bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Sanger Mouse Genetics Programme: High Throughput Characterisation of Knockout Mice
Authors: GARDIN A , WHITE J 
Published: December 2011

AbstractPurpose The Sanger Mouse Genetics Project (MGP) is committed to making a significant contribution to the functional annotation of the mammalian genome by generating, characterising and archiving in the order of 200 lines of knockout mice per year, including 125 lines which have been processed as part of the EUMODIC consortium. Phenotypic data on a spectrum of disease conditions are obtained for each mouse line without the need for any prior assumptions about function by performing a standardised battery of phenotyping screens. The data generated will help to further the understanding of the interplay of genes and disease and provide an insight into the various underlying biological pathways. All phenotyping data and biological resources generated by the project are openly available to the scientific community.Methods Eye morphology is routinely assessed using a standard parameter assessment list in conjunction with the Slit Lamp and Ophthalmoscope and images are collected when abnormalities are identified. Expression profiling via the lacZ reporter gene is performed for each mutant line in adults and at E14.5. We collaborate with University of Iowa who are performing a pathology review of H&E stained paraffin sections and also sectioning of lacZ positive eyes.Results To date, the eye screen has been completed on over 310 mutant lines. Here we report examples of novel eye‐related abnormalities identified by the eye morphology, embryonic lethality and/or expression screens performed by the Sanger MGP. We will present how to identify a potentially interesting mouse mutant on our database and discuss the impact our knockout mouse models might have on your research.
Colour vision in adult amblyopia
Authors: BLACK JM , LUN V , PHILLIPS G , THOMPSON B 
Published: December 2011

AbstractPurpose Amblyopia is a disorder of visual processing. There is evidence that the parvocellular pathway, which prefers chromatic stimuli, is selectively damaged in amblyopia. Consistent with this hypothesis, previous studies have demonstrated that patients with amblyopia show poorer performance on colour vision tests.Methods Ten adult amblyopic subjects (3 strabismic, 5 anisometropic and 3 mixed) were tested using the Farnsworth Munsell 100 Hue (FM100Hue)colour vision test. In separate testing sessions, positive spherical lenses were used to induce blur in the fellow eye (FFE)to match the near acuity of the amblyopic eye (AME). The test (all boxes)was performed under five conditions(randomised): AME,FFE,binocularly (BIN),FFE with blur and BIN with the FFE blurred. Age matched controls were included to assess the effect of defocus in normal subjects, with blur placed in front of the non‐dominant eye to induce mild, moderate or severe blur.Results Amblyopic participants performed well in the FM100Hue test, with scores falling within normal age means in 9/11 subjects (in the AME). Strabismic amblyopes had a more pronounced deficit in error scores. Across all amblyopic subjects, performance was significantly beter under BIN conditions (p=0.023). Induced blur in controls only affected error scores under the severe blur condition, and had litle effect in amblyopic participants.Conclusion This study has shown that amblyopes perform well in this commonly performed colour vision test, and demonstrated improved test performance under binocular conditions. The low spatial frequency of the stimuli may allow for extensive pooling of chromatic information therefore allowing performance of this test to be robust to a parvocellular dysfunction.
Gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation
Authors: Wook Hwang Seong , Jae Lee Sun , Eun Park Po , Seon Kim Mee , Bae Han‐Ik 
Published: December 2011

ABSTRACTWe report a patient with gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation. A 67‐year‐old man visited our hospital for further evaluations due to gastric adenocarcinoma. The gastric cancer was located in the prepyloric area and appeared to be a protruding mass with an infiltrative growth pattern. Initial pancreatic and postoperative hepatic and pulmonary metastases were detected radiologically. Microscopically, choriocarcinomatous and hepatoid differentiation was observed with a moderately differentiated adenocarcinoma. The choriocarcinomatous components were positive for β‐hCG and the hepatoid components were positive for α‐fetoprotein (AFP). These uncommon pathological patterns are supposed to arise from the retrodifferentiation pathway of primary gastric adenocarcinoma. The preoperative laboratory data revealed elevated serum AFP (773.4 ng/mL) and carcinoembryonic antigen (62.2 ng/mL), whereas other tests were unremarkable. The prognosis of gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation is very poor; our patient died 4 months after the operation.
Comparison of HIV-1 RNA Measurements Obtained by Using Plasma and Dried Blood Spots in the Automated Abbott Real-Time Viral Load Assay
Authors: Arredondo Miguel , Garrido Carolina , Parkin Neil , Zahonero Natalia , Bertagnolio Silvia , Soriano Vincent , de Mendoza Carmen 
Published: December 2011

ABSTRACTDried blood spots (DBS) may be a promising alternative specimen type to plasma for measuring the viral load (VL) in HIV-infected individuals in resource-limited settings. However, characterization of assay performance using DBS is incomplete. In this prospective study, the VL was measured in parallel using plasma and DBS specimens collected at the same time from 157 HIV-1-infected individuals. DBS were prepared by dispensing 50 μl of blood onto filter paper cards and were stored desiccated at −20°C. Nucleic acid extraction from plasma and DBS was performed automatically using the Abbott m2000sp instrument, and the VL was measured using the RealTime HIV-1 VL assay, which has a lower limit of detection of 40 HIV RNA copies/ml. The correlation between plasma and DBS results was good (R= 0.91;P< 0.001). The mean difference in the VL (DBS minus plasma) was 0.35 log copies (standard deviation [SD], 0.47 log copies). A total of 40 (26%) paired specimens had a difference of >0.5 log copy, and in 12 (7.8%) it was >1 log copy. the VL from DBS was measurable in 95.7% of specimens with a plasma VL of >2.74 log copies (550 HIV RNA copies/ml). In summary, the VL can reliably be measured using DBS with the Abbott RealTime HIV-1 assay. The estimated lower limit of detection of this automated methodology on DBS is 550 copies/ml, a threshold that may be acceptable for periodic VL monitoring in patients on antiretroviral therapy in resource-limited settings, where early detection of virologic treatment failure is often problematic.
Evaluation of a Recombinant Antigen-Based Enzyme Immunoassay for the Diagnosis of Noninvasive Aspergillosis
Authors: Guitard J. , Sendid B. , Thorez S. , Gits M. , Hennequin C. 
Published: December 2011

ABSTRACT

Antibody detection is a key diagnostic tool for noninvasive aspergillosis (NIA) such as allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Specific immunoprecipitin detection (IPD) is considered as the reference but lacks standardization and is time-consuming. To evaluate the performance of a new anti-
Aspergillus fumigatus
IgG enzyme immunoassay (EIA) kit using a recombinant
A. fumigatus
antigen (Bio-Rad), a retrospective study was performed on 551 sera collected from patients with a definite diagnosis of NIA (group 1;
n
= 64), bronchial
Aspergillus
colonization (group 2;
n
= 26), and probable aerial
Aspergillus
contamination (group 3;
n
= 44); from patients suspected of NIA with negative serological and mycological investigations (group 4;
n
= 49); and from a group of 222 patients not suspected of NIA (group 5). The EIA exhibited excellent reproducibility with coefficients of variation below 10%. Agreement with IPD was calculated between 62.5 and 84.4% according to the group of patients with Cohen's kappa coefficient at 0.6196 ± 0.077. Taking as reference a composite status including clinical, radiological, mycological, and serological data, sensitivity (group 1) and specificity (other groups) were calculated between 90.2 and 93.8% and 54.3 and 100%, respectively. Lower specificity was observed for patients with
Aspergillus
colonization. However, Yule
Q
coefficients estimating the correlation between EIA result and the definite diagnosis of NIA were calculated between 0.97 and 0.98. The method is a highly useful screening tool for the diagnosis of NIA, reducing the need for confirmatory IPD tests.
Molecular Characteristics of Rifampin- and Isoniazid-Resistant Mycobacterium tuberculosis Strains Isolated in Vietnam
Authors: Minh Nghiem Ngoc , Van Bac Nguyen , Son Nguyen Thai , Lien Vu Thi Kim , Ha Chu Hoang , Cuong Nguyen Huu , Mai Cung Thi Ngoc , Le Thanh Hoa 
Published: December 2011

ABSTRACT

Molecular characterization of the drug resistance of
Mycobacterium tuberculosis
strains with different origins can generate information that is useful for developing molecular methods. These methods are widely applicable for rapid detection of drug resistance. A total of 166 rifampin (RIF)- and/or isoniazid (INH)-resistant strains of
M. tuberculosis
have been isolated from different parts of Vietnam; they were screened for mutations associated with resistance to these drugs by sequence analysis investigating genetic mutations associated with RIF and INH resistance. Seventeen different mutations were identified in 74 RIF-resistant strains, 56 of which (approximately 76%) had mutations in the so-called 81-bp “hot-spot” region of the
rpoB
gene. The most common point mutations were in codons 531 (37.8%), 526 (23%), and 516 (9.46%) of the
rpoB
gene. Mutations were not found in three strains (4.05%). In the case of INH resistance, five different mutations in the
katG
genes of 82 resistant strains were detected, among which the nucleotide substitution at codon 315 (76.83%) is the most common mutation. This study provided the first molecular characterization of INH and RIF resistance of
M. tuberculosis
strains from Vietnam, and detection of the
katG
and
rpoB
mutations of the INH and RIF-resistant strains should be useful for rapid detection of the INH- and RIF-resistant strains by molecular tests.
Real-Time PCR and High-Resolution Melt Analysis for Rapid Detection of Mycobacterium leprae Drug Resistance Mutations and Strain Types
Authors: Li Wei , Matsuoka Masanori , Kai Masanori , Thapa Pratibha , Khadge Saraswoti , Hagge Deanna A. , Brennan Patrick J. , Vissa Varalakshmi 
Published: December 2011

ABSTRACTDrug resistance surveillance and strain typing ofMycobacterium lepraeare necessary to investigate ongoing transmission of leprosy in regions of endemicity. To enable wider implementation of these molecular analyses, novel real-time PCR–high-resolution melt (RT-PCR-HRM) assays without allele-specific primers or probes and post-PCR sample handling were developed. For the detection of mutations within drug resistance-determining regions (DRDRs) offolP1,rpoB, andgyrA, targets for dapsone, rifampin, and fluoroquinolones, real-time PCR-HRM assays were developed. Wild-type and drug-resistant mouse footpad-derived strains that included threefolP1, tworpoB, and onegyrAmutation types in a reference panel were tested. RT-PCR-HRM correctly distinguished the wild type from the mutant strains. In addition, RT-PCR-HRM analyses aided in recognizing samples with mixed or minor alleles and also a mislabeled sample. When tested in 121 sequence-characterized clinical strains, HRM identified all thefolP1mutants representing two mutation types, including one not within the reference panel. The false positives (<5%) could be attributed to low DNA concentration or PCR inhibition. A second set of RT-PCR-HRM assays for identification of three previously reported single nucleotide polymorphisms (SNPs) that have been used for strain typing were developed and validated in 22 reference and 25 clinical strains. Real-time PCR-HRM is a sensitive, simple, rapid, and high-throughput tool for routine screening known DRDR mutants in new and relapsed cases, SNP typing, and detection of minor mutant alleles in the wild-type background at lower costs than current methods and with the potential for quality control in leprosy investigations.
Clinical and Microbiological Features of a Cystic Fibrosis Patient Chronically Colonized with Pandoraea sputorum Identified by Combining 16S rRNA Sequencing and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Fernández-Olmos A. , Morosini M. I. , Lamas A. , García-Castillo M. , García-García L. , Cantón R. , Máiz L. 
Published: December 2011

ABSTRACT

Clonal isolates identified as various nonfermentative Gram-negative bacilli over a 5-year period from sputum cultures of a 30-year-old cystic fibrosis patient were successfully reidentified as
Pandoraea sputorum
by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Decreased lung function improved after 1 year of azithromycin and inhaled 7%-hypertonic saline treatment.
First Reports of Human Rotavirus G8P[4] Gastroenteritis in the United States
Authors: Weinberg Geoffrey A. , Payne Daniel C. , Teel Elizabeth N. , Mijatovic-Rustempasic Slavica , Bowen Michael D. , Wikswo Mary , Gentsch Jon R. , Parashar Umesh D. 
Published: December 2011

ABSTRACT
In 2009, three children were hospitalized in Rochester, NY, with sequence-confirmed G8P[4] rotavirus gastroenteritis—the first U.S. detection of this uncommon strain more typically found in Africa. Continued monitoring of G8P[4] and other rotavirus genotypes not represented in current vaccines is essential to assess whether vaccination will result in an increase in prevalence of these strains.
A New Real-Time PCR Assay for Improved Detection of the Parasite Babesia microti
Authors: Teal Allen E. , Habura Andrea , Ennis Jill , Keithly Janet S. , Madison-Antenucci Susan 
Published: December 2011

ABSTRACT

Babesiosis is an emerging zoonosis with important public health implications, as the incidence of the disease has risen dramatically over the past decade. Because the current gold standard for detection of
Babesia
is microscopic examination of blood smears, accurate identification requires trained personnel. Species in the genus cannot be distinguished microscopically, and
Babesia
can also be confused with the early trophozoite stage (ring forms) of
Plasmodium
parasites. To allow more accurate diagnosis in a format that is accessible to a wider variety of laboratories, we developed a real-time PCR assay targeting the 18S rRNA gene of
Babesia microti
, the dominant babesiosis pathogen in the United States. The real-time PCR is performed on DNA extracted from whole-blood specimens and detects
Babesia microti
with a limit of detection of ∼100 gene copies in 5 μl of blood. The real-time PCR assay was shown to be 100% specific when tested against a panel of 24 organisms consisting of
Babesia microti
, other
Babesia
species,
Plasmodium
species, tick-borne and other pathogenic bacteria, and other blood-borne parasites. The results using clinical specimens show that the assay can detect infections of lower parasitemia than can be detected by microscopic examination. This method is therefore a rapid, sensitive, and accurate method for detection of
Babesia microti
in patient specimens.
Human Papillomavirus Type-Specific Prevalence in Women with Cervical Intraepithelial Neoplasm in Western China
Authors: Li Jinke , Mei Jie , Wang Xuedong , Hu Lina , Lin Yong , Yang Pei 
Published: December 2011

ABSTRACT
Human papillomavirus (HPV) type-specific prevalence was studied in 600 cases of cervical intraepithelial neoplasm in western China by GenoArray test. HPV-16 and -58 were the most prevalent types, with prevalences of 37.8% and 21.8%, respectively. HPV-18 and -45 were uncommon types. The results show different type distributions from that of other regions, which is important evidence for the selection of future genotypes in HPV vaccines in western China.
Declining Incidence of Candidemia in a Tertiary Inpatient Pediatric Population
Authors: Ota Kaede V. , McGowan Karin L. 
Published: December 2011

ABSTRACT

We examined the incidence of candidemia,
Candida
species distribution, and antifungal susceptibility patterns in a pediatric institution. We identified 301 episodes of candidemia from 2001 to 2010 inclusive. Annual incidence decreased from 0.68 to 0.12 cases/1,000 patient days between 2004 and 2010.
Candida albicans
was the most common species, followed by
C. parapsilosis
. All isolates tested were susceptible to amphotericin B and caspofungin, but 11% were resistant or dose-dependently susceptible to fluconazole.
Productive Replication and Evolution of HIV-1 in Ferret Cells
Authors: Fadel Hind J. , Saenz Dyana T. , Guevara Rebekah , von Messling Veronika , Peretz Mary , Poeschla Eric M. 
Published: December 2011

ABSTRACT

A rodent or other small animal model for HIV-1 has not been forthcoming, with the principal obstacles being species-specific restriction mechanisms and deficits in HIV-1 dependency factors. Some Carnivorans may harbor comparatively fewer impediments. For example, in contrast to mice, the domestic cat genome encodes essential nonreceptor HIV-1 dependency factors. All Feliformia species and at least one Caniformia species also lack a major lentiviral restriction mechanism (TRIM5α/TRIMCyp proteins). Here we investigated cells from two species in another carnivore family, the Mustelidae, for permissiveness to the HIV-1 life cycle.
Mustela putorius furo
(domesticated ferret) primary cells and cell lines did not restrict HIV-1, feline immunodeficiency virus (FIV), equine infectious anemia virus (EIAV), or N-tropic murine leukemia virus (MLV) postentry and supported late HIV-1 life cycle steps comparably to human cells. The ferret TRIM5α gene exon 8, which encodes the B30.2 domain, was found to be pseudogenized. Strikingly, ferret (but not mink) cells engineered to express human HIV-1 entry receptors supported productive spreading replication, amplification, and serial passage of wild-type HIV-1. Nevertheless, produced virions had relatively reduced infectivity and the virus accrued G→A hypermutations, consistent with APOBEC3 protein pressure. Ferret cell-passaged HIV-1 also evolved amino acid changes in the capsid cyclophilin A binding loop. We conclude that the genome of this carnivore can provide essential nonreceptor HIV-1 dependency factors and that ferret APOBEC3 proteins with activity against HIV-1 are likely. Even so, unlike in cat cells, HIV-1 can replicate in ferret cells without
vif
substitution. The virus evolves in this novel nonprimate cell adaptive landscape. We suggest that further characterization of HIV-1 adaptation in ferret cells and delineation of Mustelidae restriction factor repertoires are warranted, with a view to the potential for an HIV-1 animal model.
Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis
Authors: Dobrikova Elena Y. , Goetz Christian , Walters Robert W. , Lawson Sarah K. , Peggins James O. , Muszynski Karen , Ruppel Sheryl , Poole Karyol , Giardina Steven L. , Vela Eric M. , Estep James E. , Gromeier Matthias 
Published: December 2011

ABSTRACTA dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation inMacaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.
The Human Cytomegalovirus (HCMV) Tegument Protein UL94 Is Essential for Secondary Envelopment of HCMV Virions
Authors: Phillips Stacia L. , Bresnahan Wade A. 
Published: December 2011

ABSTRACT
Human cytomegalovirus (HCMV) virions are structurally complex, and the mechanisms by which they are assembled are poorly understood. However, several tegument proteins are known to be essential for proper particle assembly and maturation. Despite intense investigation, the function of many tegument proteins remains unknown. The HCMV UL94 gene is conserved among all herpesviruses and encodes a virion protein of unknown function. We demonstrate here that UL94 is a tegument protein that is expressed with true-late kinetics and localizes to the viral assembly complex during infection. To elucidate the function of UL94, we constructed a UL94-null mutant, designated UL94stop. This mutant is completely defective for replication, demonstrating that UL94 is essential. Phenotypic analysis of the UL94stop mutant shows that in the absence of UL94, viral gene expression and genome synthesis occur at wild-type levels. However, analysis of the localization of viral proteins to the cytoplasmic assembly complex shows that the essential tegument protein UL99 (pp28) exhibits aberrant localization in cells infected with the UL94stop mutant. Finally, we show that there is a complete block in secondary envelopment in the absence of UL94. Taken together, our data suggest that UL94 functions late in infection to direct UL99 to the assembly complex, thereby facilitating secondary envelopment of virions.
Immune Correlates of Herpes Zoster in HIV-Infected Children and Youth
Authors: Weinberg Adriana , Huang Sharon , Song Lin-Ye , Fenton Terry , Williams Paige , Patterson Julie , Tovar-Salazar Adriana , Levin Myron J. 
Published: December 2011

ABSTRACT

To identify immunologic factors that modulate the risk of herpes zoster (HZ), we compared varicella-zoster virus (VZV)-specific and nonspecific T-cell subpopulations of 47 HIV-infected children before they developed HZ with those of 141 VZV-positive HZ-negative matched controls. Compared with controls, HZ cases had lower VZV-specific CD8
+
CD107a
+
cell percentages independently of CD4
+
percentages or HIV loads, suggesting that VZV-specific cytotoxic T cells are protective against HZ. In contrast, high nonspecific regulatory and activated T cells were associated with an increased risk of HZ.