bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased NO bioavailability in aging male rats by genistein and exercise training: using 4, 5-diaminofluorescein diacetate
Authors: Eksakulkla Sukanya , Suksom Daroonwan , Siriviriyakul Prasong , Patumraj Suthiluk 
Published: September 2009

Abstract

Background
Several kinds of anti-oxidants have drawn a lot of intension for their benefits on vascular protection. In addition, it has been demonstrated that exercise training could improve endothelial function by up-regulating endothelial nitric oxide synthase (eNOS) protein. Therefore, the present study aims to investigate the effects of genistein, a potent phyto-antioxidant, and exercise training on age-induced endothelial dysfunction in relation to NO bioavailability using in situ NO-sensitive fluorescent dye detection.

Methods
Male Wistar rats (20-22-month old) were divided into four groups: aged rats treated with corn oil, (Aged+Veh, n = 5), aged rats treated with genistein (Aged+Gen, n = 5, (0.25 mg/kg BW/day, s.c.)), aged rats with and without exercise training (Aged+Ex, n = 5, swimming 40 min/day, 5 days/week for 8 weeks) (Aged+Without-Ex, n = 5). Cremaster arterioles (15-35 micrometer) were visualized by fluorescein isothiocyanate labeled dextran (5 microgram/ml). The vascular response to acetylcholine (Ach; 10-5M, 5 ml/5 min) was accessed after 1-min norepinephrine preconstriction (10 micro molar). To determine NO bioavailability, the Krebs-Ringer buffer with 4, 5-diaminofluorescein-diacetate (3 micro molar DAF-2DA), and 10 micro- molar Ach saturated with 95%N2 and 5%CO2 were used. Changes of DAF-2T-intensities along the cremaster arterioles were analyzed by the Image Pro-Plus Software (Media Cybernatics, Inc, USA). Liver malondialdehyde (MDA) level was measured by thiobarbituric acid reaction and used as an indicator for oxidative stress.

Results
The results showed that means arterial blood pressure for both Aged+Gen and Aged+Ex groups were significantly reduced when compared to the Aged groups, Aged+Veh and Aged+Without-Ex (P < 0.05). Among the treated groups, Ach-induced vasodilatation were significantly increased (P < 0.05) and was associated with increased NO-associated fluorescent intensities (P < 0.05). On the other hand, MDA levels were significantly reduced (P < 0.05) when Aged+Veh was compared to Aged+Without-Ex.

Conclusion
These findings showed that genistein and exercise training could improve age-induced endothelial dysfunction and is related to the increased NO bioavailability.
A cross-study gene set enrichment analysis identifies critical pathways in endometriosis
Authors: Zhao Hongbo , Wang Qishan , Bai Chunyan , He Kan , Pan Yuchun 
Published: September 2009

Abstract

Background
Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis.

Methods
We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets.

Results
We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues.

Conclusion
The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.
Receptor oligomerization and beyond: a case study in bone morphogenetic proteins
Authors: Heinecke Kai , Seher Axel , Schmitz Werner , Mueller Thomas D , Sebald Walter , Nickel Joachim 
Published: September 2009

Abstract

Background

Transforming growth factor (TGF)β superfamily members transduce signals by oligomerizing two classes of serine/threonine kinase receptors, termed type I and type II. In contrast to the large number of ligands only seven type I and five type II receptors have been identified in mammals, implicating a prominent promiscuity in ligand-receptor interaction. Since a given ligand can usually interact with more than one receptor of either subtype, differences in binding affinities and specificities are likely important for the generation of distinct ligand-receptor complexes with different signaling properties.

Results

In vitro interaction analyses showed two different prototypes of binding kinetics, 'slow on/slow off' and 'fast on/fast off'. Surprisingly, the binding specificity of ligands to the receptors of one subtype is only moderate. As suggested from the dimeric nature of the ligands, binding to immobilized receptors shows avidity due to cooperative binding caused by bivalent ligand-receptor interactions. To compare these in vitro observations to the situation in vivo, binding studies on whole cells employing homodimeric as well as heterodimeric bone morphogenetic protein 2 (BMP2) mutants were performed. Interestingly, low and high affinity binding sites were identified, as defined by the presence of either one or two BMP receptor (BMPR)-IA receptor chains, respectively. Both sites contribute to different cellular responses in that the high affinity sites allow a rapid transient response at low ligand concentrations whereas the low affinity sites facilitate sustained signaling but higher ligand concentrations are required.

Conclusion

Binding of a ligand to a single high affinity receptor chain functioning as anchoring molecule and providing sufficient complex stability allows the subsequent formation of signaling competent complexes. Another receptor of the same subtype, and up to two receptors of the other subtype, can then be recruited. Thus, the resulting receptor arrangement can principally consist of four different receptors, which is consistent with our interaction analysis showing low ligand-receptor specificity within one subtype class. For BMP2, further complexity is added by the fact that heterooligomeric signaling complexes containing only one type I receptor chain can also be found. This indicates that despite prominent ligand receptor promiscuity a manifold of diverse signals might be generated in this receptor limited system.
Pathophysiology of age-related diseases
Authors: Campisi Giuseppina , Chiappelli Martina , De Martinis Massimo , Franco Vito , Ginaldi Lia , Guiglia Rosario , Licastro Federico , Lio Domenico 
Published: September 2009

Abstract
A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention.
Torque Teno Virus (TTV) distribution in healthy Russian population
Authors: Vasilyev Evgeny V , Trofimov Dmitry Y , Tonevitsky Alexander G , Ilinsky Valery V , Korostin Dmitriy O , Rebrikov Denis V 
Published: September 2009

Abstract

Background
Torque teno virus (TTV) is a circular, single-stranded DNA virus that chronically infects healthy individuals of all ages worldwide. There is a lot of data on the prevalence and genetic heterogeneity of TTV in healthy populations and in patients with various diseases now available. However, little is known about TTV load among healthy human population. In this study we analyzed TTV load in the group of 512 Russian elite athletes, who are supposed to be, by some standards, the healthiest part of the human population.

Results
The prevalence rate of TTV among the Russian Olympic Reserve members was 94% (for test sensitivity about 1000 genome equivalents per 1 ml of blood). Quantities varied from 103 (which corresponded to detection limit) to 1010 copies per 1 ml of blood, with median at 2.7 × 106 copies.

Conclusion
About 94% of healthy individuals in Russian population have more than 1000 TTV genome copies per 1 ml of blood. This result exceeds the previously published data, and can be explained by either more sensitive PCR test system or by higher TTV distribution in Russian population or both. TTV viral load neither depends on gender, nor age.
Cysteine protease activation and apoptosis in Murine norovirus infection
Authors: Furman Linnzi M , Maaty Walid S , Petersen Lena K , Ettayebi Khalil , Hardy Michele E , Bothner Brian 
Published: September 2009

AbstractBackgroundNoroviruses are the leading cause of viral gastroenteritis. Because a suitablein vitroculture system for the human virus has yet to be developed, many basic details of the infection process are unknown. Murine norovirus (MNV) serves as a model system for the study of norovirus infection. Recently it was shown that infection of RAW 264.7 cells involved a novel apoptotic pathway involving survivin.ResultsUsing a different set of approaches, the up-regulation of caspases, DNA condensation/fragmentation, and membrane blebbing, all of which are markers of apoptosis, were confirmed. Live cell imaging and activity-based protein profiling showed that activation of caspase-like proteases occurred within two hours of infection, followed by morphological changes to the cells. MNV infection in the presence of caspase inhibitors proceeded via a distinct pathway of rapid cellular necrosis and reduced viral production. Affinity purification of activity-based protein profiling targets and identification by peptide mass fingerprinting showed that the cysteine protease cathepsin B was activated early in infection, establishing this protein as an upstream activator of the intrinsic apoptotic pathway.ConclusionThis work adds cathepsin B to the noncanonical programmed cell death induced by MNV, and provides data suggesting that the virus may induce apoptosis to expand the window of time for viral replication. This work also highlights the significant power of activity-based protein profiling in the study of viral pathogenesis.
Hybrid stochastic simplifications for multiscale gene networks
Authors: Crudu Alina , Debussche Arnaud , Radulescu Ovidiu 
Published: September 2009

AbstractBackgroundStochastic simulation of gene networks by Markov processes has important applications in molecular biology. The complexity of exact simulation algorithms scales with the number of discrete jumps to be performed. Approximate schemes reduce the computational time by reducing the number of simulated discrete events. Also, answering important questions about the relation between network topology and intrinsic noise generation and propagation should be based on general mathematical results. These general results are difficult to obtain for exact models.ResultsWe propose a unified framework for hybrid simplifications of Markov models of multiscale stochastic gene networks dynamics. We discuss several possible hybrid simplifications, and provide algorithms to obtain them from pure jump processes. In hybrid simplifications, some components are discrete and evolve by jumps, while other components are continuous. Hybrid simplifications are obtained by partial Kramers-Moyal expansion [1–3] which is equivalent to the application of the central limit theorem to a sub-model. By averaging and variable aggregation we drastically reduce simulation time and eliminate non-critical reactions. Hybrid and averaged simplifications can be used for more effective simulation algorithms and for obtaining general design principles relating noise to topology and time scales. The simplified models reproduce with good accuracy the stochastic properties of the gene networks, including waiting times in intermittence phenomena, fluctuation amplitudes and stationary distributions. The methods are illustrated on several gene network examples.ConclusionHybrid simplifications can be used for onion-like (multi-layered) approaches to multi-scale biochemical systems, in which various descriptions are used at various scales. Sets of discrete and continuous variables are treated with different methods and are coupled together in a physically justified approach.
As the bell tolls: a foundation study on pancreatic cancer consumer's research priorities
Authors: Saunders Carla , Gooden Helen , Robotin Monica , Mumford Jan 
Published: September 2009

Abstract

Background
This is the first investigation of its kind to explore the views of people affected by pancreatic cancer with regard to research priorities. Pancreatic cancer has an extremely poor outlook in terms of early diagnosis, effective treatment and survival. Those affected by the disease generally lack opportunities to voice their needs or concerns in an organised manner, link with others affected by the condition and take part in research.

Methods
This qualitative study adopts a self-selected telephone focussed discussion group approach. Information was obtained from distinct carer and patient groups after adequate controls such as the 'safe space' technique (repeatedly enquiring on and respecting the emotional needs) were implemented to protect participants from undue physical and psychological distress.

Results
Five themes emerged overall, with three themes being common between the patients and carers groups. Early detection, clinician communication and public awareness were areas of recurring discussion and consensus for both groups. The fourth theme to emerge for the patient group centred on quality of care, while the fourth theme of the carer group focused on the need for more and improved treatment options.

Conclusion
Research priorities for pancreatic cancer consumers have been identified via an investigation that was tailored to meet exceptional needs. This research gives us a primary understanding of the role that pancreatic cancer patients can play in identifying areas of research that are responsive to their needs and priorities when suitably planned. Importantly it also provides a much greater understanding of the grim realities of the disease for those affected. This work is likely to be of value to anyone planning to work with those with a time limited, challenging condition.
Nonopportunistic Neurologic Manifestations of the Human Immunodeficiency Virus: An Indian Study
Authors: Deshpande Alaka K , Patnaik Mrinal M 
Published: September 2009

ContextHIV‐1 is a neurotropic virus. In a resource‐limited country such as India, large populations of affected patients now have access to adequate chemoprophylaxis for opportunistic infections (OIs), allowing them to live longer. Unfortunately the poor availability of highly active antiretroviral therapy (HAART) has allowed viral replication to proceed unchecked. This has resulted in an increase in the debilitating neurologic manifestations directly mediated by the virus.ObjectiveThe main objective of this study was to identify and describe in detail the direct neurologic manifestations of HIV‐1 in antiretroviral treatment (ART)‐naive, HIV‐infected patients (excluding the neurologic manifestations produced by opportunistic pathogens).DesignThree hundred successive cases of HIV‐1 infected, ART‐naive patients with neurologic manifestations were studied over a 3‐year period. Each case was studied in detail to identify and then exclude manifestations due to opportunistic pathogens. The remaining cases were then analyzed specially in regard to their occurrence and the degree of immune suppression (CD4+ cell counts).Setting and PatientsThe study was carried out in an apex, tertiary, referral care center for HIV/AIDS in India. All patients were admitted for a detailed analysis.No interventions were carried out, as this was an observational study.ResultsOf the 300 cases, 67 (22.3%) had neurologic manifestations due to the direct effects of HIV‐1. The HIV infection involved the neuroaxis at all levels. The distribution of cases showed that the region most commonly involved was the brain (50.7%). The manifestations included stroke syndromes (29.8%), demyelinating illnesses (5.9%), AIDS dementia complex (5.9%), and venous sinus thrombosis (4.4%). The other manifestations seen were peripheral neuropathies (35.8% of cases), spinal cord pathologies (5.9% of cases), radiculopathies (4.4% of cases), and a single case of myopathy. The onset of occurrence of these diseases and their progression were then correlated with the CD4+ cell counts.ConclusionHIV infection is responsible for a large number of nonopportunistic neurologic manifestations that occur across a large immune spectrum. During the early course of the disease, the polyclonal hypergammaglobulinemia induced by the virus results in demyelinating diseases of the central‐ and peripheral nervous systems (CNS and PNS). As the HIV infection progresses, the direct toxic effects of the virus unfold, directly damaging the CNS and PNS, resulting in protean clinical manifestations.
Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4+ T lymphocytes
Authors: Ramakrishnan Rajesh , Dow Eugene C , Rice Andrew P 
Published: September 2009

Abstract
Low levels of Cdk9 T-loop autophosphorylation in quiescent CD4+ T lymphocytes may limit RNA polymerase II elongation.
The cellular kinase complex P-TEFb is composed of Cdk9 and cyclin T, and it is required for expression of most protein-coding genes by RNAP II. Cdk9 has been shown recently to be activated in cis by autophosphorylation of Thr186 in its T-loop. Using a phosphospecific Cdk9 antibody, we examined the level of Cdk9 T-loop phosphorylation in resting and activated CD4+ T lymphocytes. Cdk9 T-loop phosphorylation was found to be low-to-undetectable in resting CD4+ T lymphocytes, and upon activation by distinct stimuli, there is a rapid (&lt;1 h) increase in pCdk9 that does not require protein synthesis. The low level of Cdk9 T-loop phosphorylation was not to be a result of the absence of an associated regulatory cyclin partner. These observations suggest that autophosphorylation of the Cdk9 T-loop is repressed in resting CD4+ T lymphocytes. The low level of T-loop phosphorylation in resting cells is also reflected in a low level of phosphorylation of Ser2 in the carboxyl terminal domain of RNAP II, suggesting that lack of Cdk9 T-loop autophosphorylation may limit RNAP II elongation in quiescent CD4+ T lymphocytes.
Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP
Authors: Rørvig Sara , Honore Christian , Larsson Lars-Inge , Ohlsson Sophie , Pedersen Corinna C , Jacobsen Lars C , Cowland Jack B , Garred Peter , Borregaard Niels 
Published: September 2009

Abstract
Ficolin-1 is present in gelatinase granules and also in a previously unknown highly mobilizable subset of granules; once released, ficolin-1 binds to the neutrophil surface.
Ficolins are soluble molecules that bind carbohydrate present on the surface of microorganisms and function as recognition molecules in the lectin complement pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and ficolin-3. Ficolin-1 is synthesized in monocytes and type II alveolar epithelial cells. Ficolin-1 has been shown to be present in secretory granules of human neutrophils, but it is not known which subset of the neutrophils’ secretory granules harbors ficolin-1. To determine the exact subcellular localization of ficolin-1 in neutrophils, recombinant ficolin-1 was expressed in Chinese hamster ovary cells and used for generation of polyclonal antibodies. This allowed detection of ficolin-1 in subcellular fractions of human neutrophils by ELISA, by Western blotting, and by immunohistochemistry. Real-time PCR examination of normal human bone marrow showed FCN1 gene expression largely in myelocytes, metamyelocytes, and band cells with a profile quite similar to that of gelatinase. In accordance with this, biosynthesis studies of neutrophils precursor cells showed that ficolin-1 was primarily synthesized in myelocytes, metamyelocytes, and band cells. Immunohistochemistry and subcellular fractionation demonstrated that ficolin-1 is primarily localized in gelatinase granules but also in highly exocytosable gelatinase-poor granules, not described previously. Ficolin-1 is released from neutrophil granules by stimulation with fMLP or PMA, and the majority becomes associated with the surface membrane of the cells and can be detected by flow cytometry. Our studies show that neutrophils are a major source of ficolin-1, which can be readily exocytosed by stimulation.
Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers
Authors: Joshi Shilpa , Lewis Stephen J , Creanor Siobhan , Ayling Ruth M 
Published: September 2009

Objective Measurement of the faecal markers calprotectin, lactoferrin and tumour M2-PK has been reported to be useful in the diagnosis and management of a range of gastrointestinal disorders in both children and adults. The aim of this study was to investigate the requirement for age-related reference ranges. Methods Faecal samples were obtained from 132 healthy subjects and analysis of calprotectin, lactoferrin and tumour M2-PK performed using commercially available enzyme-linked immunosorbent assay. Results In the healthy subjects median concentrations were as follows: for calprotectin – 2–9 y, 34 μg/g, 10–59 y, 22 μg/g and ≥60 y, 27 μg/g; for lactoferrin – 2–9 y, 2.2 μg/g, ≥10 y, 0.5 μg/g; and for tumour M2-PK all subjects <1 U/mL. Significant differences between age groups for different markers resulted in the following age-related reference ranges: calprotectin – 2–9 y, <166 μg/g, 10–59 y, <51 μg/g, ≥60 y, <112 μg/g; lactoferrin – 2–9 y, <29 μg/g, ≥10 y <4.6 μg/g. Conclusion In healthy individuals, we found there to be variation in the faecal inflammatory markers calprotectin and lactoferrin with age. For both calprotectin and lactoferrin children aged 2–9 y had significantly higher concentrations than subjects aged ≥10 y. For calprotectin but not lactoferrin, adults ≥60 years had a higher concentration than those aged 10–59 y. There was no change with age in the metabolomic marker faecal tumour M2-PK in healthy subjects. The knowledge of age-related reference ranges in healthy subjects is important to fully interpret changes in gastrointestinal disease.