bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulation of a Novel Pattern of Infections by Enteric Adenovirus Serotype 41 among Children below 5 Years of Age in Kolkata, India
Authors: Dey Rakhi Sharma , Ghosh Santanu , Chawla-Sarkar Mamta , Panchalingam Sandra , Nataro James P. , Sur Dipika , Manna Byomkesh , Ramamurthy Thandavarayan 
Published: December 2010

ABSTRACT
Human adenovirus of strains subgenus F (AdV F) are the most common strains detected in acute gastroenteritis cases in developing countries. Subgenus F is represented by AdV serotype 40 (AdV-40) and AdV-41. Most of the reports have described the predominance of AdV-41 in acute gastroenteritis cases. To gain insight into the epidemiology and genetic variation of AdV-41 strains, we analyzed 1,053 stool specimens from children with diarrhea. Among them, 42 (4.0%) and 56 (5.3%) were positive for enteric adenovirus 40/41 by enzyme-linked immunosorbent assay (ELISA) and PCR, respectively. For 1,305 asymptomatic children, 9 (0.7%) and 22 (1.7%) samples were positive for enteric adenovirus 40/40 by ELISA and PCR, respectively. The age distribution revealed a higher frequency (90%) in children <24 months of age. AdV F infection was observed at a low frequency throughout the year, with an increased incidence occurring during February and March. Sequence analysis of one to three hypervariable regions (HVRs) of the hexon genes of 16 representative AdV-41 strains in this study confirmed circulation of a unique strain with genomic type cluster 1 (GTC1)/GTC2. However, sequence analysis of the fiber genes of these strains confirmed 15 amino acid deletions from the 15th repeat motif of the shaft region. The existence of two GTCs reflects the accumulation of amino acid mutations in the HVR of the hexon gene. The novel AdV-41 strain might follow the same infection pattern as AdV-40. There is no significant variation in the sequences of hexon and fiber genes among strains from symptomatic and asymptomatic children. Our data confirm the circulation of an AdV-41 strain with a novel pattern in Kolkata, India, among children below 5 years of age.
Inhibition of Influenza Virus Infection in Human Airway Cell Cultures by an Antisense Peptide-Conjugated Morpholino Oligomer Targeting the Hemagglutinin-Activating Protease TMPRSS2
Authors: Böttcher-Friebertshäuser Eva , Stein David A. , Klenk Hans-Dieter , Garten Wolfgang 
Published: December 2010

ABSTRACT

Influenza A viruses constitute a major and ongoing global public health concern. Current antiviral strategies target viral gene products; however, the emergence of drug-resistant viruses highlights the need for novel antiviral approaches. Cleavage of the influenza virus hemagglutinin (HA) by host cell proteases is crucial for viral infectivity and therefore presents a potential drug target. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded-DNA-like antisense agents that readily enter cells and can act as antisense agents by sterically blocking cRNA. Here, we evaluated the effect of PPMO targeted to regions of the pre-mRNA or mRNA of the HA-cleaving protease TMPRSS2 on proteolytic activation and spread of influenza viruses in human Calu-3 airway epithelial cells. We found that treatment of cells with a PPMO (T-ex5) designed to interfere with TMPRSS2 pre-mRNA splicing resulted in TMPRSS2 mRNA lacking exon 5 and consequently the expression of a truncated and enzymatically inactive form of TMPRSS2. Altered splicing of TMPRSS2 mRNA by the T-ex5 PPMO prevented HA cleavage in different human seasonal and pandemic influenza A viruses and suppressed viral titers by 2 to 3 log
10
units, strongly suggesting that TMPRSS2 is responsible for HA cleavage in Calu-3 airway cells. The data indicate that PPMO provide a useful reagent for investigating HA-activating proteases and may represent a promising strategy for the development of novel therapeutics to address influenza infections.
Hypervariable Region 1 Differentially Impacts Viability of Hepatitis C Virus Strains of Genotypes 1 to 6 and Impairs Virus Neutralization
Authors: Prentoe Jannick , Jensen Tanja B. , Meuleman Philip , Serre Stéphanie B. N. , Scheel Troels K. H. , Leroux-Roels Geert , Gottwein Judith M. , Bukh Jens 
Published: December 2010

ABSTRACT

Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma Huh7.5 cells. The 2a
ΔHVR1
, 5a
ΔHVR1
, and 6a
ΔHVR1
Core-NS2 recombinants retained viability in Huh7.5 cells, whereas 1a
ΔHVR1
, 1b
ΔHVR1
, 2b
ΔHVR1
, 3a
ΔHVR1
, and 4a
ΔHVR1
recombinants were severely attenuated. However, except for recombinant 4a
ΔHVR1
, viruses eventually spread, and reverse genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a
ΔHVR1
, 1b
ΔHVR1
, 2b
ΔHVR1
, and 3a
ΔHVR1
recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ∼1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles for the original viruses with these genotypes. In contrast, all HVR1-deleted viruses were highly sensitive with similar neutralization profiles.
In vivo
relevance for the role of HVR1 in protecting HCV from neutralization was demonstrated by
ex
vivo
neutralization of 2a and 2a
ΔHVR1
produced in human liver chimeric mice. Due to the high density and neutralization susceptibility of HVR1-deleted viruses, we investigated whether a correlation existed between density and neutralization susceptibility for the original viruses with genotypes 1 to 6. Only the 2a virus displayed such a correlation. Our findings indicate that HVR1 of HCV shields important conserved neutralization epitopes with implications for viral persistence, immunotherapy, and vaccine development.
A Systematic Analysis of Human Papillomavirus (HPV) E6 PDZ Substrates Identifies MAGI-1 as a Major Target of HPV Type 16 (HPV-16) and HPV-18 Whose Loss Accompanies Disruption of Tight Junctions
Authors: Kranjec Christian , Banks Lawrence 
Published: December 2010

ABSTRACTThe E6 proteins from high-risk, cancer-causing types of human papillomavirus (HPV) are characterized by the presence of a PDZ (PSD95/Dlg/ZO-1) binding motif in their extreme carboxy termini, through which they interact with a number of cellular PDZ domain-containing substrates. In order to ascertain how many of these are degraded by E6in vivo, we performed an extensive analysis of the effects of E6 ablation on the expression levels of a number of previously reported E6 PDZ substrates. Using HPV type 16 (HPV-16)-positive CaSKi cells and HPV-18-positive HeLa cells, we have found that MAGI-1 is a major degradation target of both HPV-16 and HPV-18 E6. In contrast, hDlg, hScrib, PTPN3, TIP2, FAP1, and PSD95 all exhibit various degrees of susceptibility to E6-induced degradation, and a high degree of HPV type specificity is observed for certain substrates. We also show that E6 preferentially targets MAGI-1 within the nucleus and at membrane sites. One of the direct consequences of MAGI-1 degradation is a loss of tight-junction integrity, as determined by mislocalization of the tight-junction protein ZO-1. Ablation of E6 expression restores tight junctions, and this restoration is dependent on the presence of MAGI-1. These results demonstrate that oncogenic HPV E6 proteins disrupt cellular tight junctions through the degradation of MAGI-1, and they provide further evidence of how the PDZ binding potential of E6 can contribute to HPV-induced malignancy.
Impact of Valency of a Glycoprotein B-Specific Monoclonal Antibody on Neutralization of Herpes Simplex Virus
Authors: Krawczyk Adalbert , Krauss Jürgen , Eis-Hübinger Anna M. , Däumer Martin P. , Schwarzenbacher Robert , Dittmer Ulf , Schneweis Karl E. , Jäger Dirk , Roggendorf Michael , Arndt Michaela A. E. 
Published: December 2010

ABSTRACTHerpes simplex virus (HSV) glycoprotein B (gB) is an integral part of the multicomponent fusion system required for virus entry and cell-cell fusion. Here we investigated the mechanism of viral neutralization by the monoclonal antibody (MAb) 2c, which specifically recognizes the gB of HSV type 1 (HSV-1) and HSV-2. Binding of MAb 2c to a type-common discontinuous epitope of gB resulted in highly efficient neutralization of HSV at the postbinding/prefusion stage and completely abrogated the viral cell-to-cell spreadin vitro. Mapping of the antigenic site recognized by MAb 2c to the recently solved crystal structure of the HSV-1 gB ectodomain revealed that its discontinuous epitope is only partially accessible within the observed multidomain trimer conformation of gB, likely representing its postfusion conformation. To investigate how MAb 2c may interact with gB during membrane fusion, we characterized the properties of monovalent (Fab and scFv) and bivalent [IgG and F(ab′)2] derivatives of MAb 2c. Our data show that the neutralization capacity of MAb 2c is dependent on cross-linkage of gB trimers. As a result, only bivalent derivatives of MAb 2c exhibited high neutralizing activityin vitro. Notably, bivalent MAb 2c not only was capable of preventing mucocutaneous disease in severely immunodeficient NOD/SCID mice upon vaginal HSV-1 challenge but also protected animals even with neuronal HSV infection. We also report for the first time that an anti-gB specific monoclonal antibody prevents HSV-1-induced encephalitis entirely independently from complement activation, antibody-dependent cellular cytotoxicity, and cellular immunity. This indicates the potential for further development of MAb 2c as an anti-HSV drug.
Coupled Coincidence Point and Coupled Common Fixed Point Theorems in Partially Ordered Metric Spaces with "Equation missing" -Distance
Authors: Abbas Mujahid , Ilić Dejan , Khan MuhammadAli 
Published: December 2010

AbstractWe introduce the concept of a "Equation missing"-compatible mapping to obtain a coupled coincidence point and a coupled point of coincidence for nonlinear contractive mappings in partially ordered metric spaces equipped with "Equation missing"-distances. Related coupled common fixed point theorems for such mappings are also proved. Our results generalize, extend, and unify several well-known comparable results in the literature.
Cytokine Receptor CXCR4 Mediates Estrogen-Independent Tumorigenesis, Metastasis, and Resistance to Endocrine Therapy in Human Breast Cancer
Authors: Rhodes Lyndsay V. , Short Sarah P. , Neel Nicole F. , Salvo Virgilio A. , Zhu Yun , Elliott Steven , Wei Yongkun , Yu Dihua , Sun Menghong , Muir Shannon E. , Fonseca Juan P. , Bratton Melyssa R. , Segar Chris , Tilghman Syreeta L. , Sobolik-Delmaire Tammy , Horton Linda W. , Zaja-Milatovic Snjezana , Collins-Burow Bridgette M. , Wadsworth Scott , Beckman Barbara S. , Wood Charles E. , Fuqua Suzanne A. , Nephew Kenneth P. , Dent Paul , Worthylake Rebecca A. , Curiel Tyler J. , Hung Mien-Chie , Richmond Ann , Burow Matthew E. 
Published: December 2010

Abstract
Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1–CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1–CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival irrespective of the status of the estrogen receptor (ER). Constitutive activation of CXCR4 in poorly metastatic MCF-7 cells led to enhanced tumor growth and metastases that could be reversed by CXCR4 inhibition. CXCR4 overexpression in MCF-7 cells promoted estrogen independence in vivo, whereas exogenous SDF-1 treatment negated the inhibitory effects of treatment with the anti-estrogen ICI 182,780 on CXCR4-mediated tumor growth. The effects of CXCR4 overexpression were correlated with SDF-1–mediated activation of downstream signaling via ERK1/2 and p38 MAPK (mitogen activated protein kinase) and with an enhancement of ER-mediated gene expression. Together, these results show that enhanced CXCR4 signaling is sufficient to drive ER-positive breast cancers to a metastatic and endocrine therapy-resistant phenotype via increased MAPK signaling. Our findings highlight CXCR4 signaling as a rational therapeutic target for the treatment of ER-positive, estrogen-independent breast carcinomas needing improved clinical management. Cancer Res; 71(2); 603–13. ©2010 AACR.
Integrating Conflict Detection and Attentional Control Mechanisms
Authors: Walsh Bong J. , Buonocore Michael H. , Carter Cameron S. , Mangun George R. 
Published: December 2010

AbstractHuman behavior involves monitoring and adjusting performance to meet established goals. Performance-monitoring systems that act by detecting conflict in stimulus and response processing have been hypothesized to influence cortical control systems to adjust and improve performance. Here we used fMRI to investigate the neural mechanisms of conflict monitoring and resolution during voluntary spatial attention. We tested the hypothesis that the ACC would be sensitive to conflict during attentional orienting and influence activity in the frontoparietal attentional control network that selectively modulates visual information processing. We found that activity in ACC increased monotonically with increasing attentional conflict. This increased conflict detection activity was correlated with both increased activity in the attentional control network and improved speed and accuracy from one trial to the next. These results establish a long hypothesized interaction between conflict detection systems and neural systems supporting voluntary control of visual attention.
Neurocognitive recovery in SMART syndrome: A case report
Authors: Bradshaw Jennifer , Chen Luke , Saling Michael , Fitt Greg , Hughes Andrew , Dowd Ariane 
Published: December 2010

Introduction: Stroke-like migraine attacks after radiation therapy, or SMART syndrome, is characterised by migraine-like headache with or without aura, transient neurological dysfunction, including seizures, and gyriform enhancement on magnetic resonance imaging (MRI) which resolves over a period of weeks. Detailed neuropsychological characterisation in SMART syndrome is lacking and there are no published data on the course and pattern of neurocognitive recovery. Results: The acute clinical presentation was one of unstable, fluctuating neurocognitive disturbances, complicated by seizure activity, followed by a longer term lag in the recovery of focal neuropsychological deficits which, we believe, was due to the more slowly resolving cerebral effects of SMART. Conclusions: To our knowledge, this is the first case of SMART syndrome in which neuropsychological functioning has been comprehensively and serially examined. This case is also unique due to the development of complex partial seizures. We suggest that epileptiform activity during clinical seizures should not be regarded as inconsistent with a diagnosis of SMART, provided that the seizures do not explain the onset of the other clinical and radiological features.
Prevalence of red ear syndrome in juvenile primary headaches
Authors: Raieli V , Compagno A , Brighina F , Franca G La , Puma D , Ragusa D , Savettieri G , D’Amelio M 
Published: December 2010

Background: Previous studies have suggested a relationship between ‘red ear syndrome’ (RES) and pediatric migraine. Aims of this study were (i) to assess the frequency, specificity and sensitivity of RES in a population of pediatric migraineurs and (ii) to establish the pathophysiological mechanisms of RES associated with migraine. Methods and results: A total of 226 children suffering from headache (aged 4–17 years) were enrolled. One hundred and seventy-two (76.4%) were affected by migraine, the remaining 54 (23.6%) by other primary headaches. RES was followed significantly more frequently by migraine (23.3%; p < .0001), and was characterized by high specificity and positive predictive value (96.3 and 95.3%, respectively). According to the univariate statistical analysis, RES showed a statistically significant association with male gender, throbbing quality of the pain, vomiting and phonophobia. It was confirmed by a multivariate stepwise logistic regression model only for the throbbing quality of the pain, vomiting and male gender. Conclusions: Our study showed that (i) in children, RES is a highly specific sign for migraine. In addition, the evidence of an association of RES with some migraine features partially provoked by the parasympathetic system supports the hypothesis of a shared pathophysiological background (e.g. via the activation of the trigeminal-autonomic reflex).
Persistent Disability Despite Sufficient Calf Muscle Strength After Rerupture of Surgically Treated Acute Achilles Tendon Ruptures
Authors: Metz Roderik , van der Heijden Geert J. M. G. , Verleisdonk Egbert-Jan M. M. , Andrlik Milan , van der Werken Christiaan 
Published: December 2010

Rerupture after treatment of acute Achilles tendon rupture is considered a serious complication. Yet data on long-term outcome after rerupture are limited. This study evaluated outcome after rerupture and compares it to a reference of uncomplicated cases. Thirteen patients with a rerupture following minimally invasive surgical Achilles tendon rupture repair were evaluated using Leppilahti score and resumption of work and sport. Mean follow-up was 8.7 years. Results were compared with a reference group of 23 uncomplicated cases with a follow-up of at least 1 year. The study was designed as a follow-up study. The relative risk for a fair/poor outcome by Leppilahti score after a rerupture when compared with uncomplicated cases is 2.83 (95% confidence interval = 1.17-6.87; P = .0185). Although rerupture did not affect ultimate resumption of professional life, the relative risk for quitting sport or resuming sport at a lower level after a rerupture is 3.33 (95% confidence interval = 1.71-6.51; P = .0001). In contrast, the plantar flexion strength deficit is 5% to 10% in the rerupture group and up to 20% in the reference group. Despite sufficient recovery of calf muscle strength, rerupture after acute Achilles tendon rupture treatment results in significant long-term functional disabilities. Level of Evidence: Prognostic, Level II
dbDEMC: a database of differentially expressed miRNAs in human cancers
Authors: Yang Zhen , Ren Fei , Liu Changning , He Shunmin , Sun Gang , Gao Qian , Yao Lei , Zhang Yangde , Miao Ruoyu , Cao Ying , Zhao Yi , Zhong Yang , Zhao Haitao 
Published: December 2010

Abstract

Background
MicroRNAs (miRNAs) are small noncoding RNAs about 22 nt long that negatively regulate gene expression at the post-transcriptional level. Their key effects on various biological processes, e.g., embryonic development, cell division, differentiation and apoptosis, are widely recognized. Evidence suggests that aberrant expression of miRNAs may contribute to many types of human diseases, including cancer. Here we present a database of differentially expressed miRNAs in human cancers (dbDEMC), to explore aberrantly expressed miRNAs among different cancers.

Results
We collected the miRNA expression profiles of 14 cancer types, curated from 48 microarray data sets in peer-reviewed publications. The Significance Analysis of Microarrays method was used to retrieve the miRNAs that have dramatically different expression levels in cancers when compared to normal tissues. This database provides statistical results for differentially expressed miRNAs in each data set. A total of 607 differentially expressed miRNAs (590 mature miRNAs and 17 precursor miRNAs) were obtained in the current version of dbDEMC. Furthermore, low-throughput data from the same literature were also included in the database for validation. An easy-to-use web interface was designed for users. Annotations about each miRNA can be queried through miRNA ID or miRBase accession numbers, or can be browsed by different cancer types.

Conclusions
This database is expected to be a valuable source for identification of cancer-related miRNAs, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. All the information is freely available through http://159.226.118.44/dbDEMC/index.html.
Apoptosis of non-parasitized red blood cells in malaria: a putative mechanism involved in the pathogenesis of anaemia
Authors: Totino Paulo RR , Magalhães Aline D , Silva Luciene A , Banic Dalma M , Daniel-Ribeiro Cláudio T , Ferreira-da-Cruz Maria de Fátima 
Published: December 2010

AbstractBackgroundSevere anaemia is a common complication ofPlasmodium falciparummalaria in hyperendemic regions. Premature elimination of non-parasitized red blood cells (nRBC) has been considered as one mechanism involved in the genesis of severe malaria anaemia. It has been reported that apoptosis can occur in RBC and, consequently, this cell death process could contribute to anaemia. This study was performed to evaluate the susceptibility of nRBC to apoptosis in a malaria anaemia murine model.MethodsBalb/c mice were intraperitonially inoculated with 1 × 106P. yoelii17XL parasitized RBC (pRBC) and, then, parasitaemia and anaemia were monitored. Apoptosis in both pRBC and nRBC was assessed during early and late phases of infection by flow cytometry using Syto 16 and annexin V-PE double staining and forward scatter measurement.ResultsAs expected, experimental infection of Balb/c mice withPlasmodium yoelii17XL parasites was characterized by progressive increase of parasitaemia and acute anaemia, leading to death. Flow cytometry analysis showed that a number of pRBC was in the apoptotic process. It was noteworthy that the increase of nRBC apoptosis levels occurred in the late phase of infection, when anaemia degree was notably accentuated, while no significant alteration was observed in the early phase.ConclusionThe increased levels of nRBC apoptosis herein firstly reported, in malaria infection could represent a putative mechanism worsening the severity of malarial anaemia.