bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1
Authors: Datta Sibnarayan , Hazari Sidhartha , Chandra Partha K , Samara¹ Maria , Poat Bret , Gunduz Feyza , Wimley William C , Hauser Hansjorg , Koster Mario , Lamaze Christophe , Balart Luis A , Garry Robert F , Dash Srikanta 
Published: July 2011

AbstractThe mechanisms underlying the Hepatitis C virus (HCV) resistance to interferon alpha (IFN-α) are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1), IFN-α receptor 2 (IFNAR2), Jak1, Tyk2, Stat1, Stat2 and the ISRE- luciferase reporter plasmid. We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-α resistant cell lines (R-15, R-17 and R-24) used in this study. Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-α resistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1) of IFNAR1. In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4) of IFNAR1 protein leading to impaired activation of Tyk2 kinase. Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-α. HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER) stress mechanisms. The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-α.
Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
Authors: Makarova Kira S , Aravind L , Wolf Yuri I , Koonin Eugene V 
Published: July 2011

Abstract

Background
The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III).

Results
A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes.

Conclusions
Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution.

Open peer review
This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia), Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.
Embryonic stem cells in scaffold-free three-dimensional cell culture: osteogenic differentiation and bone generation
Authors: Handschel Jörg , Naujoks Christian , Depprich Rita , Lammers Lydia , Kübler Norbert , Meyer Ulrich , Wiesmann Hans-Peter 
Published: July 2011

Abstract
Extracorporeal formation of mineralized bone-like tissue is still an unsolved challenge in tissue engineering. Embryonic stem cells may open up new therapeutic options for the future and should be an interesting model for the analysis of fetal organogenesis. Here we describe a technique for culturing embryonic stem cells (ESCs) in the absence of artificial scaffolds which generated mineralized miromasses. Embryonic stem cells were harvested and osteogenic differentiation was stimulated by the addition of dexamethasone, ascorbic acid, and ß-glycerolphosphate (DAG). After three days of cultivation microspheres were formed. These spherical three-dimensional cell units showed a peripheral zone consisting of densely packed cell layers surrounded by minerals that were embedded in the extracellular matrix. Alizarine red staining confirmed evidence of mineralization after 10 days of DAG stimulation in the stimulated but not in the control group. Transmission electron microscopy demonstrated scorching crystallites and collagenous fibrils as early indication of bone formation. These extracellular structures resembled hydroxyl apatite-like crystals as demonstrated by distinct diffraction patterns using electron diffraction analysis. The micromass culture technique is an appropriate model to form three-dimensional bone-like micro-units without the need for an underlying scaffold. Further studies will have to show whether the technique is applicable also to pluripotent stem cells of different origin.
Organic parasite control for poultry and rabbits in British Columbia, Canada
Authors: Lans Cheryl , Turner Nancy 
Published: July 2011

AbstractPlants used for treating endo- and ectoparasites of rabbits and poultry in British Columbia included Arctium lappa (burdock), Artemisia sp. (wormwood), Chenopodium album (lambsquarters) and C. ambrosioides (epazote), Cirsium arvense (Canada thistle), Juniperus spp. (juniper), Mentha piperita (peppermint), Nicotiana sp. (tobacco), Papaver somniferum (opium poppy), Rubus spp. (blackberry and raspberry relatives), Symphytum officinale (comfrey), Taraxacum officinale (common dandelion), Thuja plicata (western redcedar) and Urtica dioica (stinging nettle).
High energy tibial plateau fractures treated with hybrid external fixation
Authors: Babis George C , Evangelopoulos Dimitrios S , Kontovazenitis Panagiotis , Nikolopoulos Konstantinos , Soucacos Panagiotis N 
Published: July 2011

AbstractManagement of high energy intra-articular fractures of the proximal tibia, associated with marked soft-tissue trauma, can be challenging, requiring the combination of accurate reduction and minimal invasive techniques. The purpose of this study was to evaluate whether minimal intervention and hybrid external fixation of such fractures using the Orthofix system provide an acceptable treatment outcome with less complications. Between 2002 and 2006, 33 patients with a median ISS of 14.3 were admitted to our hospital, a level I trauma centre, with a bicondylar tibial plateau fracture. Five of them sustained an open fracture. All patients were treated with a hybrid external fixator. In 19 of them, minimal open reduction and stabilization, by means of cannulated screws, was performed. Mean follow-up was 27 months (range 24 to 36 months). Radiographic evidence of union was observed at 3.4 months (range 3 to 7 months). Time for union was different in patients with closed and grade I open fractures compared to patients with grade II and III open fractures. One non-union (septic) was observed (3.0%), requiring revision surgery. Pin track infection was observed in 3 patients (9.1%).Compared to previously reported series of conventional open reduction and internal fixation, hybrid external fixation with or without open reduction and minimal internal fixation with the Orthofix system, was associated with satisfactory clinical and radiographic results and limited complications.
At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study
Authors: Sbidian Emilie , Bastuji-Garin Sylvie , Valeyrie-Allanore Laurence , Ferkal Salah , Lefaucheur Jean P , Drouet Alain , Brugière Pierre , Vialette Cédric , Combemale Patrick , Barbarot Sébastien , Wolkenstein Pierre ,   NF France Network
Published: July 2011

Abstract

Objectives
To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas.

Patients and methods
Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category).

Results
Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas.

Conclusion
The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.

Registration details
ORPHA86301
Upper cervical intramedullary spinal metastasis of ovarian carcinoma: a case report and review of the literature
Authors: Miranpuri Amrendra S , Rajpal Sharad , Salamat M Shahriar , Kuo John S 
Published: July 2011

Abstract

Introduction
Currently there is no generalized approach to treating patients with intra-medullary spinal metastasis. High cervical spinal cord lesions can be particularly challenging cases, and may even be considered inoperable by some.

Case report
We present what is, to the best of our knowledge, the first reported case of ovarian carcinoma (managed primarily with surgery) in a 65-year-old Caucasian woman metastasizing to the upper cervical spinal cord; we also review the relevant literature and discuss management strategies.

Conclusions
Due to improving systemic cancer therapies, patients with cancer now often survive longer and are more likely to develop central nervous system metastases. Therefore, neurosurgical oncologists are often challenged with difficult decisions about how to surgically manage these patients. We recommend individualized multidisciplinary management based on patient functional status, the need for definitive diagnosis for possible additional adjuvant therapies, and consideration of extent of systemic disease impacting on desirable quality and length of survival.
FOXO3 Is Inhibited by Oncogenic PI3K/Akt Signaling but Can Be Reactivated by the NSAID Sulindac Sulfide
Authors: Weidinger Carl , Krause Kerstin , Mueller Kathrin , Klagge Antje , Fuhrer Dagmar , Führer-Sakel Dagmar 
Published: July 2011

Abstract

Background:
Overactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a pivotal trigger of thyroid carcinogenesis. Recent findings from other tumor entities revealed that PI3K/Akt-driven carcinogenesis critically involves the inactivation of the tumor-suppressive transcription factor Forkhead box O (FOXO)-3. However, little is known about FOXO3 in the thyroid context.

Aims:
We sought to investigate the influence of the thyroid oncogenes BRAFV600E, H-RASV12, and p110α (H1074R) on the regulation of the PI3K downstream target FOXO3 in vitro. Furthermore, the impact of the expression of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) on the transcriptional activity of FOXO3 was assessed in a panel of 44 human thyroid tumors. Finally, we tried to modulate FOXO3 activity pharmacologically with help of the nonsteroidal antiinflammatory drug sulindac sulfide (SS).

Results:
We found that the overexpression of p110α H1074R results in the inactivation of FOXO3 via its nuclear exclusion. In vivo, we observed a direct correlation between PTEN expression and the transcriptional activation of FOXO3. In vitro, we found that stimulation with SS reversed PI3K/Akt-driven inactivation of FOXO3, resulting in its nuclear relocation and a combined induction of the antiproliferative FOXO target genes Gadd45α and p27kip1 and the proapoptotic FOXO target gene Bim in benign (FRTL-5) and malignant human thyrocytes (FTC-133). In agreement with this, SS promoted the cell cycle arrest and apoptosis in thyroid cells, which could be amplified by the transfection of exogenous FOXO3.

Conclusion:
Our data suggest that deregulation of proapoptotic FOXO3 represents a central step in PI3K/Akt-mediated thyroid carcinogenesis. Thus, SS might represent an attractive pharmacological tool for targeting thyroid neoplasia with aberrant PI3K/Akt/FOXO3 signaling.
Standardized Multidisciplinary Evaluation Yields Significant Previously Undiagnosed Morbidity in Adult Women with Turner Syndrome
Authors: Freriks Kim , Timmermans Janneke , Beerendonk Catharina C. M. , Verhaak Chris M. , Netea-Maier Romana T. , Otten Barto J. , Braat Didi D. M. , Smeets Dominique F. C. M. , Kunst Dirk H. P. M. , Hermus Ad R. M. M. , Timmers Henri J. L. M. 
Published: July 2011

Abstract

Context:
Besides short stature and gonadal dysgenesis, Turner syndrome (TS) is associated with various abnormalities. Adults with TS have a reduced life expectancy, mainly related to structural abnormalities of the heart and aorta, and an increased risk of atherosclerosis.

Objective:
Our objective was to investigate the yield of an initial standardized multidisciplinary screening in adult TS patients.

Design and Setting:
This was an observational study at a multidisciplinary care unit for adult women with TS.

Participants:
Participants were adult women with TS (n = 150). Mean age was 31.0 ± 10.4 yr, with 47% karyotype 45,X.

Interventions:
All women were consulted by an endocrinologist, a gynecologist, a cardiologist, an otorhinolaryngologist, and when indicated, a psychologist. The screening included magnetic resonance imaging of the heart and aorta, echocardiography, electrocardiogram, dual-energy x-ray absorptiometry, renal ultrasound, audiogram, and laboratory investigations according to international expert recommendations.

Main outcome measures:
New diagnoses and prevalence of TS-associated morbidity were evaluated.

Results:
Thirty percent of patients currently lacked medical follow-up, and 15% lacked estrogen replacement therapy in the recent last years. The following disorders were newly diagnosed: bicuspid aortic valve (n = 13), coarctation of the aorta (n = 9), elongation of the transverse aortic arch (n = 27), dilation of the aorta (n = 34), osteoporosis (n = 8), osteopenia (n = 56), renal abnormalities (n = 7), subclinical hypothyroidism (n = 33), celiac disease (n = 3), glucose intolerance (n = 12), dyslipidemia (n = 52), hypertension (n = 39), and hearing loss warranting a hearing aid (n = 8). Psychological consultation was needed in 23 cases.

Conclusions:
Standardized multidisciplinary evaluation of adult women with TS as advocated by expert opinion is effective and identifies significant morbidity. Girls with TS benefit from a careful transition to ongoing adult medical care.
Is There a Role for Fatty Acid Synthase in the Diagnosis of Prostatic Adenocarcinoma?
Authors: Wu Xiaojun , Zayzafoon Majd , Zhang Xinzhi , Hameed Omar 
Published: July 2011

Abstract
Our aim was to compare the usefulness of fatty acid synthase (FASn) with that of α-methylacyl coenzyme-A racemase (AMACR) in the diagnosis of prostatic adenocarcinoma. The expression of these 2 markers was compared in a tissue microarray containing 62 foci of benign glands and 36 foci of prostatic adenocarcinoma. Similar to AMACR, there was significantly higher FASn expression in adenocarcinoma compared with that in benign glands. The optimal accuracy rate and area under curve (AUC) by receiver operating characteristic analysis for FASn were not significantly different from those for AMACR (accuracy, 80% vs 87%; AUC, 0.942 vs 0.956; P for both, &gt; .05). Moreover, in cases with coexistent malignant and benign glands on the same core, FASn could selectively distinguish a proportion of cases (17/21 [81%]) similar to using AMACR. We conclude that FASn may aid in the diagnosis of prostatic adenocarcinoma, at least to supplement AMACR as another positive marker of carcinoma and potentially increase diagnostic accuracy.
Marginal Zone Lymphomas With Plasmacytic Differentiation and Related Disorders
Authors: Molina Thierry J. , Lin Pei , Swerdlow Steven H. , Cook James R. 
Published: July 2011

Abstract
Marginal zone lymphomas of all types (nodal, splenic, and extranodal mucosa-associated lymphoid tissue [MALT]) may show plasmacytic differentiation. Distinguishing marginal zone lymphomas from other small B-cell lymphomas with plasmacytic differentiation, especially lymphoplasmacytic lymphoma, or from plasma cell neoplasms may be challenging. Marginal zone lymphomas with plasmacytic differentiation were discussed in 2 sessions of the 2009 Society for Hematopathology/European Association for Haematopathology Workshop. Session 4 focused on nodal marginal zone lymphomas, including cases exhibiting classic features and cases displaying atypical phenotypes. The difficulties of classification of cases with increased numbers of large cells were also discussed. Session 5 examined nonnodal marginal zone lymphomas and related entities, including splenic marginal zone lymphoma, MALT lymphoma, γ heavy chain disease, and cryoglobulin-associated lymphoproliferative disorders. These cases illustrate the importance of clinical data and, in some cases, phenotypic and cytogenetic findings in appropriately applying the 2008 World Health Organization criteria.
Importance of Papanicolaou Staining for Sperm Morphologic Analysis
Authors: Singh Smita , Sharma Sunita , Jain Manjula , Chauhan Richa 
Published: July 2011

Abstract
Without experience or proper training, the evaluation of the morphologic features of sperm can become the most confusing and time-consuming area of semen analysis. This study defined the role of Papanicolaou staining compared with an automated sperm analyzer in the management of infertility. We compared the morphologic features of sperm using Papanicolaou staining and an automated Sperm Quality Analyzer IIC-P (SQA-IIC-P; Medical Electronic Systems, Caesarea, Israel) and evaluated the role of factors affecting these features in semen samples from 201 infertile men. The sensitivity of the SQA-IIC-P was 85.5%, and the specificity was 87.3% compared with Papanicolaou staining. Although the positive predictive value of this instrument was 93.7%, the negative predictive value was only 73.3%. Moreover, sperm indices that are important for in vitro fertilization could be derived only by using the manual method. A strong correlation was seen with smoking and leukocytospermia (P &lt; .001).
The SQA-IIC-P can be used as a screening tool to evaluate the morphologic features of sperm. However, Papanicolaou staining to study the cytomorphologic features of sperm and the calculation of sperm indices should be done for quantification of defects.
Improved Flagging Rates on the Sysmex XE-5000 Compared With the XE-2100 Reduce the Number of Manual Film Reviews and Increase Laboratory Productivity
Authors: Briggs Carol J. , Linssen Joachim , Longair Ian , Machin Samuel J. 
Published: July 2011

AbstractHematology analyzers generate suspect flags in the presence of abnormal cells. False-positive rates for flags are high on all analyzers. Sysmex, Kobe, Japan, has developed new software for its XE-5000 with improved algorithms for flagging blast cells, abnormal lymphocytes or lymphoblasts, and atypical lymphocytes.This study evaluated the efficiency of these flags in 1,002 samples. The XE-5000 was compared with the XE-2100 (Sysmex) and microscopic examination of cell morphologic features.On the XE-2100, the blast flag demonstrated 90 false-positives, 13 true-positives, and 3 false-negatives. The values on the XE-5000 were 27 false-positives, 14 true-positives, and 2 false-negatives. The abnormal lymphocyte/lymphoblast flag was assessed with the atypical lymphocyte flag. The XE-2100 showed 114 false-positives, 23 true-positives, and 20 false-negatives, and on the XE-5000, there were 45 false-positives, 22 true-positives, and 21 false-negatives.This more specific flagging reduces the number of films that require manual review.
Use of the BD Vacutainer Rapid Serum Tube Reduces False-Positive Results for Selected Beckman Coulter Unicel DxI Immunoassays
Authors: Strathmann Frederick G. , Ka Michael M. , Rainey Petrie M. , Baird Geoffrey S. 
Published: July 2011

Abstract
We investigated the use of serum samples from BD Vacutainer rapid serum tubes (RSTs; BD, Franklin Lakes, NJ) to reduce undetermined interferences contributing to false-positive immunoassay results in heparin plasma samples. Patients being evaluated for suspected myocardial infarction had specimens drawn into an RST in addition to the standard lithium-heparin plasma separator tube (PST). We measured 28 separate analytes in both specimens using immunoassay, electrochemical, and spectrophotometric methods. Higher results were observed in some PST specimens tested for troponin I, creatine kinase-MB isoenzyme, human chorionic gonadotropin, and thyroid-stimulating hormone. These discrepancies were investigated by repeating analyses after recentrifugation of both specimens. Reanalysis gave results for the PST specimens that were lower and agreed well with initial results from RSTs, suggesting false-positive rates of 10.8% for troponin I and about 2% for each of the other 3 analytes. Overall, specimens collected in RSTs had fewer false-positive immunoassay results than specimens collected in plasma separator tubes.