bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10
Authors: Alfaro-Moreno E. , Nawrot T. S. , Vanaudenaerde B. M. , Hoylaerts M. F. , Vanoirbeek J. A. , Nemery B. , Hoet P. H. M. 
Published: July 2008

The current authors evaluated whether a system of co-cultures of relevant cells (pneumocytes (A549), macrophages (THP-1), mast cells (HMC-1) and endothelial cells (EAHY926)) would mimic the responses to particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10) previously reportedin vivo. The role of mast cells was considered of special interest.Single cultures, bicultures (A549 + HMC-1 in a 10:1 ratio; THP-1 + HMC-1 in a 2:1 ratio) and tricultures (A549 + THP-1 + HMC-1 in a 10:2:1 ratio) were exposed to urban PM10(24 h at 0, 10, 30 or 100 µg·cm−2). Additionally, EAHY926 cells were introduced in inserts above the tricultures. The released cytokines were evaluated with a fluorescence-activated cell sorter array system.THP-1 + HMC-1 bicultures and the tricultures released more granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein (MIP)-1β, interleukin (IL)-1β, IL-8, IL-6, tumour necrosis factor-α and MIP-1α in response to PM10than the sum of the single cultures. Tricultures with EAHY926 released more G-CSF, MIP-1α, IL-8 and MIP-1β than the EAHY926 single culture.The bicultures, tricultures and tricultures with EAHY926 provide results that are consistent with the local and systemic effects previously described for particulate matter effects,i.e.inflammation, endothelial dysfunction and bone marrow cell mobilisation. Mast cells seem to play a significant role in the co-culture responses.
The effect of OSAS on sick leave and work disability
Authors: Sivertsen B. , Øverland S. , Glozier N. , Bjorvatn B. , Mæland J. G. , Mykletun A. 
Published: July 2008

The objective of the present study was to examine the independent contribution of symptoms of obstructive sleep apnoea syndrome (OSAS) to long-term sick leave and permanent work disability.Using a historical cohort design with 4 yrs of follow-up, information on sick leave and disability benefit recipiency were merged with health information from the Hordaland Health Study, carried out in western Norway during 1997–1999. Persons aged 40–45 yrs (n = 7,028) were assessed for self-reported symptoms of OSAS (snoring, breathing cessations and daytime sleepiness), body mass index, somatic conditions and other potential confounders. The outcomes, cumulative sick leave of ≥8 weeks and permanent work disability, were identified in records from the National Insurance Administration.After excluding participants with work disability at baseline, symptoms of OSAS were found to be a significant predictor of both subsequent long-term sick leave and permanent work disability. These effects remained significant after adjustment for a range of possible confounding factors. Daytime sleepiness showed the greatest explanatory power, followed by breathing cessations and snoring.It is concluded that self-reported symptoms of obstructive sleep apnoea syndrome are an independent risk factor for subsequent long-term sick leave and permanent work disability. These findings need to be replicated using objective measures of obstructive sleep apnoea syndrome.
Interferon-β augments eosinophil adhesion-inducing activity of endothelial cells
Authors: Kobayashi T. , Takaku Y. , Yokote A. , Miyazawa H. , Soma T. , Hagiwara K. , Kanazawa M. , Nagata M. 
Published: July 2008

Viral infections induce exacerbations of asthma. One of the earliest host responses to viral infections is the production of innate cytokines including type I interferons (IFNs), such as IFN-β, which may act to modify airway inflammation. The objective of the present study was to investigate whether IFN-β modifies the eosinophil adhesion-inducing activity of endothelial cells.Human umbilical vein endothelial cells (HUVECs) were stimulated with IFN-β for 24 h in the presence or absence of tumour necrosis factor (TNF)-α. Eosinophils were isolated from the peripheral blood of healthy volunteers. The ability of the IFN-β-stimulated HUVEC monolayers to induce eosinophil adhesion was assessed according to the eosinophil peroxidase assay.Eosinophil adhesion to HUVECs was significantly augmented by IFN-β in the presence of TNF-α but not in its absence. The augmented adhesion was inhibited by anti-α4integrin monoclonal antibody (mAb) or anti-β2integrin mAb. IFN-β significantly enhanced the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 on HUVECs in the presence of TNF-α.Interferon-β can augment the adhesiveness of endothelial cells to eosinophils, mainly through the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. This action of interferon-β may contribute to the intensification of airway inflammation in asthma that is associated with exacerbations induced by viral infections.
Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy
Authors: de Laurentiis G. , Paris D. , Melck D. , Maniscalco M. , Marsico S. , Corso G. , Motta A. , Sofia M. 
Published: July 2008

Exhaled breath condensate (EBC) is a noninvasive method for the study of airway lining fluid. Nuclear magnetic resonance (NMR) spectroscopy can provide biochemical profiles of metabolites in biological samples. The aim of the present study was to validate the NMR metabonomic analysis of EBC in adults, assessing the role of pre-analytical variables (saliva and disinfectant contamination) and the potential clinical feasibility.In total, 36 paired EBC and saliva samples, obtained from healthy subjects, laryngectomised patients and chronic obstructive pulmonary disease patients, were analysed by means of1H-NMR spectroscopy followed by principal component analysis. The effect on EBC of disinfectant, used for reusable parts of the condenser, was assessed after different washing procedures. To evaluate intra-day repeatability, eight subjects were asked to collect EBC and saliva twice within the same day.All NMR saliva spectra were significantly different from corresponding EBC samples. EBC taken from condensers washed with recommended procedures invariably showed spectra perturbed by disinfectant. Each EBC sample clustered with corresponding samples of the same group, while presenting intergroup qualitative and quantitative signal differences (94% of the total variance within the data).In conclusion, the nuclear magnetic resonance metabonomic approach could identify the metabolic fingerprint of exhaled breath condensate in different clinical sets of data. Moreover, metabonomics of exhaled breath condensate in adults can discriminate potential perturbations induced by pre-analytical variables.
Effects of NGF, NT-3 and GDNF family members on neurite outgrowth and migration from pelvic ganglia from embryonic and newborn mice
Authors: Stewart Ashley L , Anderson Richard B , Kobayashi Kazuto , Young Heather M 
Published: July 2008

AbstractBackgroundPelvic ganglia are derived from the sacral neural crest and contain both sympathetic and parasympathetic neurons. Various members of the neurotrophin and GDNF families of neurotrophic factors have been shown to play important roles in the development of a variety of peripheral sympathetic and parasympathetic neurons; however, to date, the role of these factors in the development of pelvic ganglia has been limited to postnatal and older ages. We examined the effects of NGF, NT-3, GDNF, neurturin and artemin on cell migration and neurite outgrowth from explants of the pelvic ganglia from embryonic and newborn mice grown on collagen gels, and correlated the responses with the immunohistochemical localization of the relevant receptors in fixed tissue.ResultsCell migration assays showed that GDNF strongly stimulated migration of tyrosine hydroxylase (TH) cells of pelvic ganglia from E11.5, E14.5 and P0 mice. Other factors also promoted TH cell migration, although to a lesser extent and only at discrete developmental stages. The cells and neurites of the pelvic ganglia were responsive to each of the GDNF family ligands – GDNF, neurturin and artemin – from E11.5 onwards. In contrast, NGF and NT-3 did not elicit a significant neurite outgrowth effect until E14.5 onwards. Artemin and NGF promoted significant outgrowth of sympathetic (TH+) neurites only, whereas neurturin affected primarily parasympathetic (TH-negative) neurite outgrowth, and GDNF and NT-3 enhanced both sympathetic and parasympathetic neurite outgrowth. In comparison, collagen gel assays using gut explants from E11.5 and E14.5 mice showed neurite outgrowth only in response to GDNF at E11.5 and to neurturin only in E14.5 mice.ConclusionOur data show that there are both age-dependent and neuron type-dependent differences in the responsiveness of embryonic and neo-natal pelvic ganglion neurons to growth factors.
Spatial and temporal expression of the 23 murine Prolactin/Placental Lactogen-related genes is not associated with their position in the locus
Authors: Simmons David G , Rawn Saara , Davies Alastair , Hughes Martha , Cross James C 
Published: July 2008

Abstract

Background
The Prolactin (PRL) hormone gene family shows considerable variation among placental mammals. Whereas there is a single PRL gene in humans that is expressed by the pituitary, there are an additional 22 genes in mice including the placental lactogens (PL) and Prolactin-related proteins (PLPs) whose expression is limited to the placenta. To understand the regulation and potential functions of these genes, we conducted a detailed temporal and spatial expression study in the placenta between embryonic days 7.5 and E18.5 in three genetic strains.

Results
Of the 22 PRL/PL genes examined, only minor differences were observed among strains of mice. We found that not one family member has the same expression pattern as another when both temporal and spatial data were examined. There was also no correlation in expression between genes that were most closely related or between adjacent genes in the PRL/PL locus. Bioinformatic analysis of upstream regulatory regions identified conserved combinations (modules) of putative transcription factor binding sites shared by genes expressed in the same trophoblast subtype, supporting the notion that local regulatory elements, rather than locus control regions, specify subtype-specific expression. Further diversification in expression was also detected as splice variants for several genes.

Conclusion
In the present study, a detailed temporal and spatial placental expression map was generated for all murine PRL/PL family members from E7.5 to E18.5 of gestation in three genetic strains. This detailed analysis uncovered several new markers for some trophoblast cell types that will be useful for future analysis of placental structure in mutant mice with placental phenotypes. More importantly, several main conclusions about regulation of the locus are apparent. First, no two family members have the same expression pattern when both temporal and spatial data are examined. Second, most genes are expressed in multiple trophoblast cell subtypes though none were detected in the chorion, where trophoblast stem cells reside, or in syncytiotrophoblast of the labyrinth layer. Third, bioinformatic comparisons of upstream regulatory regions identified predicted transcription factor binding site modules that are shared by genes expressed in the same trophoblast subtype. Fourth, further diversification of gene products from the PRL/PL locus occurs through alternative splice isoforms for several genes.
Characterization of new IS elements and studies of their dispersion in two subspecies of Leifsonia xyli
Authors: Zerillo Marcelo M , Van Sluys Marie-Anne , Camargo Luis Eduardo A , Monteiro-Vitorello Claudia B 
Published: July 2008

Abstract

Background

Leifsonia xyli is a xylem-inhabiting bacterial species comprised of two subspecies: L. xyli subsp. xyli (Lxx) and L. xyli subsp. cynodontis (Lxc). Lxx is the causal agent of ratoon stunting disease in sugarcane commercial fields and Lxc colonizes the xylem of several grasses causing either mild or no symptoms of disease. The completely sequenced genome of Lxx provided insights into its biology and pathogenicity. Since IS elements are largely reported as an important source of bacterial genome diversification and nothing is known about their role in chromosome architecture of L. xyli, a comparative analysis of Lxc and Lxx elements was performed.

Results
Sample sequencing of Lxc genome and comparative analysis with Lxx complete DNA sequence revealed a variable number of IS transposable elements acting upon genomic diversity. A detailed characterization of Lxc IS elements and a comparative review with IS elements of Lxx are presented. Each genome showed a unique set of elements although related to same IS families when considering features such as similarity among transposases, inverted and direct repeats, and element size. Most of the Lxc and Lxx IS families assigned were reported to maintain transposition at low levels using translation regulatory mechanisms, consistent with our in silico analysis. Some of the IS elements were found associated with rearrangements and specific regions of each genome. Differences were also found in the effect of IS elements upon insertion, although none of the elements were preferentially associated with gene disruption. A survey of transposases among genomes of Actinobacteria showed no correlation between phylogenetic relatedness and distribution of IS families. By using Southern hybridization, we suggested that diversification of Lxc isolates is also mediated by insertion sequences in probably recent events.

Conclusion
Collectively our data indicate that transposable elements are involved in genome diversification of Lxc and Lxx. The IS elements were probably acquired after the divergence of the two subspecies and are associated with genome organization and gene contents. In addition to enhancing understanding of IS element dynamics in general, these data will contribute to our ongoing comparative analyses aimed at understanding the biological differences of the Lxc and Lxx.
Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity
Authors: Vicari Luisa , Musumeci Teresa , Giannone Ignazio , Adamo Luana , Conticello Concetta , De Maria Ruggero , Pignatello Rosario , Puglisi Giovanni , Gulisano Massimo 
Published: July 2008

Abstract

Background
PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.

Methods
In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.

Results
NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.

Conclusion
These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.
Novel sequence variants and a high frequency of recurrent polymorphisms in BRCA1gene in Sri Lankan breast cancer patients and at risk individuals
Authors: De Silva Wasanthi , Karunanayake Eric H , Tennekoon Kamani H , Allen Marie , Amarasinghe Indrani , Angunawala Preethika , Ziard Mohamed H 
Published: July 2008

Abstract

Background
Breast Cancer is the most commonly diagnosed cancer among Sri Lankan women. Germline mutations in the susceptibility genes BRCA1 and BRCA2 in hereditary breast/ovarian cancer, though low in prevalence, are highly penetrant and show geographical variations. There have been only a few reports from Asia on mutations in BRCA1/2 genes and none from Sri Lanka.

Methods
A total of 130 patients with (N = 66) and without (N = 64) a family history of breast cancer, 70 unaffected individuals with a family history of breast cancer and 40 control subjects were analysed for BRCA1 mutations. All but exon 11 were screened by single strand conformation analysis (SSCP) and heteroduplex analysis. PCR products which showed abnormal patterns in SSCP were sequenced. Exon 11 was directly sequenced.

Results
Nineteen sequence variants were found in BRCA1 gene. Two novel deleterious frame-shift mutations; c.3086delT/exon11 (in one patient) and c.5404delG/exon21 (in one patient and two of her family members) were identified. A possibly pathogenic novel missense mutation (c.856T>G/exon 11) and three novel intronic variants (IVS7+36C>T, IVS7+41C>T, IVS7+49del15) were characterised. Ten previously reported common polymorphisms and three previously reported intronic variants were also observed.

Conclusion
After screening of 66 patients with family history and 64 sporadic breast cancer patients, 2 deleterious mutations (c.3086delT and c.5404delG) in two families were identified and two more possibly pathogenic mutations (c.856T>G and IVS17-2A>T) in two families were identified.

Data base

BRCA1 - Gene Bank: Accession # U14680 Version # 14680.1
Overexpression of the riboflavin biosynthetic pathway in Pichia pastoris
Authors: Marx Hans , Mattanovich Diethard , Sauer Michael 
Published: July 2008

AbstractBackgroundHigh cell density cultures ofPichia pastorisgrown on methanol tend to develop yellow colored supernatants, attributed to the release of free flavins. The potential ofP. pastorisfor flavin overproduction is therefore given, but not pronounced when the yeast is grown on glucose. The aim of this study is to characterize the relative regulatory impact of each riboflavin synthesis gene. Deeper insight into pathway control and the potential of deregulation is established by overexpression of the single genes as well as a combined deregulation of up to all six riboflavin synthesis genes.ResultsOverexpression of the first gene of the riboflavin biosynthetic pathway (RIB1) is already sufficient to obtain yellow colonies and the accumulation of riboflavin in the supernatant of shake flask cultures growing on glucose. Sequential deregulation of all the genes, by exchange of their native promoter with the strong and constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP) increases the riboflavin accumulation significantly.ConclusionThe regulation of the pathway is distributed over more than one gene. High cell density cultivations of aP. pastorisstrain overexpressing all sixRIBgenes allow the accumulation of 175 mg/L riboflavin in the supernatant. The basis for rational engineering of riboflavin production inP. pastorishas thus been established.
Nisin inducible production of listeriolysin O in Lactococcus lactis NZ9000
Authors: Bahey-El-Din Mohammed , Griffin Brendan T , Gahan Cormac GM 
Published: July 2008

AbstractBackgroundListeria monocytogenesis a well-characterized food-borne pathogen that infects pregnant women and immunocompromised individuals. Listeriolysin O (LLO) is the major virulence factor of the pathogen and is often used as a diagnostic marker for detection ofL. monocytogenes. In addition, LLO represents a potent antigen driving T cell-mediated immunity during infection. In the present work,Lactococcus lactisNZ9000 was used as an expression host to hyper-produce LLO under inducible conditions using the NICE (NIsin Controlled Expression) system. We created a modified pNZ8048 vector encoding a six-His-tagged LLO downstream of the strong inducible PnisA promoter.ResultsThe constructed vector (pNZPnisA:CYTO-LLO) was expressed inL. lactisNZ9000 and was best induced at mid-log phase with 0.2% v/v nisin for 4 h statically at 30°C. Purification of the His-tagged LLO was accomplished by Ni-NTA affinity chromatography and functionality was confirmed through haemolytic assays. Total LLO yield (measured as total protein content) was 4.43–5.9 mg per litre culture and the haemolytic activity was still detectable after 8 months of storage at 4°C.ConclusionThe LLO production method described in this work provides an approach to efficient LLO production in the Gram-positiveLactococcusbacterium to yield a significant source of the protein for research and diagnostic applications. Expression of LLO inL. lactishas a number of benefits overE. coliwhich may facilitate bothin vivoandin vitroapplications of this system.
Early home treatment of childhood fevers with ineffective antimalarials is deleterious in the outcome of severe malaria
Authors: Orimadegun Adebola E , Amodu Olukemi K , Olumese Peter E , Omotade Olayemi O 
Published: July 2008

Abstract

Background
Early diagnosis and prompt treatment including appropriate home-based treatment of malaria is a major strategy for malaria control. A major determinant of clinical outcome in case management is compliance and adherence to effective antimalarial regimen. Home-based malaria treatment with inappropriate medicines is ineffective and there is insufficient evidence on how this contributes to the outcome of severe malaria. This study evaluated the effects of pre-hospital antimalarial drugs use on the presentation and outcome of severe malaria in children in Ibadan, Nigeria.

Methods
Two hundred and sixty-eight children with a median age of 30 months comprising 114 children with cerebral malaria and 154 with severe malarial anaemia (as defined by WHO) were prospectively enrolled. Data on socio-demographic data, treatments given at home, clinical course and outcome of admission were collected and analysed.

Results
A total of 168 children had treatment with an antimalarial treatment at home before presenting at the hospital when there was no improvement. There were no significant differences in the haematocrit levels, parasite counts and nutritional status of the pre-hospital treated and untreated groups. The most commonly used antimalarial medicine was chloroquine. Treatment policy was revised to Artemesinin-based Combination Therapy (ACT) in 2005 as a response to unacceptable levels of therapeutic failures with chloroquine, however chloroquine use remains high. The risk of presenting as cerebral malaria was 1.63 times higher with pre-hospital use of chloroquine for treatment of malaria, with a four-fold increase in the risk of mortality. Controlling for other confounding factors including age and clinical severity, pre-hospital treatment with chloroquine was an independent predictor of mortality.

Conclusion
This study showed that, home treatment with chloroquine significantly impacts on the outcome of severe malaria. This finding underscores the need for wide-scale monitoring to withdraw chloroquine from circulation in Nigeria and efforts intensified at promoting prompt treatment with effective medicines in the community.