
t
ransporter associated with
a
ntigen
p
rocessing (TAP), thereby downregulating HLA class I expression at the cell surface. As a consequence, recognition of EBV-infected cells by cytotoxic T cells is impaired. Here, we show that sequence polymorphism of the BNLF2a protein is observed with natural EBV isolates, with evidence for positive selection. Despite these mutations, the BNLF2a variants efficiently reduce cell surface HLA class I levels. This conservation of BNLF2a function during evolution of EBV implies an important role for the viral TAP inhibitor in preventing T cell recognition during viral infection.
Evolutionary Dynamics of Local Pandemic H1N1/2009 Influenza Virus Lineages Revealed by Whole-Genome Analysis
Authors: Baillie Gregory J. , Galiano Monica , Agapow Paul-Michael , Myers Richard , Chiam Rachael , Gall Astrid , Palser Anne L. , Watson Simon J. , Hedge Jessica , Underwood Anthony , Platt Steven , McLean Estelle , Pebody Richard G. , Rambaut Andrew , Green Jonathan , Daniels Rod , Pybus Oliver G. , Kellam Paul , Zambon Maria 
Published: October 2011

ABSTRACT
Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.
Stimulation of the Human RAD51 Nucleofilament Restricts HIV-1 Integration
In Vitro
and in Infected Cells
Authors: Cosnefroy O. , Tocco A. , Lesbats P. , Thierry S. , Calmels C. , Wiktorowicz T. , Reigadas S. , Kwon Y. , De Cian A. , Desfarges S. , Bonot P. , San Filippo J. , Litvak S. , Le Cam E. , Rethwilm A. , Fleury H. , Connell P. P. , Sung P. , Delelis O. , Andréola M. L. , Parissi V. 
Published: October 2011

ABSTRACT

Stable HIV-1 replication requires the DNA repair of the integration locus catalyzed by cellular factors. The human RAD51 (hRAD51) protein plays a major role in homologous recombination (HR) DNA repair and was previously shown to interact with HIV-1 integrase (IN) and inhibit its activity. Here we determined the molecular mechanism of inhibition of IN. Our standard
in vitro
integration assays performed under various conditions promoting or inhibiting hRAD51 activity demonstrated that the formation of an active hRAD51 nucleofilament is required for optimal inhibition involving an IN-DNA complex dissociation mechanism. Furthermore we show that this inhibition mechanism can be promoted in HIV-1-infected cells by chemical stimulation of the endogenous hRAD51 protein. This hRAD51 stimulation induced both an enhancement of the endogenous DNA repair process and the inhibition of the integration step. Elucidation of this molecular mechanism leading to the restriction of viral proliferation paves the way to a new concept of antiretroviral therapy based on the enhancement of endogenous hRAD51 recombination activity and highlights the functional interaction between HIV-1 IN and hRAD51.
Conditional CD8+T Cell Escape during Acute Simian Immunodeficiency Virus Infection
Authors: O'Connor Shelby L. , Becker Ericka A. , Weinfurter Jason T. , Chin Emily N. , Budde Melisa L. , Gostick Emma , Correll Michael , Gleicher Michael , Hughes Austin L. , Price David A. , Friedrich Thomas C. , O'Connor David H. 
Published: October 2011

ABSTRACTCD8+T cell responses rapidly select viral variants during acute human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. We used pyrosequencing to examine variation within three SIV-derived epitopes (Gag386-394GW9, Nef103-111RM9, and Rev59-68SP10) targeted by immunodominant CD8+T cell responses in acutely infected Mauritian cynomolgus macaques. In animals recognizing all three epitopes, variation within Rev59-68SP10 was associated with delayed accumulation of variants in Gag386-394GW9 but had no effect on variation within Nef103-111RM9. This demonstrates that the entire T cell repertoire, rather than a single T cell population, influences the timing of immune escape, thereby providing the first example of conditional CD8+T cell escape in HIV/SIV infection.
Fatal Pancreatitis in Simian Immunodeficiency Virus SIV
mac251
-Infected Macaques Treated with 2′,3′-Dideoxyinosine and Stavudine following Cytotoxic-T-Lymphocyte-Associated Antigen 4 and Indoleamine 2,3-Dioxygenase Blockade
Authors: Vaccari Monica , Boasso Adriano , Fenizia Claudio , Fuchs Dietmar , Hryniewicz Anna , Morgan Tia , Weiss Deborah , Doster Melvin N. , Heraud Jean Michel , Shearer Gene M. , Franchini Genoveffa 
Published: October 2011

ABSTRACT

Human immunodeficiency virus (HIV) infection is associated with immune activation, CD4
+
-T-cell loss, and a progressive decline of immune functions. Antiretroviral therapy (ART) only partially reverses HIV-associated immune dysfunction, suggesting that approaches that target immune activation and improve virus-specific immune responses may be needed. We performed a preclinical study in rhesus macaques infected with the pathogenic simian immunodeficiency virus SIV
mac251
and treated with ART. We tested whether vaccination administered together with cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) blockade and treatment with the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-
d
-tryptophan (
d
-1mT), decreased immune activation and improved vaccine efficacy. The treatment did not augment vaccine immunogenicity; rather, it dramatically increased ART-related toxicity, causing all treated animals to succumb to acute pancreatitis and hyperglycemic coma. The onset of fulminant diabetes was associated with severe lymphocyte infiltration of the pancreas and complete loss of the islets of Langerhans. Thus, caution should be used when considering approaches aimed at targeting immune activation during ART.
Adeno-Associated Virus Type 2 Modulates the Host DNA Damage Response Induced by Herpes Simplex Virus 1 during Coinfection
Authors: Vogel Rebecca , Seyffert Michael , Strasser Regina , de Oliveira Anna P. , Dresch Christiane , Glauser Daniel L. , Jolinon Nelly , Salvetti Anna , Weitzman Matthew D. , Ackermann Mathias , Fraefel Cornel 
Published: October 2011

ABSTRACT
Adeno-associated virus type 2 (AAV2) is a human parvovirus that relies on a helper virus for efficient replication. Herpes simplex virus 1 (HSV-1) supplies helper functions and changes the environment of the cell to promote AAV2 replication. In this study, we examined the accumulation of cellular replication and repair proteins at viral replication compartments (RCs) and the influence of replicating AAV2 on HSV-1-induced DNA damage responses (DDR). We observed that the ATM kinase was activated in cells coinfected with AAV2 and HSV-1. We also found that phosphorylated ATR kinase and its cofactor ATR-interacting protein were recruited into AAV2 RCs, but ATR signaling was not activated. DNA-PKcs, another main kinase in the DDR, was degraded during HSV-1 infection in an ICP0-dependent manner, and this degradation was markedly delayed during AAV2 coinfection. Furthermore, we detected phosphorylation of DNA-PKcs during AAV2 but not HSV-1 replication. The AAV2-mediated delay in DNA-PKcs degradation affected signaling through downstream substrates. Overall, our results demonstrate that coinfection with HSV-1 and AAV2 provokes a cellular DDR which is distinct from that induced by HSV-1 alone.