bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Analysis of Tuberous Sclerosis Complex Cortical Tubers Reveals Increased Expression of Adhesion and Inflammatory Factors
Authors: Boer Karin , Crino Peter B. , Gorter Jan A. , Nellist Mark , Jansen Floor E. , Spliet Wim G.M. , Van Rijen Peter C. , Wittink Floyd R.A. , Breit Timo M. , Troost Dirk , Wadman Wytse J. , Aronica Eleonora 
Published: October 2009

AbstractCortical tubers in patients with tuberous sclerosis complex are associated with disabling neurological manifestations, including intractable epilepsy. While these malformations are believed to result from the effects ofTSC1orTSC2gene mutations, the molecular mechanisms leading to tuber formation, as well as the onset of seizures, remain largely unknown. We used the Affymetrix Gene Chip platform to provide the first genome‐wide investigation of gene expression in surgically resected tubers, compared with histological normal perituberal tissue from the same patients or autopsy control tissue. We identified 2501 differentially expressed genes in cortical tubers compared with autopsy controls. Expression of genes associated with cell adhesion, for example,VCAM1,integrinsandCD44, or with the inflammatory response, including complement factors,serpinA3,CCL2and several cytokines, was increased in cortical tubers, whereas genes related to synaptic transmission, for example, the glial glutamate transporterGLT‐1, and voltage‐gated channel activity, exhibited lower expression. Gene expression in perituberal cortex was distinct from autopsy control cortex suggesting that even in the absence of tissue pathology the transcriptome is altered in TSC. Changes in gene expression yield insights into new candidate genes that may contribute to tuber formation or seizure onset, representing new targets for potential therapeutic development.
Diabetic macular oedema and visual loss: relationship to location, severity and duration
Authors: Gardner Thomas W. , Larsen Michael , Girach Aniz , Zhi Xin ,   on behalf of the Protein Kinase C Diabetic Retinopathy Study (PKC‐DRS2) Study Group
Published: October 2009

Abstract.Purpose:  To assess the relationship between visual acuity (VA) and diabetic macular oedema (DMO) in relation to the location of retinal thickening and the severity and duration of central macular thickening.Methods:  Data from 584 eyes in 340 placebo‐treated patients in the 3‐years‐long Protein Kinase C Diabetic Retinopathy Study (PKC‐DRS2) trial were used to investigate the relationship between VA and DMO. Eligible eyes had moderately severe to very severe non‐proliferative diabetic retinopathy and VA of at least 45 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) charts (Snellen equivalent = 20/125). Diabetic retinopathy and DMO status were assessed using stereo photographs.Results:  Nearly one third of study eyes had foveal centre‐involving DMO at the start of the trial. Sustained moderate visual loss was found in 36 eyes, most commonly associated with DMO at the centre of the fovea in 73% of eyes. There was a strong relationship (p < 0.001) between foveal centre involvement with DMO and mean VA. Mean VA decreased with increasing retinal thickness at the centre (p < 0.001) and increasing duration of centre‐involving DMO (p < 0.001).Conclusion:  This study documents the relationship between duration of DMO and progressive vision loss, and the key role of central foveal involvement in patients with diabetic retinopathy. These data will help to develop future strategies to prevent vision loss.
The microbial methane cycle
Authors: Murrell J. Colin , Jetten Mike S. M. 
Published: October 2009

SummaryThis special issue highlights several recent discoveries in the microbial methane cycle, including the diversity and activity of methanotrophic bacteria in special habitats, distribution and contribution of the newly discovered Verrucomicrobia, metabolism of methane and related one‐carbon compounds such as methanol and methylamine in freshwater and marine environments, methanol and methane‐dependent nitrate reduction, the relationships of methane cycle microorganisms with plants and animals, and the environmental factors that regulate microbial processes of the methane cycle. These articles also highlight the plethora of new organisms and metabolism relating to the methane cycle that have been discovered in recent years and outline the many questions in the methane cycle that still need to be addressed. It is clear that despite a tremendous amount of research on the biology of the methane cycle, the microbes involved in catalysing methane production and consumption harbour many secrets that need to be disclosed in order for us to fully understand how the biogeochemical methane cycle is regulated in the environment, and for us to make future predictions about the global sources and sinks of methane and how anthropogenic changes impact on the cycling of this important greenhouse gas.
Population Structure of
Staphylococcus aureus
Strains Isolated from Intensive Care Unit Patients in The Netherlands over an 11-Year Period (1996 to 2006)
Authors: Rijnders M. I. A. , Deurenberg R. H. , Boumans M. L. L. , Hoogkamp-Korstanje J. A. A. , Beisser P. S. , Stobberingh E. E. 
Published: October 2009

ABSTRACT

The genetic background and the presence of several virulence factors of
Staphylococcus aureus
isolates from intensive care unit (ICU) patients from 14 hospitals in The Netherlands isolated from 1996 until 2006 were investigated. In total, 936 methicillin-susceptible
S. aureus
(MSSA) and 7 methicillin-resistant
S. aureus
(MRSA) isolates were collected. The genetic background was determined by
spa
typing and multilocus sequence typing (MLST). The virulence determinants Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), and collagen adhesion (CNA) were detected with real-time PCR assays. On the MRSA isolates, mobile resistance staphylococcal cassette chromosome
mec
(SCC
mec
) typing was performed. Among the MSSA isolates, 313 different
spa
types were observed. A genetic background common to MRSA clones, e.g., MLST clonal complex 1 (CC1), CC5, CC8, CC22, CC30, and CC45, was observed among 62% of the isolates. The remaining isolates were associated with MSSA-related MLST CCs. MLST CC1, CC25, and CC30 were continuously present, and other MLST CCs fluctuated over time. Two percent of the MSSA isolates harbored PVL, 21% had TSST-1, and 46% were positive for CNA. There were no changes in the prevalence of the virulence factors over time. Four MRSA isolates were typed as ST8-MRSA-IV (where ST is the MLST sequence type and IV is the SCC
mec
type), two were ST5-MRSA-II, and one was ST228-MRSA-I. All MRSA isolates were PVL, CNA, and TSST-1 negative except for the two ST5-MRSA-II isolates, which were TSST-1 positive. No changes in the
S. aureus
genetic background and the prevalence of the virulence factors PVL, CNA, and TSST-1 were observed in ICU patients in The Netherlands over time.
Infective Endocarditis Due to
Citrobacter koseri
in an Immunocompetent Adult
Authors: Dzeing-Ella A. , Szwebel T. A. , Loubinoux J. , Coignard S. , Bouvet A. , Le Jeunne C. , Aslangul E. 
Published: October 2009

ABSTRACT

Citrobacter koseri
(formerly
C
itrobacter
diversus
) is a motile gram-negative bacillus usually arising from urinary and gastrointestinal tracts.
C. koseri
rarely causes infection in immunocompetent patients and, thus far, has been considered an opportunistic pathogen. We report on a 30-year-old man, with no medical past, hospitalized for infective aortic endocarditis due to
C. koseri
. Four weeks of antibiotherapy led to a full recovery for this patient. However, this case is unusual, as previous history and 1 year of follow-up showed no features of intercurrent immunosuppression. Microbiological diagnosis was based on using 16S rRNA gene sequencing.
Acquisition of High-Level Mupirocin Resistance and Its Fitness Cost among Methicillin-Resistant
Staphylococcus aureus
Strains with Low-Level Mupirocin Resistance
Authors: Mongkolrattanothai Kanokporn , Pumfrey Lisa , Mankin Peggy , Gray Barry M. 
Published: October 2009

ABSTRACT

We investigated whether methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) isolates with low-level mupirocin resistance can serve as recipients of a pSK41-like plasmid conferring high-level mupirocin resistance without substantial fitness cost. Our results suggest that acquisition of the plasmid conferring high-level mupirocin resistance was not necessarily associated with fitness cost in some MRSA recipients with low-level mupirocin resistance.
Prevalence of ST9 Methicillin-Resistant
Staphylococcus aureus
among Pigs and Pig Handlers in Malaysia
Authors: Neela Vasanthakumari , Mohd Zafrul Arif , Mariana Nor Shamsudin , van Belkum Alex , Liew Yun Khoon , Rad Ehsanollah Ghaznavi 
Published: October 2009

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) of sequence type 398 (ST398) has frequently been detected in pigs and pig handlers. However, in Malaysia, sampling 360 pigs and 90 pig handlers from 30 farms identified novel ST9-
spa
type t4358-staphylococcal cassette chromosome
mec
type V MRSA strains that were found to transiently colonize more than 1% of pigs and 5.5% of pig handlers.
Evaluation of Three Commercial Broth Media for Pigment Detection and Identification of a Group B
Streptococcus
(
Streptococcus agalactiae
)
Authors: Carvalho Maria da Glória , Facklam Richard , Jackson Delois , Beall Bernard , McGee Lesley 
Published: October 2009

ABSTRACT

Detection of group B
Streptococcus
(GBS) strains at various bacterial concentrations was evaluated using three pigment-producing broth media. At 10
3
CFU/ml, StrepB carrot broth (SBCB), Granada instant liquid biphasic (IGLB), and Northeast Laboratory GBS screening medium (NEL-GBS) showed 100% detection, but at the lower bacterial counts, SBCB and IGLB were more sensitive than NEL-GBS after 24 h.
First Descriptions of
bla
KPC
in
Raoultella
spp. (
R. planticola
and
R. ornithinolytica
): Report from the SENTRY Antimicrobial Surveillance Program
Authors: Castanheira Mariana , Deshpande Lalitagauri M. , DiPersio Joseph R. , Kang Julia , Weinstein Melvin P. , Jones Ronald N. 
Published: October 2009

ABSTRACT

Two strains of
Raoultella planticola
and one of
Raoultella ornithinolytica
showing carbapenem resistance were recovered from patients hospitalized in New Jersey and Ohio. All patients had received previous antimicrobial treatment, including carbapenems. These strains harbored
bla
KPC-2
and
bla
KPC-3
. Carbapenemase genes were embedded in isoforms of Tn
4401
and were plasmidic and chromosomal in location.
Hemagglutinin-Dependent Tropism of H5N1 Avian Influenza Virus for Human Endothelial Cells
Authors: Ocaña-Macchi Manuela , Bel Michael , Guzylack-Piriou Laurence , Ruggli Nicolas , Liniger Matthias , McCullough Kenneth C. , Sakoda Yoshihiro , Isoda Norikazu , Matrosovich Mikhail , Summerfield Artur 
Published: October 2009

ABSTRACT
Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multiorgan failure. This is in contrast with the situation with human influenza viruses, which in immunocompetent individuals usually cause only a respiratory disease which is less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study, we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV than to infection by human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It was also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E-selectin and P-selectin were upregulated, and the proinflammatory cytokines interleukin-6 and beta interferon were secreted. H5N1 virus infection was also associated with an elevated rate of cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells that is different from human influenza viruses, and this H5N1 receptor specificity could contribute to disease pathogenesis.
Binding of Herpes Simplex Virus Glycoprotein B (gB) to Paired Immunoglobulin-Like Type 2 Receptor α Depends on Specific Sialylated O
-
Linked Glycans on gB
Authors: Wang Jing , Fan Qing , Satoh Takeshi , Arii Jun , Lanier Lewis L. , Spear Patricia G. , Kawaguchi Yasushi , Arase Hisashi 
Published: October 2009

ABSTRACT

Paired immunoglobulin-like type 2 receptor α (PILRα) is an inhibitory receptor expressed on both hematopoietic and nonhematopoietic cells. Its binding to a cellular ligand, CD99, depends on the presence of sialylated O
-
linked glycans on CD99. Glycoprotein B (gB) of herpes simplex virus type 1 (HSV-1) binds to PILRα, and this association is involved in HSV-1 infection. Here, we found that the presence of sialylated O
-
glycans on gB is required for gB to associate with PILRα. Furthermore, we identified two threonine residues on gB that are essential for the addition of the principal O
-
glycans acquired by gB and that are also essential for the binding of PILRα to gB.
The Canine Papillomavirus E5 Protein Signals from the Endoplasmic Reticulum
Authors: Condjella Rachel , Liu Xuefeng , Suprynowicz Frank , Yuan Hang , Sudarshan Sawali , Dai Yuhai , Schlegel Richard 
Published: October 2009

ABSTRACT

The recently discovered
Canis familiaris
papillomavirus (PV) type 2 (CfPV2) provides a unique opportunity to study PV gene functions in vitro and in vivo. Unlike the previously characterized canine oral PV, CfPV2 contains an E5 open reading frame and is associated with progression to squamous cell carcinoma. In the current study, we have expressed and characterized the CfPV2-encoded E5 protein, a small, hydrophobic, 41-amino-acid polypeptide. We demonstrate that, similar to the E5 protein from high-risk human PV type 16, the CfPV2 E5 protein is localized in the endoplasmic reticulum (ER) and that its expression decreases keratinocyte proliferation and cell life span. E5 expression also increases the percentage of cells in the G
1
phase of the cell cycle, with a concomitant decrease in the percentage of cells in S phase. To identify a potential mechanism for E5-mediated growth inhibition from the ER, we developed a real-time PCR method to quantify the splicing of XBP1 mRNA as a measure of ER stress. We found that the CfPV2 E5 protein induced ER stress and that this, as well as the observed growth inhibition, is tempered significantly by coexpression of the CfPV2 E6 and E7 genes. It is possible that the spatial/temporal regulation of E6/E7 gene expression during keratinocyte differentiation might therefore modulate E5 activity and ER stress.
Hepatitis C Virus (HCV) Proteins Induce NADPH Oxidase 4 Expression in a Transforming Growth Factor β-Dependent Manner: a New Contributor to HCV-Induced Oxidative Stress
Authors: Boudreau Howard E. , Emerson Suzanne U. , Korzeniowska Agnieszka , Jendrysik Meghan A. , Leto Thomas L. 
Published: October 2009

ABSTRACTViral hepatitis-induced oxidative stress accompanied by increased levels of transforming growth factor β (TGF-β) and hepatic fibrosis are hallmarks of hepatitis C virus (HCV) infection. The mechanisms of redox regulation in the pathogenesis of HCV-induced liver disease are not clearly understood. The results of our current studies suggest that reactive oxygen species (ROS) derived from Nox4, a member of the NADPH oxidase (Nox) family, could play a role in HCV-induced liver disease. We found that the expression of HCV (genotype 1a) cDNA constructs (full-length and subgenomic), core protein alone, viral RNA, or replicating HCV (JFH-AM2) induced Nox4 mRNA expression and ROS generation in human hepatocyte cell lines (Huh-7, Huh-7.5, HepG2, and CHL). Conversely, hepatocytes expressing Nox4 short hairpin RNA (shRNA) or an inactive dominant negative form of Nox4 showed decreased ROS production when cells were transfected with HCV. The promoters of both human and murine Nox4 were used to demonstrate transcriptional regulation of Nox4 mRNA by HCV, and a luciferase reporter tied to an ∼2-kb promoter region of Nox4 identified HCV-responsive regulatory regions modulating the expression of Nox4. Furthermore, the human Nox4 promoter was responsive to TGF-β1, and the HCV core-dependent induction of Nox4 was blocked by antibody against TGF-β or the expression of dominant negative TGF-β receptor type II. These findings identified HCV as a regulator of Nox4 gene expression and subsequent ROS production through an autocrine TGF-β-dependent mechanism. Collectively, these data provide evidence that HCV-induced Nox4 contributes to ROS production and may be related to HCV-induced liver disease.
Early, Active, and Specific Localization of Herpes Simplex Virus Type 1 gM to Nuclear Membranes
Authors: Zhang Jie , Nagel Claus-Henning , Sodeik Beate , Lippé Roger 
Published: October 2009

ABSTRACT

Thirteen different glycoproteins are incorporated into mature herpes simplex virus type 1 (HSV-1) virions. Five of them play important roles during entry, while others intervene during egress of the virus. Although HSV-1 gM is not essential in cell culture, its deletion reduces viral yields and promotes syncytium formation. Furthermore, gM is conserved among herpesviruses, is essential for several of them, and can redirect the gD and gH/gL viral glycoproteins from the cell surface to the
trans
-Golgi network, where gM presumably modulates final capsid envelopment. Late in infection, gM reaches the nuclear envelope and decorates perinuclear virions. This process seemingly requires U
L
31 and U
L
34 and occurs when several markers of the
trans
-Golgi network have relocalized to the nucleus. However, the precise mechanism of gM nuclear targeting is unclear. We now report that gM is quickly and specifically targeted to nuclear membranes in a virus-dependent manner. This occurs prior to the HSV-1-induced reorganization of the
trans
-Golgi network and before gM enters the secretory pathway. The presence of a high-mannose glycosylation pattern on gM further corroborated these findings. While gM was targeted to the inner nuclear membrane early in infection, its partners gD, gH, gN, VP22, U
L
31, and U
L
34 did not colocalize with gM. These data suggest that nuclear gM fulfills an early nuclear function that is independent of its known interaction partners and its function in viral egress.
Characterization of Viral and Human RNAs Smaller than Canonical MicroRNAs
Authors: Li Zhihua , Kim Sang Woo , Lin Yuefeng , Moore Patrick S. , Chang Yuan , John Bino 
Published: October 2009

ABSTRACT

Recently identified small (20 to 40 bases) RNAs, such as microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) participate in important cellular pathways. In this report, we systematically characterized several novel features of human and viral RNA products smaller than miRNAs. We found that Kaposi sarcoma-associated herpesvirus K12-1 miRNA (23 bases) associates with a distinct, unusually small (17-base) RNA (usRNA) that can effectively downregulate a K12-1 miRNA target, human
RAD21
, suggesting that stable degradation-like products may also contribute to gene regulation. High-throughput sequencing reveals a diverse set of human miRNA-derived usRNAs and other non-miRNA-derived usRNAs. Human miRNA-derived usRNAs preferentially match to 5′ ends of miRNAs and are also more likely to associate with the siRNA effector protein Ago2 than with Ago1. Many non-miRNA-derived usRNAs associate with Ago proteins and also frequently contain C-rich 3′-specific motifs that are overrepresented in comparison to Piwi-interacting RNAs and transcription start site-associated RNAs. We postulate that approximately 30% of usRNAs could have evolved to participate in biological processes, including gene silencing.
A New Genetic Vaccine Platform Based on an Adeno-Associated Virus Isolated from a Rhesus Macaque
Authors: Lin Jianping , Calcedo Roberto , Vandenberghe Luk H. , Bell Peter , Somanathan Suryanarayan , Wilson James M. 
Published: October 2009

ABSTRACT

We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8
+
T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8
+
T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses.
High Frequencies of Virus-Specific CD8+T-Cell Precursors
Authors: Seedhom Mina O. , Jellison Evan R. , Daniels Keith A. , Welsh Raymond M. 
Published: October 2009

ABSTRACTA productive CD8+T-cell response to a viral infection requires rapid division and proliferation of virus-specific CD8+T cells. Tetramer-based enrichment assays have recently given estimates of the numbers of peptide-major histocompatibility complex-specific CD8+T cells in naïve mice, but precursor frequencies for entire viruses have been examined only by using in vitro limiting-dilution assays (LDAs). To examine CD8+T-cell precursor frequencies for whole viruses, we developed an in vivo LDA and found frequencies of naïve CD8+T-cell precursors of 1 in 1,444 for vaccinia virus (VV) (∼13,850 VV-specific CD8+T cells per mouse) and 1 in 2,958 for lymphocytic choriomeningitis virus (LCMV) (∼6,761 LCMV-specific CD8+T cells per mouse) in C57BL/6J mice. In mice immune to VV, the number of VV-specific precursors, not surprisingly, dramatically increased to 1 in 13 (∼1,538,462 VV-specific CD8+T cells per mouse), consistent with estimates of VV-specific memory T cells. In contrast, precursor numbers for LCMV did not increase in VV-immune mice (1 in 4,562, with ∼4,384 LCMV-specific CD8+T cells per VV-immune mouse). Using H-2Db-restricted LCMV GP33-specific P14-transgenic T cells, we found that, after donor T-cell take was accounted for, approximately every T cell transferred underwent a full proliferative expansion in response to LCMV infection. This high efficiency was also seen with memory populations, suggesting that most antigen-specific T cells will proliferate extensively at a limiting dilution in response to infections. These results show that frequencies of naïve and memory CD8+T cell precursors for whole viruses can be remarkably high.