bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microvascular retinopathy in subjects without diabetes: the Inter99 Eye Study
Authors: Munch Inger Christine , Kessel Line , Borch‐Johnsen Knut , Glümer Charlotte , Lund‐Andersen Henrik , Larsen Michael 
Published: April 2011

Abstract.Purpose:  Retinal vascular lesions such as microaneurysms and haemorrhages, while typical of diabetic retinopathy, are also seen in subjects without diabetes where they are associated with elevated cardiovascular mortality. In theory, these lesions could be a consequence of past hyperglycaemia. We examined the prevalence and risk factors for retinopathy, including lens fluorescence, a biomarker of cumulative life‐time glycaemia in adults without diabetes.Methods:  Cross‐sectional population‐based study of 711 subjects without diabetes (WHO 1999 criteria) aged 30–60 years, including oral glucose tolerance testing, clinical and laboratory examinations, non‐invasive ocular lens fluorometry and seven‐field fundus photography.Results:  Retinopathy was present in 8.3% (CI95 6.3–10.3%) of subjects. Higher systolic blood pressure (SBP) (p = 0.032), increasing body mass index (BMI) (p = 0.014) and wider waist circumference (p = 0.014) were significantly associated with retinopathy after adjusting for age and sex. Retinopathy was not significantly related to long‐term, short‐term or current glycaemia (lens fluorescence, HbA1c, fasting plasma glucose). In the multivariate analysis, the odds ratio (OR) for retinopathy in subjects with SBP ≥160 mmHg compared to subjects with SBP <130 mmHg was 2.68 (CI95 1.07–6.70, p = 0.036) and in subjects with BMI ≥30 compared to subjects with BMI < 25 the OR for retinopathy was 2.14 (CI95 1.01–4.57, p = 0.049) when adjusting for both variables, age, sex, the presence of impaired glucose tolerance and impaired fasting glucose.Conclusion:  Retinopathy in subjects without diabetes was associated with hypertension and obesity. The study found no evidence that microvascular retinopathy in non‐diabetic subjects was a consequence of past hyperglycaemia.
Explaining How the Mind Works: On the Relation Between Cognitive Science and Philosophy
Authors: Trigg Jonathan , Kalish Michael 
Published: April 2011

AbstractIn this paper, we argue that under certain prevalent interpretations of the nature and aims of cognitive science, theories of cognition generate a forced choice between a conception of cognition which depends on the possibility of a private language, and a conception of cognition which depends on mereological confusions. We argue, further, that this should not pose a fundamental problem for cognitive scientists since a plausible interpretation of the nature and aims of cognitive science is available that does not generate this forced choice. The crucial difference between these interpretations is that on the one hand the aim of theories of cognition is to tell us what thinking (etc.) is, and on the other it is to tell us what is causally necessary if an intelligent creature is to be able to think. Our argument draws heavily on a Wittgensteinian conception of philosophy in which no philosophical theory can explain what thinking, perceiving, remembering, etc. are, either. The positive, strictly therapeutic, purpose of a philosophy of cognitive science should be to show that, since the traditional problems which constitute the philosophy of mind are chimerical, there is nothing for philosophical theorizing in cognitive science to achieve.
Philosophy for the Rest of Cognitive Science
Authors: Stepp Nigel , Chemero Anthony , Turvey Michael T. 
Published: April 2011

AbstractCognitive science has always included multiple methodologies and theoretical commitments. The philosophy of cognitive science should embrace, or at least acknowledge, this diversity. Bechtel’s (2009a) proposed philosophy of cognitive science, however, applies only to representationalist and mechanist cognitive science, ignoring the substantial minority of dynamically oriented cognitive scientists. As an example of nonrepresentational, dynamical cognitive science, we describe strong anticipation as a model for circadian systems (Stepp & Turvey, 2009). We then propose a philosophy of science appropriate to nonrepresentational, dynamical cognitive science.
Retinoic Acid and α-Galactosylceramide Differentially Regulate B Cell ActivationIn Vitroand Augment Antibody ProductionIn Vivo
Authors: Chen Qiuyan , Mosovsky Kara L. , Ross A. Catharine 
Published: April 2011

ABSTRACTAll-trans-retinoic acid (RA) promotes the maturation and differentiation of B cells, which are known as a type of professional antigen-presenting cells. We show here that CD1d, a major histocompatibility complex class I-like molecule that presents lipid antigens, is expressed in the mouse spleen B cells and is increased by RA. Thus, we hypothesized that RA and the CD1d ligand, α-galactosylceramide (αGalCer), could interact to promote the differentiation, maturation, and antibody response of antigen-activated B cells. In isolated B cells, αGalCer alone markedly stimulated, and RA further increased B cell proliferation, synergizing with the B cell antigen receptor ligation via anti-μ antibody (P< 0.05). The significantly increased cell proliferation stimulated by αGalCer was abrogated in the B cells of CD1d-null mice. RA alone and combined with αGalCer also promoted B cell differentiation by the enrichment of sIgG1-, CD138-, and PNA/Fas-positive B cells (P< 0.05), suggesting a plasmacytic cell differentiation.In vivo, wild-type mice treated with RA and/or αGalCer during primary immunization with tetanus toxoid produced a higher serum anti-tetanus IgG response and had more bone marrow anti-tetanus antibody-secreting cells as determined by enzyme-linked immunospot assay (P< 0.05) in the secondary response, a finding indicative of heightened long-term memory; however, the increased antibody secretion after αGalCer treatment was abolished in CD1d-null mice. We provide evidence here that RA, together with αGalCer, can effectively regulate B cell proliferation and differentiation, ultimately promoting a more efficient antibody response to protein antigen. The results suggest that the combination of RA and αGalCer could be a useful adjuvant combination in vaccine strategies.
Sensitivity and Specificity of Serologic Assays for Detection of Human Infection with 2009 Pandemic H1N1 Virus in U.S. Populations
Authors: Veguilla Vic , Hancock Kathy , Schiffer Jarad , Gargiullo Paul , Lu Xiuhua , Aranio Darbi , Branch Alicia , Dong Libo , Holiday Crystal , Liu Feng , Steward-Clark Evelene , Sun Hong , Tsang Byron , Wang David , Whaley Melissa , Bai Yaohui , Cronin Li , Browning Peter , Dababneh Hanan , Noland Heather , Thomas Leilani , Foster Lydia , Quinn Conrad P. , Soroka Stephen D. , Katz Jacqueline M. 
Published: April 2011

ABSTRACT
Swine origin 2009 H1N1 influenza virus has spread globally to cause the first influenza pandemic of the 21st century. Serological studies can improve our understanding of the extent of human infection and risk factors associated with the transmission of this pandemic virus. The “gold standard” for serodiagnosis of human influenza virus infection is the detection of seroconversion between acute- and convalescent-stage samples. However, the timing of seroepidemiological investigations often precludes the collection of truly acute-phase sera, requiring development of serological criteria for evaluating convalescent-phase sera that optimize detection of true positives and true negatives. To guide seroepidemiological investigations into the spread of the novel 2009 pandemic H1N1 virus, we characterized serum antibody responses to 2009 H1N1 virus in 87 individuals with confirmed viral infection and 227 nonexposed U.S. individuals using microneutralization (MN) and hemagglutination inhibition (HI) assays. Sensitivity and specificity were determined for each assay alone and in combination for detection of 2009 H1N1 virus-specific antibodies in convalescent-phase sera. Although the HI assay was more specific for detecting antibody to 2009 H1N1, the MN assay was more sensitive, particularly for detecting low-titer seroconversions. A combination of titers (MN ≥ 40 and HI ≥ 20) provided the highest sensitivity (90%) and specificity (96%) for individuals aged <60 years and 92% specificity for adults aged ≥60 years for detection of serologically confirmed 2009 H1N1 infections in U.S. populations during the first pandemic waves. These studies provide an approach to optimize timely serological investigations for future pandemics or outbreaks of novel influenza viruses among humans.
Amplified Fragment Length Polymorphism Reveals Specific Epigenetic Distinctions between Mycobacterium avium Subspecies paratuberculosis Isolates of Various Isolation Types
Authors: O'Shea B. , Khare S. , Klein P. , Roussel A. , Adams L. G. , Ficht T. A. , Rice-Ficht A. C. 
Published: April 2011

ABSTRACT

Amplified fragment length polymorphism (AFLP) was employed as a genetic analysis tool for the study of the genetic relatedness of
Mycobacterium avium
subsp.
paratuberculosis
isolates harvested from bovine fecal samples and from bovine or human tissues. This analysis revealed genetic differences between these two isolate types that were confirmed through cluster analysis. Dendrogram analysis separated these two isolate types based on the isolation scheme (tissue-associated versus fecal
M. avium
subsp.
paratuberculosis
isolates). Further sequence analysis of unique genetic regions from each isolation type revealed no genetic sequence differences. However, Clustal DNA alignments identified AFLP restriction enzyme sites that were undigested in the tissue-associated isolates. AFLP analysis also disclosed that the same AFLP restriction sites were digested in all of the fecal isolates. Sequence analysis further revealed a consensus sequence upstream of the undigested restriction sites for possible methyltransferase recognition in the tissue-associated
M. avium
subsp.
paratuberculosis
isolates.
Rapid Differentiation of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus by Flow Cytometry after Brief Antibiotic Exposure
Authors: Shrestha Nabin K. , Scalera Nikole M. , Wilson Deborah A. , Procop Gary W. 
Published: April 2011

ABSTRACT

We noticed that methicillin-resistant
Staphylococcus aureus
(MRSA) and methicillin-susceptible
S. aureus
(MSSA) isolates yielded side-scatter (SSC) and fluorescence intensity (FI) differences on flow cytometry (FCM) following incubation in oxacillin broth. The purpose of this study was to determine whether MRSA and MSSA could be reliably differentiated by FCM.
S. aureus
isolates were incubated in oxacillin-containing Mueller-Hinton broth, stained using the FASTEST total viable organisms kit, and analyzed by FCM in the MicroPRO instrument. SSC versus FI were examined, and gates 1 and 2 were defined to encompass the majority of MSSA and MRSA signal events, respectively. A count ratio (CR) was defined as the ratio of counts in gate 2 to those in gate 1. Initially, 33 isolates were tested after 4 h of incubation for proof-of-concept. Twenty others were then tested after incubation intervals ranging from 30 min to 4 h to determine the earliest possible time for differentiation. Next, 100 separate isolates were tested to determine the best CR cutoff value. Finally, the CR was validated by using an independent cohort of 121 isolates. We noted that MRSA isolates had higher SSC and FI readings than did MSSA isolates after 2 h of incubation. The receiver-operator characteristics curve showed that a CR cutoff of 0.0445 reliably differentiated MRSA from MSSA. In the validation cohort, this cutoff had a sensitivity of 100% and a specificity of 98.7% for identifying MRSA from among
S. aureus
isolates, following 2 h of incubation. This study demonstrates that MRSA and MSSA can be accurately differentiated by FCM after 2 h of incubation in an oxacillin-containing liquid culture medium.
Complexity and Catalytic Efficiency of Hepatitis C Virus (HCV) NS3 and NS4A Protease Quasispecies Influence Responsiveness to Treatment with Pegylated Interferon plus Ribavirin in HCV/HIV-Coinfected Patients
Authors: Aparicio Ester , Franco Sandra , Parera Mariona , Andrés Cristina , Tural Cristina , Clotet Bonaventura , Martínez Miguel Angel 
Published: April 2011

ABSTRACT

The role of the hepatitis C virus (HCV) NS3/4A protease in ablating the signaling pathway involved in the production of alpha/beta interferon (IFN-α/β) suggests a relationship between NS3/4A proteolytic activity and a patient's response to IFN-based therapy. To identify viral factors associated with the HCV treatment response, we analyzed the pretreatment NS3/4A protease gene quasispecies composition of 56 HCV genotype 1–HIV-1-coinfected patients treated in our clinic with pegylated IFN (pegIFN) plus ribavirin (RBV). The catalytic efficiency of the dominant (i.e., the most abundant) quasispecies was also assayed for Cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower Shannon entropy values were detected within the responder group (
P
< 0.05). A correlation was also found between the efficiency of NS3/4A protease Cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing Cardif (mean ± standard error of the mean [SEM], 0.8960 ± 0.05568;
n
= 19) than proteases from nonresponders (mean ± SEM, 0.7269 ± 0.05306;
n
= 37;
P
< 0.05). Finally, the amino acid p distance (the proportion [p] of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28B (IL-28B) risk allele (
P
< 0.01), suggesting that IL-28B risk allele carriers exert a lower positive selection pressure on the NS3/4A protease. NS3/4A protease efficiency in cleaving Cardif may be associated with the pegIFN-RBV treatment response, as shown in our cohort of HIV-HCV-coinfected patients. Greater NS3/4A nucleotide heterogeneity and higher Shannon entropy values in nonresponders suggest that less HCV quasispecies complexity may favor a better response to pegIFN-RBV.
Differential Pathogenesis of Respiratory Syncytial Virus Clinical Isolates in BALB/c Mice
Authors: Stokes Kate L. , Chi Michael H. , Sakamoto Kaori , Newcomb Dawn C. , Currier Michael G. , Huckabee Matthew M. , Lee Sujin , Goleniewska Kasia , Pretto Carla , Williams John V. , Hotard Anne , Sherrill Taylor P. , Peebles R. Stokes , Moore Martin L. 
Published: April 2011

ABSTRACTAirway mucus is a hallmark of respiratory syncytial virus (RSV) lower respiratory tract illness. Laboratory RSV strains differentially induce airway mucus production in mice. Here, we tested the hypothesis that RSV strains differ in pathogenesis by screening six low-passage RSV clinical isolates for mucogenicity and virulence in BALB/cJ mice. The RSV clinical isolates induced variable disease severity, lung interleukin-13 (IL-13) levels, and gob-5 levels in BALB/cJ mice. We chose two of these clinical isolates for further study. Infection of BALB/cJ mice with RSV A2001/2-20 (2-20) resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels than infection with RSV strains A2, line 19, Long, and A2001/3-12 (3-12). Like the line 19 RSV strain, the 2-20 clinical isolate induced airway mucin expression in BALB/cJ mice. The 2-20 and 3-12 RSV clinical isolates had higher lung viral loads than laboratory RSV strains at 1 day postinfection (p.i.). This increased viral load correlated with higher viral antigen levels in the bronchiolar epithelium and greater histopathologic changes at 1 day p.i. The A2 RSV strain had the highest peak viral load at day 4 p.i. RSV 2-20 infection caused epithelial desquamation, bronchiolitis, airway hyperresponsiveness, and increased breathing effort in BALB/cJ mice. We found that RSV clinical isolates induce variable pathogenesis in mice, and we established a mouse model of clinical isolate strain-dependent RSV pathogenesis that recapitulates key features of RSV disease.
The F1 Motif of Dengue Virus Polymerase NS5 Is Involved in Promoter-Dependent RNA Synthesis
Authors: Iglesias Nestor G. , Filomatori Claudia V. , Gamarnik Andrea V. 
Published: April 2011

ABSTRACT

The mechanism by which viral RNA-dependent RNA polymerases (RdRp) specifically amplify viral genomes is still unclear. In the case of flaviviruses, a model has been proposed that involves the recognition of an RNA element present at the viral 5′ untranslated region, stem-loop A (SLA), that serves as a promoter for NS5 polymerase binding and activity. Here, we investigated requirements for specific promoter-dependent RNA synthesis of the dengue virus NS5 protein. Using mutated purified NS5 recombinant proteins and infectious viral RNAs, we analyzed the requirement of specific amino acids of the RdRp domain on polymerase activity and viral replication. A battery of 19 mutants was designed and analyzed. By measuring polymerase activity using nonspecific poly(rC) templates or specific viral RNA molecules, we identified four mutants with impaired polymerase activity. Viral full-length RNAs carrying these mutations were found to be unable to replicate in cell culture. Interestingly, one recombinant NS5 protein carrying the mutations K456A and K457A located in the F1 motif lacked RNA synthesis dependent on the SLA promoter but displayed high activity using a poly(rC) template. Promoter RNA binding of this NS5 mutant was unaffected while
de novo
RNA synthesis was abolished. Furthermore, the mutant maintained RNA elongation activity, indicating a role of the F1 region in promoter-dependent initiation. In addition, four NS5 mutants were selected to have polymerase activity in the recombinant protein but delayed or impaired virus replication when introduced into an infectious clone, suggesting a role of these amino acids in other functions of NS5. This work provides new molecular insights on the specific RNA synthesis activity of the dengue virus NS5 polymerase.
CD4
+
T Cells, Including Th17 and Cycling Subsets, Are Intact in the Gut Mucosa of HIV-1-Infected Long-Term Nonprogressors
Authors: Ciccone Emily J. , Greenwald Jamieson H. , Lee Philip I. , Biancotto Angélique , Read Sarah W. , Yao Michael A. , Hodge Jessica N. , Thompson William L. , Kovacs Stephen B. , Chairez Cheryl L. , Migueles Stephen A. , Kovacs Joseph A. , Margolis Leonid B. , Sereti Irini 
Published: April 2011

ABSTRACT

During acute human immunodeficiency virus (HIV) infection, there is a massive depletion of CD4
+
T cells in the gut mucosa that can be reversed to various degrees with antiretroviral therapy. Th17 cells have been implicated in mucosal immunity to extracellular bacteria, and preservation of this subset may support gut mucosal immune recovery. However, this possibility has not yet been evaluated in HIV-1-infected long-term nonprogressors (LTNPs), who maintain high CD4
+
T cell counts and suppress viral replication in the absence of antiretroviral therapy. In this study, we evaluated the immunophenotype and function of CD4
+
T cells in peripheral blood and gut mucosa of HIV-uninfected controls, LTNPs, and HIV-1-infected individuals treated with prolonged antiretroviral therapy (ART) (VL [viral load]<50). We found that LTNPs have intact CD4
+
T cell populations, including Th17 and cycling subsets, in the gut mucosa and a preserved T cell population expressing gut homing molecules in the peripheral blood. In addition, we observed no evidence of higher monocyte activation in LTNPs than in HIV-infected (HIV
−
) controls. These data suggest that, similar to nonpathogenic simian immunodeficiency virus (SIV) infection, LTNPs preserve the balance of CD4
+
T cell populations in blood and gut mucosa, which may contribute to the lack of disease progression observed in these patients.
Discrimination of Mumps Virus Small Hydrophobic Gene Deletion Effects from Gene Translation Effects on Virus Virulence
Authors: Malik Tahir , Shegogue Candie Wolbert , Werner Kellie , Ngo Laurie , Sauder Christian , Zhang Cheryl , Duprex William Paul , Rubin Steven 
Published: April 2011

ABSTRACT

Deletion of the small hydrophobic (SH) protein of certain paramyxoviruses has been found to result in attenuation, suggesting that the SH protein is a virulence factor. To investigate the role of the mumps virus (MuV) SH protein in virulence, multiple stop codons were introduced into the open reading frame (ORF) of a MuV molecular clone (r88-1961
SHstop
), preserving genome structure but precluding production of the SH protein. No differences in neurovirulence were seen between the wild-type and the SH
stop
viruses. In contrast, upon deletion of the SH gene, significant neuroattenuation was observed. These data indicate that the MuV SH protein is not a neurovirulence factor and highlight the importance of distinguishing gene deletion effects from protein-specific effects.
Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours
Authors: Schmitz K J , Helwig J , Bertram S , Sheu S Y , Suttorp A C , Seggewiß J , Willscher E , Walz M K , Worm K , Schmid K W 
Published: April 2011

BackgroundFor the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours.MethodsIn order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16).ResultsConcerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist.ConclusionmiRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential.