bluuebunny/crossref_metadata_2025_split huggingface dataset:
The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer–cell subsets associated with high levels of HIV-1 viremia
Authors: Brunetta Enrico , Fogli Manuela , Varchetta Stefania , Bozzo Luisa , Hudspeth Kelly L. , Marcenaro Emanuela , Moretta Alessandro , Mavilio Domenico 
Published: August 2009

Abstract
HIV-1 has developed several strategies to evade natural killer (NK)–cell antiviral functions. One of these mechanisms is the HIV-1–induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1–infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid–binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7−/CD56+) or chronic (Siglec-7−/CD56−) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone antiretroviral therapy. High frequencies of Siglec-7−/CD56+ and Siglec-7−/CD56− pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy.
Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats
Authors: Huang Jiung-Pang , Huang Shiang-Suo , Deng Jen-Ying , Hung Li-Man 
Published: August 2009

Abstract
In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R) injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules). The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ)-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau) which lead to decrease in cardiac output (CO) without changing total peripheral resistance (TPR). The phosphorylated Akt and glucose transporter 4 (GLUT 4) protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.
Extending the models for iron and sulfur oxidation in the extreme Acidophile Acidithiobacillus ferrooxidans
Authors: Quatrini Raquel , Appia-Ayme Corinne , Denis Yann , Jedlicki Eugenia , Holmes David S , Bonnefoy Violaine 
Published: August 2009

Abstract

Background

Acidithiobacillus ferrooxidans gains energy from the oxidation of ferrous iron and various reduced inorganic sulfur compounds at very acidic pH. Although an initial model for the electron pathways involved in iron oxidation has been developed, much less is known about the sulfur oxidation in this microorganism. In addition, what has been reported for both iron and sulfur oxidation has been derived from different A. ferrooxidans strains, some of which have not been phylogenetically characterized and some have been shown to be mixed cultures. It is necessary to provide models of iron and sulfur oxidation pathways within one strain of A. ferrooxidans in order to comprehend the full metabolic potential of the pangenome of the genus.

Results
Bioinformatic-based metabolic reconstruction supported by microarray transcript profiling and quantitative RT-PCR analysis predicts the involvement of a number of novel genes involved in iron and sulfur oxidation in A. ferrooxidans ATCC23270. These include for iron oxidation: cup (copper oxidase-like), ctaABT (heme biogenesis and insertion), nuoI and nuoK (NADH complex subunits), sdrA1 (a NADH complex accessory protein) and atpB and atpE (ATP synthetase F0 subunits). The following new genes are predicted to be involved in reduced inorganic sulfur compounds oxidation: a gene cluster (rhd, tusA, dsrE, hdrC, hdrB, hdrA, orf2, hdrC, hdrB) encoding three sulfurtransferases and a heterodisulfide reductase complex, sat potentially encoding an ATP sulfurylase and sdrA2 (an accessory NADH complex subunit). Two different regulatory components are predicted to be involved in the regulation of alternate electron transfer pathways: 1) a gene cluster (ctaRUS) that contains a predicted iron responsive regulator of the Rrf2 family that is hypothesized to regulate cytochrome aa
3 oxidase biogenesis and 2) a two component sensor-regulator of the RegB-RegA family that may respond to the redox state of the quinone pool.

Conclusion
Bioinformatic analysis coupled with gene transcript profiling extends our understanding of the iron and reduced inorganic sulfur compounds oxidation pathways in A. ferrooxidans and suggests mechanisms for their regulation. The models provide unified and coherent descriptions of these processes within the type strain, eliminating previous ambiguity caused by models built from analyses of multiple and divergent strains of this microorganism.
Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population
Authors: Uchida Tomohisa , Nguyen Lam Tung , Takayama Akiko , Okimoto Tadayoshi , Kodama Masaaki , Murakami Kazunari , Matsuhisa Takeshi , Trinh Tuan Dung , Ta Long , Ho Dang Quy Dung , Hoang Hoa Hai , Kishida Tetsuko , Fujioka Toshio , Moriyama Masatsugu , Yamaoka Yoshio 
Published: August 2009

Abstract

Background
The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects.

Results
The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh.

Conclusion
Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.
Direct and negative regulation of the sycO-ypkA-ypoJ operon by cyclic AMP receptor protein (CRP) in Yersinia pestis
Authors: Zhan Lingjun , Yang Lei , Zhou Lei , Li Yingli , Gao He , Guo Zhaobiao , Zhang Lianfeng , Qin Chuan , Zhou Dongsheng , Yang Ruifu 
Published: August 2009

Abstract

Background
Pathogenic yersiniae, including Y. pestis, share a type III secretion system (T3SS) that is composed of a secretion machinery, a set of translocation proteins, a control system, and six Yop effector proteins including YpkA and YopJ. The cyclic AMP receptor protein (CRP), a global regulator, was recently found to regulate the laterally acquired genes (pla and pst) in Y. pestis. The regulation of T3SS components by CRP is unknown.

Results
The sycO, ypkA and yopJ genes constitute a single operon in Y. pestis. CRP specifically binds to the promoter-proximate region of sycO, and represses the expression of the sycO-ypkA-yopJ operon. A single CRP-dependent promoter is employed for the sycO-ypkA-yopJ operon, but two CRP binding sites (site 1 and site 2) are detected within the promoter region. A CRP box homologue is found in site 1 other than site 2. The determination of CRP-binding sites, transcription start site and core promoter element (-10 and -35 regions) promotes us to depict the structural organization of CRP-dependent promoter, giving a map of CRP-promoter DNA interaction for sycO-ypkA-yopJ.

Conclusion
The sycO-ypkA-yopJ operon is under the direct and negative regulation of CRP in Y. pestis. The sycO-ypkA-yopJ promoter-proximate regions are extremely conserved in Y. pestis, Y. pseudotuberculosis and Y. enterocolitica. Therefore, data presented here can be generally applied to the above three pathogenic yersiniae.
Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage
Authors: Jeon Hyojin , Ai Jinglu , Sabri Mohamed , Tariq Asma , Shang Xueyuan , Chen Gang , Macdonald R Loch 
Published: August 2009

AbstractAbout 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment.
Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen
Authors: Calmels Nadège , Seznec Hervé , Villa Pascal , Reutenauer Laurence , Hibert Marcel , Haiech Jacques , Rustin Pierre , Koenig Michel , Puccio Hélène 
Published: August 2009

Abstract

Background
Pharmacological high-throughput screening (HTS) represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA). FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC) proteins activity, due to a partial loss of frataxin function, a mitochondrial protein proposed to function as an iron-chaperone for ISC biosynthesis. In the absence of measurable catalytic function for frataxin, a cell-based assay is required for HTS assay.

Methods
Using a targeted ribozyme strategy in murine fibroblasts, we have developed a cellular model with strongly reduced levels of frataxin. We have used this model to screen the Prestwick Chemical Library, a collection of one thousand off-patent drugs, for potential molecules for FRDA.

Results
The frataxin deficient cell lines exhibit a proliferation defect, associated with an ISC enzyme deficit. Using the growth defect as end-point criteria, we screened the Prestwick Chemical Library. However no molecule presented a significant and reproducible effect on the proliferation rate of frataxin deficient cells. Moreover over numerous passages, the antisense ribozyme fibroblast cell lines revealed an increase in frataxin residual level associated with the normalization of ISC enzyme activities. However, the ribozyme cell lines and FRDA patient cells presented an increase in Mthfd2 transcript, a mitochondrial enzyme that was previously shown to be upregulated at very early stages of the pathogenesis in the cardiac mouse model.

Conclusion
Although no active hit has been identified, the present study demonstrates the feasibility of using a cell-based approach to HTS for FRDA. Furthermore, it highlights the difficulty in the development of a stable frataxin-deficient cell model, an essential condition for productive HTS in the future.
In-vivo imaging of retinal nerve fiber layer vasculature: imaging - histology comparison
Authors: Scoles Drew , Gray Daniel C , Hunter Jennifer J , Wolfe Robert , Gee Bernard P , Geng Ying , Masella Benjamin D , Libby Richard T , Russell Stephen , Williams David R , Merigan William H 
Published: August 2009

Abstract

Background
Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed.

Methods
We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue.

Results
Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections.

Conclusion
This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma.
Modulation of expression and cellular distribution of p21 by macrophage migration inhibitory factor
Authors: Taranto Elliott , Xue Jin R , Morand Eric F , Leech Michelle 
Published: August 2009

AbstractBackgroundThe pleiotropic protein MIF, (macrophage migration inhibitory factor), has been demonstrated to modulate several key proteins governing cell cycle control and is considered to contribute to cell growth and differentiation. In this study we investigated the effect of MIF on the expression and cellular distribution of the CDK inhibitor p21.MethodsThe effect of endogenous MIF on p21 expression and distribution was examined by comparing murine dermal fibroblasts derived fromwtand MIF -/- mice. The effect of MIF on cell growth and apoptotic rates was compared using3H-Thymidine incorporation assays and annexin V/PI assays respectively. Total p21 protein levels were compared using flow cytometry and western blotting. p21 mRNA was assessed by RT-PCR. Intracellular p21 staining was performed to assess cellular distribution of total protein. To further confirm observations siRNA was used to knockdown MIF protein inwtcells. Cell cycle analysis was performed using PI incorporation assays.ResultsMIF-/- murine dermal fibroblasts exhibited reduced proliferative responses and were more susceptible to apoptosis. This was associated with reduced p21 expression and nuclear distribution. Treatment with recombinant MIF protein was demonstrated to reduce both basal and induced apoptosis and increase nuclear p21 expression. Reduced nuclear p21 expression was also observed in MIF siRNA treatedwtcells.ConclusionThe results demonstrate that in the absence of MIF p21 expression and nuclear distribution is reduced which is associated with a reduction in cell growth and increased apoptosis. MIF may therefore play a role in maintaining homeostatic control of p21.
Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes
Authors: Merkley Mark A , Hildebrandt Ellen , Podolsky Robert H , Arnouk Hilal , Ferris Daron G , Dynan William S , Stöppler Hubert 
Published: August 2009

Abstract

Background
Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features.

Results
Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27).

Conclusion
This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.
HIV and hepatitis C virus infections among hanka injection drug users in central Ukraine: a cross-sectional survey
Authors: Dumchev Kostyantyn V , Soldyshev Ruslan , Qian Han-Zhu , Zezyulin Olexandr O , Chandler Susan D , Slobodyanyuk Pavel , Moroz Larisa , Schumacher Joseph E 
Published: August 2009

Abstract

Background
Ukraine has experienced an increase in injection drug use since the 1990s. An increase in HIV and hepatitis C virus infections has followed, but not measures of prevalence and risk factors. The purposes of this study are to estimate the prevalence of HIV, HCV, and co-infection among injection drug users (IDUs) in central Ukraine and to describe risk factors for HIV and HCV.

Methods
A sample of 315 IDUs was recruited using snowball sampling for a structured risk interview and HIV/HCV testing (81.9% male, 42% single, average age 28.9 years [range = 18 to 55]).

Results
HIV and HCV antibodies were detected in 14.0% and 73.0%, respectively, and 12.1% were seropositive for both infections. The most commonly used drug was hanka, home-made from poppy straw and often mixed with other substances including dimedrol, diazepines, and hypnotics. The average period of injecting was 8.5 years; 62.5% reported past-year sharing needles or injection equipment, and 8.0% shared with a known HIV-positive person. More than half (51.1%) reported multiple sexual partners, 12.9% buying or selling sex, and 10.5% exchanging sex and drugs in the past year. Those who shared with HIV positive partners were 3.4 times more likely to be HIV positive than those who did not. Those who front- or back-loaded were 4 times more likely to be HCV positive than those who did not.

Conclusion
Harm reduction, addiction treatment and HIV prevention programs should address risk factors to stop further spread of both HIV and HCV among IDUs and to the general population in central Ukraine.
Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia
Authors: Lavee Michal , Goldman Shlomit , Daniel-Spiegel Etty , Shalev Eliezer 
Published: August 2009

Abstract

Objective
To evaluate levels of matrix metalloproteinases (MMP) and their inhibitors (TIMP) in second trimester amniotic fluid of women with hypertensive disorders compared to normotensive women.

Study Design
Amniotic fluid was obtained from 133 women undergoing genetic second trimester amniocentesis. Zymography was performed for MMP characterization and an MMP-2 ELISA kit was used to determine MMP-2 levels. TIMP-2 expression was evaluated using western blot.

Results
Mean amniotic fluid MMP-2 and TIMP-2 levels were significantly higher in women who developed a hypertensive disorder compared to normotensive women (P < 0.0004 and P < 0.01, respectively). When subdivided into subgroups, amniotic fluid from women who eventually developed preeclampsia or superimposed preeclampsia showed significantly higher MMP-2 levels than normotensive women (P < 0.05). However, no statistical difference in MMP-2 levels was found between patients with gestational hypertension and normotensive patients.

Conclusion
Higher amniotic fluid MMP-2 and TIMP-2 levels are found in women who eventually develop preeclampsia.