bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-Linked Glycosylation Facilitates Sialic Acid-Independent Attachment and Entry of Influenza A Viruses into Cells Expressing DC-SIGN or L-SIGN
Authors: Londrigan Sarah L. , Turville Stuart G. , Tate Michelle D. , Deng Yi-Mo , Brooks Andrew G. , Reading Patrick C. 
Published: December 2010

ABSTRACTIt is widely recognized that sialic acid (SA) can mediate attachment of influenza virus to the cell surface, and yet the specific receptors that mediate virus entry are not known. For many viruses, a definitive demonstration of receptor function has been achieved when nonpermissive cells are rendered susceptible to infection following transfection of the gene encoding a putative receptor. For influenza virus, such approaches have been confounded by the abundance of SA on mammalian cells so that it has been difficult to identify cell lines that are not susceptible to infection. We examined influenza virus infection of Lec2 Chinese hamster ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells were resistant to influenza virus infection, and stable cell lines expressing either DC-SIGN or L-SIGN were generated to assess the potential of each molecule to function as SA-independent receptors for influenza A viruses. Virus strain BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca2+-dependent manner, and transfected cells were susceptible to virus infection. Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial neuraminidase, blocked infection, a finding consistent with SA-independent virus attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing either DC-SIGN or L-SIGN, whereas other glycosylated H1N1 subtype viruses could infect cells efficiently. Together, these data indicate that human C-type lectins (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses independently of cell surface SA.
A Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Interacts with Notch1 and Notch3
Authors: Workman Aspen , Sinani Devis , Pittayakhajonwut Daraporn , Jones Clinton 
Published: December 2010

ABSTRACT

Like other
A
lphaherpesvirinae
subfamily members, bovine herpesvirus 1 (BHV-1) establishes latency in sensory neurons. The latency-related RNA (LR-RNA) is abundantly expressed in latently infected sensory neurons. An LR mutant virus with stop codons at the amino terminus of the first open reading frame (ORF) in the LR gene (ORF2) does not reactivate from latency, in part because it induces higher levels of apoptosis in infected neurons. ORF2 is not the only viral product expressed during latency, but it is important for the latency reactivation cycle because it inhibits apoptosis. In this study, a yeast 2-hybrid screen revealed that ORF2 interacted with two cellular transcription factors, Notch1 and Notch3. These interactions were confirmed in mouse neuroblastoma cells by confocal microscopy and in an
in vitro
“pulldown” assay. During reactivation from latency, Notch3 RNA levels in trigeminal ganglia were higher than those during latency, suggesting that Notch family members promote reactivation from latency or that reactivation promotes Notch expression. A plasmid expressing the Notch1 intercellular domain (ICD) stimulated productive infection and promoters that encode the viral transcription factor bICP0. The Notch3 ICD did not stimulate productive infection as efficiently as the Notch1 ICD and had no effect on bICP0 promoter activity. Plasmids expressing the Notch1 ICD or the Notch3 ICD
trans
-activated a late promoter encoding glycoprotein C. ORF2 reduced the
trans
-activation potential of Notch1 and Notch3, suggesting that ORF2 interfered with the
trans
-activation potential of Notch. These studies provide evidence that ORF2, in addition to inhibiting apoptosis, has the potential to promote establishment and maintenance of latency by sequestering cellular transcription factors.
Retrovirus-Induced Spongiform Neurodegeneration Is Mediated by Unique Central Nervous System Viral Targeting and Expression of Env Alone
Authors: Li Ying , Cardona Sandra M. , Traister Russell S. , Lynch William P. 
Published: December 2010

ABSTRACT

Certain murine leukemia viruses (MLVs) can induce progressive noninflammatory spongiform neurodegeneration similar to that caused by prions. The primary MLV determinants responsible have been mapped to within the
env
gene; however, it has remained unclear how
env
mediates disease, whether non-Env viral components are required, and what central nervous system (CNS) cells constitute the critical CNS targets. To address these questions, we examined the effect of transplanting engraftable C17.2 neural stem cells engineered to pseudotype, disseminate, and
trans
-complement neurovirulent (CasBrE, CasE, and CasES) or non-neurovirulent (Friend and SFF-FE)
env
sequences (SU or SU/TM) within the CNS using either the “non-neurovirulent” amphotropic helper virus, 4070A, or p
gag-pol
gpt (a nonpackaged vector encoding Gag-Pol). These studies revealed that acute MLV-induced spongiosis results from two separable activities of Env. First, Env causes neuropathology through unique viral targeting within the CNS, which was efficiently mediated by ecotropic Envs (CasBrE and Friend), but not 4070A amphotropic Env. Second, Env induces spongiosis through a toxin activity that is MLV-receptor independent and does not require the coexpression of other viral structural proteins. CasBrE and 4070A Envs possess the toxin activity, whereas Friend Env does not. Although the identity of the critical viral target cell(s) remains unresolved, our results appear to exclude microglia and oligodendrocyte lineage cells, while implicating viral entry into susceptible neurons. Thus, MLV-induced disease parallels prionopathies in that a single protein, Env, mediates both the CNS targeting and the toxicity of the infectious agent that manifests itself as progressive vacuolar neurodegeneration.
Reversal of Heterochromatic Silencing of Quiescent Herpes Simplex Virus Type 1 by ICP0
Authors: Ferenczy Michael W. , DeLuca Neal A. 
Published: December 2010

ABSTRACT

Persisting latent herpes simplex virus genomes are to some degree found in a heterochromatic state, and this contributes to reduced gene expression resulting in quiescence. We used a relatively long-term quiescent infection model in human fibroblasts, followed by provision of ICP0 in
trans
, to determine the effects of ICP0 on the viral chromatin state as gene expression is reactivated. Expression of ICP0, even at low levels, results in a reduction of higher-order chromatin structure and heterochromatin on quiescent viral genomes, and this effect precedes an increase in transcription. Concurrent with transcriptional activation, high levels of ICP0 expression result in the reduction of the heterochromatin mark trimethylated H3K9, removal of histones H3 and H4 from the quiescent genome, and hyperacetylation of the remaining histones. In contrast, low levels of ICP0 did not appreciably change the levels of histones on the viral genome. These results indicate that ICP0 activity ultimately affects chromatin structure of quiescent genomes at multiple levels, including higher-order chromatin structure, histone modifications, and histone association. Additionally, the level of ICP0 expression affected its ability to change chromatin structure but not to reactivate gene expression. While these observations suggest that some of the effects on chromatin structure are possibly not direct, they also suggest that ICP0 exerts its effects through multiple mechanisms.
Origin and Evolution of HIV-1 in Breast Milk Determined by Single-Genome Amplification and Sequencing
Authors: Salazar-Gonzalez Jesus F. , Salazar Maria G. , Learn Gerald H. , Fouda Genevieve G. , Kang Helen H. , Mahlokozera Tatenda , Wilks Andrew B. , Lovingood Rachel V. , Stacey Andrea , Kalilani Linda , Meshnick Steve R. , Borrow Persephone , Montefiori David C. , Denny Thomas N. , Letvin Norman L. , Shaw George M. , Hahn Beatrice H. , Permar Sallie R. 
Published: December 2010

ABSTRACT

HIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. In this study, HIV envelope (
env
) genes were sequenced from virus variants amplified by single-genome amplification from plasmas and milk of 12 chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and statistical tests of compartmentalization revealed interspersion of plasma and milk HIV
env
sequences in the majority of subjects, indicating limited or no compartmentalization of milk virus variants. However, phylogenetic tree analysis further revealed monotypic virus variants that were significantly more frequent in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (
P
= 0.002), suggesting local virus replication in the breast milk compartment. Moreover, clonally amplified virus
env
genes in milk produced functional virus Envs that were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes and neutralization sensitivities to broadly neutralizing antibodies in both transmitting and nontransmitting mothers. Finally, phylogenetic comparison of longitudinal milk and plasma virus
env
sequences revealed synchronous virus evolution and new clonal amplification of evolved virus
env
genes in milk. The limited compartmentalization and the clonal amplification of evolving, functional viruses in milk indicate continual seeding of the mammary gland by blood virus variants, followed by transient local replication of these variants in the breast milk compartment.
Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not reversible in rat heart ventricles
Authors: Nouette-Gaulain Karine , Biais Matthieu , Savineau Jean-Pierre , Marthan Roger , Mazat Jean-Pierre , Letellier Thierry , Sztark François 
Published: December 2010

Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target.
SENTinel Node Biopsy before or after NeoAdjuvant Systemic Treatment – The German SENTINA Trial.
Authors: Kuehn T. , Bauerfeind I. , Fehm T. , Fleige B. , Helms G. , Liedtke C. , Mai M. , von Minckwitz G. , Staebler A. , Untch M. 
Published: December 2010

Abstract
Background: For patients with breast cancer undergoing neoadjuvant systemic treatment (NST) the optimal timing of sentinel node biopsy (SLNB) is unclear. While adequate axillary staging prior to NST could allow for a-priori tailoring of systemic treatment, SLNB after NST could spare those patients from complete axillary dissection (AD), who are free of metastases in the axilla or convert from a positive (Npos) to a negative (Nneg) axillary status following NST. For these patients, however, the reliability of SLNB to predict the axillary status remains yet to be prospectively confirmed.Material and Methods: The German SENTINA protocol, as a substudy of the German Geparquinto neoadjuvant trial of the AGO and the German Breast Group (GBG), is a 4-arm prospective multicenter case control study designed to examine the role of SLN in patients undergoing NST.Study design:Arm A before NST: clinically Nneg + negative SLN --&gt; no add. Axillary surgery Arm B before NST: clinically Nneg + positive SLN --&gt; sentinel-node-guided AD after NST Arm C before NST: clinically Npos, after NST: clinically Nneg --&gt; sentinel-node-guided AD after NST Arm D before NST: clinically Npos, after NST: clinically Npos --&gt; ADStudy objectives:1. to compare the detection rate of SLNB before and after NST2. to evaluate the number of patients with involved nodes despite being clinically Nneg before NST3. to determine the number of patients who convert from clinically Npos to histologically Nneg after NST4. to evaluate the false-negative rate of SNB for patients who convert from clinically Npos to histologically SNneg after NST5. to determine lymphatic pathway configuration, detection rate and false-negative rate of SLNB after prior SLNB6. to determine the false negative rate of intraoperative frozen section before and after NSTResults: Until now 366 patients from 30 institutions have been enrolled in this trial. 230 patients have completed primary systemic and surgical treatment. A total of 1508 patients were calculated as adequate to have the one-sided confidence interval of 95 % for the false negative rate of SLNB in the arms B and C not exceeding 10% (196 pts each). 82 pts entered arm A. Fifty-eight, 76 and 24 pts were recruited for the arms B, C and D respectively.Conclusion: To our knowledge the SENTINA trial is the first prospective multicenter study to evaluate the role of SLNB in the neoadjuvant setting. The SENTINA protocol will allow for a direct comparison of the feasibility and reproducibility of a standardized SLNB-procedure before and after NST. The study will provide reliable data on the predictive value of SLNB before and after NST in patients converting from a clinically positive to a negative axillary status and offer insights into the biology of axillary response to NST.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1008.
Evaluation of the Predictive Performance and Regimen Specificity of a 30-Gene Predictor of Pathologic Complete Response in a Prospective Randomized Neoadjuvant Clinical Trial for Stage I-III Breast Cancer.
Authors: Tabchy A. , Symmans W. , Valero V. , Vidaurre T. , Lluch A. , Qi Y. , Souchon E. , Barajas-Figueroa L. , Gomez H. , Martin M. , Coutant C. , Hess K. , Hortobagyi G. , Pusztai L. 
Published: December 2010

Abstract
Purpose: To prospectively evaluate in a randomized trial if a previously reported multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy can accurately predict pCR to neoadjuvant T/FAC chemotherapy, and if it also predicts pCR to FAC only chemotherapy. Furthermore, it is unknown if the T/FAC regimen is superior to 6 courses of FAC; therefore we compare the pCR rates for patients who receive T/FAC versus FACx6 preoperative chemotherapy.Materials and Methods: Patients with stage I-III breast cancer (n=273) were randomly assigned to receive either 12 courses of weekly paclitaxel followed by 4 courses of FAC (T/FAC, n=138), or 6 courses of FAC (FACx6, n=135) neoadjuvant chemotherapy. All patients underwent a pretreatment FNA biopsy of the tumor for gene expression profiling on oligonucleotide microarrays, and treatment response prediction (pCR versus residual disease, RD) was performed using the multigene predictor. Predicted and observed pathologic responses were compared independently in the two treatment arms.Results: The pCR rate was 19% with T/FAC and 9% with FACx6 (p&lt;0.05). In the T/FAC arm, the positive predictive value (PPV) of the genomic predictor was 38% (95%CI:21-56%), the negative predictive value (NPV) 88% (CI:77-95%), sensitivity 63% (CI:38-84%), specificity 72% (CI:60-82%), and the AUC 0.711. In the FAC only treatment arm, the PPV was 9% (CI:1-29%), the NPV 92% (CI:83-97%), sensitivity 29% (CI:4-71%), specificity 75% (CI:64-84%), and the AUC 0.584. This suggests that the genomic predictor is regimen-specific. In a multivariate analysis including age, tumor size, nodal status, histologic grade, HER2 and estrogen receptor (ER) status and the genomic predictor, only ER status was a significant predictor of pCR.Discussion: Pathologic complete response rate was significantly higher in the T/FAC arm compared to the FACx6 arm indicating a higher efficacy of the paclitaxel containing arm. Patients who were predicted to achieve pCR to T/FAC had a significantly higher pCR rate (38%) than unselected patients (19%) or patients predicted to have RD (12%) when treated with this regimen. These results confirm that the multigene predictor can identify patients with greater than average sensitivity to T/FAC chemotherapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 101.
Pre-Operative Axillary Nodal Staging by Ultrasonography and Fine-Needle Cytology Reduces the Number of Unnecessary Sentinel Node Biopsies in Breast Cancer Patients.
Authors: Baruah B. , Goyal A. , Young P. , Douglas-Jones A. , Mansel R. , on Behalf of Cardiff Breast Unit . 
Published: December 2010

Abstract
Aims: The role of pre-operative axillary ultrasound for nodal staging in early breast cancer patients is evolving. In this study, we evaluated the role of axillary ultrasound (AUS) and fine-needle aspiration cytology (FNAC) to stage the axilla pre-operatively in a large series of operable breast cancer patients including its role in the detection of nodal micrometastases. A second objective was to ascertain whether a significant learning curve is associated with this technique.Methods: Between October 2006 and March 2009, all patients diagnosed with invasive breast cancer in our unit had an AUS pre-operatively. Patients with suspicious nodes on ultrasound underwent FNAC. Cytology positive patients proceeded directly to axillary clearance, while others underwent sentinel lymph node biopsy. Data from this retrospective study was analyzed using appropriate statistical techniques to evaluate the efficacy of this technique to detect nodal metastases pre-operatively.Results: 495 patients scheduled to undergo surgery for invasive breast cancer were included in this study. 7 patients had bilateral malignancies and, therefore, a total of 502 axillae were examined using ultrasound. The median age of patients in our study was 61 years (range 32-91). 137 patients (27.3%) had proven nodal metastases on final histology. 39 of 137 (28.5%) node positive patients were accurately identified by pre-operative AUS and FNAC and, therefore, spared an unnecessary sentinel node biopsy. The combined technique of AUS and FNAC had an overall accuracy of 80.5% (95% CI: 76.8-83.7), sensitivity of 28.5% (95% CI: 21.6-36.5), specificity of 100% (95% CI: 99-100), positive predictive value of 100% (95% CI: 91-100), and negative predictive value of 78.8% (95% CI: 74.9-82.3). Pre-operative AUS and FNAC was normal in all patients with nodal micrometastases (n=15) and isolated tumour cells (n=11) on histopathology. No significant learning curve was demonstrated for this technique in our study. Overall, 28.5% of node positive patients and 7.9% of all breast cancer patients avoided an unnecessary sentinel node biopsy due to this procedure.Conclusions: Pre-operative AUS and FNAC is an inexpensive, minimally-invasive outpatient procedure with an accuracy of more than 80% that can avoid unnecessary sentinel lymph node biopsy in 28.7% of node positive patients. It has no role in the detection of nodal micrometastases and there is no demonstrable learning curve seen with this technique.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1018.
Can We Skip Sentinel Lymph Node Biopsy in Patients Who Have Microinvasive Breast Cancer?
Authors: Ko B. , Seo J. , Kwon S. , Lee Y. , Lim W. , Lee J. , Kim H. , Jang M. , Ku B. , Son B. , Ahn S. 
Published: December 2010

Abstract
Background: Sentinel lymph node(SLN) biopsy in patients with ductal carcinoma in situ(DCIS) was controversial. We may skip SLN biopsy when we performed conserving operation with small sized DCIS. But sometimes we can find DCIS with micro-invasive breast cancer (MIC) after operation. Should another operation be performed? We determined the incidence of positive axillary lymph node (ALNs) in patients with MIC, and the predictive factors of ALNs metastasis in these patients. Methods: Between July 1989 and January 2008, 9046 patients had operations performed on invasive breast cancers at Asan Medical Center. From July1989 to February 2003, ALND was performed to surgically stage the axilla. Since May 2003, SNB has been routinely performed for all cases. Patients who were treated with neoadjuvant chemotherapy and those who had no identifiable ALNs at surgery were excluded from the study. We retrospectively checked clinical and pathologic variables including diagnosis, patient demographics, size of DCIS, grade, multi-focal lesion, hormone receptor status, lymphatic invasion status etc. Results: 265 patients were identified with microinvasive (pathologic stage T1mic) breast cancer. Among these patients, 12 patients didn't have ALN study. 2 patients had bilateral MIC. The research was conducted on the remaining 255 cases. There were 13 cases of ALN metastases identified in this group of patients(5%). Young age (p=0.006), multifocal lesion (p=0.040) and lymphatic invasion (p&lt;0.0001) were predictive factors for ALN metastases. There was no incidence of metastatic ALNs among the old age (≥50) patients of this group. Conclusion: As the incidence of ALN metastases in MIC patients is very small, particularly in those who had no lymphatic invasion, single lesion and among old age patients. So we think conservative treatment is one of the available options for these patients. However, due to the size of the subject group in this study, it needs to be validated through extensive prospective research.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1019.