bluuebunny/crossref_metadata_2025_split huggingface dataset:
A major role of TGF-β1 in the homing capacities of murine hematopoietic stem cell/progenitors
Authors: Capron Claude , Lacout Catherine , Lécluse Yann , Jalbert Valérie , Chagraoui Hédia , Charrier Sabine , Galy Anne , Bennaceur-Griscelli Annelise , Cramer-Bordé Elisabeth , Vainchenker William 
Published: May 2010

AbstractTransforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine with major in vitro effects on hematopoietic stem cells (HSCs) and lymphocyte development. Little is known about hematopoiesis from mice with constitutive TGF-β1 inactivation largely because of important embryonic lethality and development of a lethal inflammatory disorder in TGF-β1−/− pups, making these studies difficult. Here, we show that no sign of the inflammatory disorder was detectable in 8- to 10-day-old TGF-β1−/− neonates as judged by both the number of T-activated and T-regulator cells in secondary lymphoid organs and the level of inflammatory cytokines in sera. After T-cell depletion, the inflammatory disease was not transplantable in recipient mice. Bone marrow cells from 8- to 10-day-old TGF-β1−/− neonates showed strikingly impaired short- and long-term reconstitutive activity associated with a parallel decreased in vivo homing capacity of lineage negative (Lin−) cells. In addition an in vitro–reduced survival of immature progenitors (Lin− Kit+ Sca+) was observed. Similar defects were found in liver cells from TGF-β1−/− embryos on day 14 after vaginal plug. These data indicate that TGF-β1 is a critical regulator for in vivo homeostasis of the HSCs, especially for their homing potential.
Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation
Authors: Lindner Ines , Meier Christiane , Url Angelika , Unger Hermann , Grassauer Andreas , Prieschl-Grassauer Eva , Doerfler Petra 
Published: May 2010

Abstract

Background
Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects.

Results
In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone.

Conclusions
We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases.
Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features
Authors: Ang Pei Woon , Loh Marie , Liem Natalia , Lim Pei Li , Grieu Fabienne , Vaithilingam Aparna , Platell Cameron , Yong Wei Peng , Iacopetta Barry , Soong Richie 
Published: May 2010

Abstract

Background
Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups.

Methods
DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS.

Results
A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001).

Conclusions
Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.
Lutein-fortified infant formula fed to healthy term infants: evaluation of growth effects and safety
Authors: Capeding Rosario , Gepanayao Connie P , Calimon Nerrisa , Lebumfacil Jowena , Davis Anne M , Stouffer Nicole , Harris Bruce J 
Published: May 2010

Abstract

Background/Objectives
Breast milk contains lutein derived from the mother's diet. This carotenoid is currently not added to infant formula, which has a small and variable lutein content from innate ingredients. This study was conducted to compare the growth of infants fed lutein-fortified infant formula with that of infants fed infant formula without lutein fortification.

Subjects/Methods
This 16-week study was prospective, randomized, controlled, and double-blind with parallel groups of healthy term infants fed either control formula (Wyeth S-26 Gold, designated as Gold) or experimental formula (Wyeth S-26 Gold fortified with lutein at 200 mcg/l, designated as Gold + Lutein). Two hundred thirty-two (232) infants ≤ 14 days postnatal age were randomized and 220 (94.8%) completed the study. Weight (g), head circumference (cm), and length (cm) were measured at Weeks 4, 8, 12, and 16. The primary endpoint was weight gain (g/day) from baseline to Week 16. Safety was assessed through monitoring of study events (SEs) throughout the study and evaluation of selected blood chemistry tests performed at Week 16.

Results
Infants in both treatment groups demonstrated appropriate growth. No differences between treatment groups were found in any of the measures of growth at any of the measurement time points. Both study formulas were well tolerated. The mean values of all measured blood chemistry parameters fell within the modified normal ranges for infants, and the values for both groups for any measured parameter were similar.

Conclusions
Infants fed lutein-fortified S-26 Gold demonstrated growth equivalent to that of infants fed unfortified lutein formula.
Built and socioeconomic environments: patterning and associations with physical activity in U.S. adolescents
Authors: Boone-Heinonen Janne , Evenson Kelly R , Song Yan , Gordon-Larsen Penny 
Published: May 2010

Abstract

Background
Inter-relationships among built and socioeconomic environmental characteristics may result in confounding of associations between environment exposure measures and health behaviors or outcomes, but traditional multivariate adjustment can be inappropriate due to collinearity.

Methods
We used principal factor analysis to describe inter-relationships between a large set of Geographic Information System-derived built and socioeconomic environment measures for adolescents in the National Longitudinal Study of Adolescent Health (Wave I, 1995-96, n = 17,294). Using resulting factors in sex-stratified multivariate negative binomial regression models, we tested for confounding of associations between built and socioeconomic environment characteristics and moderate to vigorous physical activity (MVPA). Finally, we used knowledge gained from factor analysis to construct replicable environmental measures that account for inter-relationships and avoid collinearity.

Results
Using factor analysis, we identified three built environment constructs [(1) homogenous landscape; 2) development intensity with high pay facility count; 3) development intensity with high public facility count] and two socioeconomic environment constructs [1) advantageous economic environment, 2) disadvantageous social environment]. In regression analysis, confounding of built environment-MVPA associations by socioeconomic environment factors was stronger than among built environment factors. In fully adjusted models, MVPA was negatively associated with the highest (versus lowest) quartile of homogenous land cover in males [exp(coeff) (95% CI): 0.91 (0.86, 0.96)] and intensity (pay facilities) [exp(coeff) (95% CI): 0.92 (0.85, 0.99)] in females. Single proxy measures (Simpson's diversity index, count of pay facilities, count of public facilities, median household income, and crime rate) representing each environmental construct replicated associations with MVPA.

Conclusions
Environmental characteristics are inter-related. Both built and SES environments should be incorporated into analysis in order to minimize confounding. Single environmental measures may be useful proxies for environmental constructs in longitudinal analysis and replication in external populations, but more research is needed to better understand mechanisms of action, and ultimately identify policy-relevant environmental determinants of physical activity.
Effects of unilateral robotic limb loading on gait characteristics in subjects with chronic stroke
Authors: Khanna Ira , Roy Anindo , Rodgers Mary M , Krebs Hermano I , Macko Richard M , Forrester Larry W 
Published: May 2010

Abstract

Background
Hemiparesis after stroke often leads to impaired ankle motor control that impacts gait function. In recent studies, robotic devices have been developed to address this impairment. While capable of imparting forces to assist during training and gait, these devices add mass to the paretic leg which might encumber patients' gait pattern. The purpose of this study was to assess the effects of the added mass of one of these robots, the MIT's Anklebot, while unpowered, on gait of chronic stroke survivors during overground and treadmill walking.

Methods
Nine chronic stroke survivors walked overground and on a treadmill with and without the anklebot mounted on the paretic leg. Gait parameters, interlimb symmetry, and joint kinematics were collected for the four conditions. Repeated-measures analysis of variance (ANOVA) tests were conducted to examine for possible differences across four conditions for the paretic and nonparetic leg.

Results
The added inertia and friction of the unpowered anklebot had no statistically significant effect on spatio-temporal parameters of gait, including paretic and nonparetic step time and stance percentage, in both overground and treadmill conditions. Noteworthy, interlimb symmetry as characterized by relative stance duration was greater on the treadmill than overground regardless of loading conditions. The presence of the unpowered robot loading reduced the nonparetic knee peak flexion on the treadmill and paretic peak dorsiflexion overground (p < 0.05).

Conclusions
Our results suggest that for these subjects the added inertia and friction of this backdriveable robot did not significantly alter their gait pattern.
5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication
Authors: Ranjan Priya , Jayashankar Lakshmi , Deyde Varough , Zeng Hui , Davis William G , Pearce Melissa B , Bowzard John B , Hoelscher Mary A , Jeisy-Scott Victoria , Wiens Mayim E , Gangappa Shivaprakash , Gubareva Larisa , García-Sastre Adolfo , Katz Jacqueline M , Tumpey Terrence M , Fujita Takashi , Sambhara Suryaprakash 
Published: May 2010

Abstract

Background
Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state.

Results
In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5'PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice.

Conclusions
Our findings suggest that 5'PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.
Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses
Authors: Ngaosuwankul Nathamon , Noisumdaeng Pirom , Komolsiri Pisut , Pooruk Phisanu , Chokephaibulkit Kulkanya , Chotpitayasunondh Tawee , Sangsajja Chariya , Chuchottaworn Charoen , Farrar Jeremy , Puthavathana Pilaipan 
Published: May 2010

Abstract

Background
Nasopharyngeal aspirate (NPA), nasal swab (NS), and throat swab (TS) are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number.

Results
Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus), NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed.

Conclusion
Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS.
Human herpesvirus 6 infection impairs Toll-like receptor signaling
Authors: Murakami Yuichi , Tanimoto Kazushi , Fujiwara Hiroshi , An Jun , Suemori Koichiro , Ochi Toshiki , Hasegawa Hitoshi , Yasukawa Masaki 
Published: May 2010

AbstractHuman herpesvirus 6 (HHV-6) has a tropism for immunocompetent cells, including T lymphocytes, monocytes/macrophages, and dendritic cells (DCs) suggesting that HHV-6 infection affects the immunosurveillance system. Toll-like receptor (TLR) system plays an important role in innate immunity against various pathogens. In the present study, we investigated the effect of HHV-6 infection on the expression and intracellular signaling of TLRs in DCs. Although expression levels of TLRs were not decreased or slightly elevated following HHV-6 infection, the amounts of cytokines produced following stimulation with ligands for TLRs appeared to be dramatically decreased in HHV-6-infected DCs as compared to mock-infected DCs. Similarly, phosphorylation levels of TAK-1, IκB kinase, and IκB-α following stimulation of HHV-6-infected DCs with lipopolysaccharide, which is the ligand for TLR4, appeared to be decreased. These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation.
NF-κB dependent and independent mechanisms of quartz-induced proinflammatory activation of lung epithelial cells
Authors: van Berlo Damien , Knaapen Ad M , van Schooten Frederik-Jan , Schins Roel PF , Albrecht Catrin 
Published: May 2010

Abstract
In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-κB pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-IκBα in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE) cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-κB independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-κB signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNFα and IL-1β in macrophage supernatant did not reduce its ability to elicit NF-κB activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione.
The results from the current work suggest that although both oxidative stress and NF-κB are likely involved in the inflammatory effects of toxic respirable particles, these phenomena can operate independently on the cellular level. This might have consequences for in vitro particle hazard testing, since by focusing on NF-κB signalling one might neglect alternative inflammatory pathways.
The distribution of four trace elements (Fe, Mn, Cu, Zn) in forage and the relation to scrapie in Iceland
Authors: Eiríksson Tryggvi , Björnsson Hólmgeir , Gudmundsdóttir Kristín Björg , Kristinsson Jakob , Jóhannesson Torkell 
Published: May 2010

Abstract

Background
Previous studies indicated that the iron (Fe)/manganese (Mn) ratio in forage of sheep was significantly higher on scrapie-afflicted farms than on farms in other scrapie categories. This study was conducted to examine whether Fe and Mn in forage of sheep varied in general according to the scrapie status of different areas in the country. Copper (Cu) and zinc (Zn) were also included because of a possible relation to scrapie.

Methods
The country was subdivided into seven Areas (I-VII). Three Areas (I, IV, VII) were designated scrapie-free (never diagnosed or eradicated) and three as scrapie-endemic (II, III, VI); status of Area V was taken as unsettled. Of the harvest 2007 1552 samples were analysed from 344 farms all over the country, mostly grass silage from plastic bales (>90%) and from the first cut (70% or more). Results were expressed as mg kg-1 dry matter.

Results
Fe varied enormously from less than 100 mg kg-1 to 5000 mg kg-1. Mn varied nearly thirtyfold (17-470 mg kg-1). Fe concentration was significantly lower in Area I than in Areas II, V and VI. Mn concentration was significantly higher in Areas I, IV and VII than in Areas II, III, V and VI. The Fe/Mn ratio was significantly less in Area I than in the other areas (except Area IV). Mean Cu concentration was 6.6-8.3 mg kg-1 and the mean Zn concentration was 24-29 mg kg-1. They differed significantly in some areas.

Conclusions
1) Fe tended to be in lower amounts in sheep forage in scrapie-free than in endemic areas; 2) Mn was in higher amounts in forage in scrapie-free than endemic areas; 3) the Fe/Mn ratio was lower in scrapie-free than in endemic areas; 4) the Fe/Mn ratio may possibly be used as an indicator of scrapie status; 5) Cu and Zn in sheep forage were not related to scrapie; 6) further study on the role of Fe and Mn in the occurrence of scrapie in Iceland is needed.
Functional tissue engineering of ligament healing
Authors: Hsu Shan-Ling , Liang Rui , Woo Savio LY 
Published: May 2010

AbstractLigaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally.