bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension
Authors: Lee Changjin , Mitsialis S. Alex , Aslam Muhammad , Vitali Sally H. , Vergadi Eleni , Konstantinou Georgios , Sdrimas Konstantinos , Fernandez-Gonzalez Angeles , Kourembanas Stella 
Published: November 2012

Background—
Hypoxia induces an inflammatory response in the lung manifested by alternative activation of macrophages with elevation of proinflammatory mediators that are critical for the later development of hypoxic pulmonary hypertension. Mesenchymal stromal cell transplantation inhibits lung inflammation, vascular remodeling, and right heart failure and reverses hypoxic pulmonary hypertension in experimental models of disease. In this study, we aimed to investigate the paracrine mechanisms by which mesenchymal stromal cells are protective in hypoxic pulmonary hypertension.

Methods and Results—
We fractionated mouse mesenchymal stromal cell–conditioned media to identify the biologically active component affecting in vivo hypoxic signaling and determined that exosomes, secreted membrane microvesicles, suppressed the hypoxic pulmonary influx of macrophages and the induction of proinflammatory and proproliferative mediators, including monocyte chemoattractant protein-1 and hypoxia-inducible mitogenic factor, in the murine model of hypoxic pulmonary hypertension. Intravenous delivery of mesenchymal stromal cell–derived exosomes (MEX) inhibited vascular remodeling and hypoxic pulmonary hypertension, whereas MEX-depleted media or fibroblast-derived exosomes had no effect. MEX suppressed the hypoxic activation of signal transducer and activator of transcription 3 (STAT3) and the upregulation of the miR-17 superfamily of microRNA clusters, whereas it increased lung levels of miR-204, a key microRNA, the expression of which is decreased in human pulmonary hypertension. MEX produced by human umbilical cord mesenchymal stromal cells inhibited STAT3 signaling in isolated human pulmonary artery endothelial cells, demonstrating a direct effect of MEX on hypoxic vascular cells.

Conclusion—
This study indicates that MEX exert a pleiotropic protective effect on the lung and inhibit pulmonary hypertension through suppression of hyperproliferative pathways, including STAT3-mediated signaling induced by hypoxia.
On Eddy Viscosity, Energy Cascades, and the Horizontal Resolution of Gridded Satellite Altimeter Products*
Authors: Arbic Brian K. , Polzin Kurt L. , Scott Robert B. , Richman James G. , Shriver Jay F. 
Published: November 2012

Abstract
Motivated by the recent interest in ocean energetics, the widespread use of horizontal eddy viscosity in models, and the promise of high horizontal resolution data from the planned wide-swath satellite altimeter, this paper explores the impacts of horizontal eddy viscosity and horizontal grid resolution on geostrophic turbulence, with a particular focus on spectral kinetic energy fluxes Π(K) computed in the isotropic wavenumber (K) domain. The paper utilizes idealized two-layer quasigeostrophic (QG) models, realistic high-resolution ocean general circulation models, and present-generation gridded satellite altimeter data. Adding horizontal eddy viscosity to the QG model results in a forward cascade at smaller scales, in apparent agreement with results from present-generation altimetry. Eddy viscosity is taken to roughly represent coupling of mesoscale eddies to internal waves or to submesoscale eddies. Filtering the output of either the QG or realistic models before computing Π(K) also greatly increases the forward cascade. Such filtering mimics the smoothing inherent in the construction of present-generation gridded altimeter data. It is therefore difficult to say whether the forward cascades seen in present-generation altimeter data are due to real physics (represented here by eddy viscosity) or to insufficient horizontal resolution. The inverse cascade at larger scales remains in the models even after filtering, suggesting that its existence in the models and in altimeter data is robust. However, the magnitude of the inverse cascade is affected by filtering, suggesting that the wide-swath altimeter will allow a more accurate determination of the inverse cascade at larger scales as well as providing important constraints on smaller-scale dynamics.
Proteolytic Activity by Multiple Bacterial Species Isolated From Chronic Venous Leg Ulcers Degrades Matrix Substrates
Authors: Wysocki Annette B. , Bhalla-Regev Sandhya K. , Tierno Philip M. , Stevens-Riley Marla , Wiygul Ryan-Claire 
Published: November 2012

Background: A major feature of chronic wounds is the loss of tissue, with the exposure of dermal components preventing primary closure and leading to bacterial colonization. Bacterial colonization has been proposed as one of the common underlying pathologies present in chronic wounds. The objective of this exploratory study was to identify bacteria cultured from chronic venous leg ulcers and test for proteolytic activity that degrades matrix substrates. Method: Bacteria were isolated, cultured, and identified from six subjects (average age = 62.8 years) over 2–10 months under an approved protocol using swabs and microbiological culture media. Proteolytic activity against (a) gelatin, (b) an elastin substrate, and (c) a serine/trypsin-sensitive substrate was determined using a colorimetric plate assay with an ELISA plate reader and zymography. Results: We identified 13 bacteria that expressed proteolytic activity against one or more of the tested substrates. Of these, six were Gram-positive ( Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus agalactiae, Corynebacterium, and Streptococcus bovis) and seven were Gram-negative ( Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Morganella morganii, Klebsiella pneumoniae, Bacteroides fragilis, and Serratia marcescens) organisms. Two of these, S. aureus and P. aeruginosa, are recognized wound pathogens. Conclusions: Multiple bacteria species isolated from colonized venous leg ulcers have the capacity to secrete proteases capable of degrading components of the extracellular matrix important for wound healing. Matrix degradation by bacteria may contribute to delays in tissue deposition and repair, suggesting that treatment of chronic wounds should include appropriate management of colonizing bacteria.
Raberite, Tl5Ag4As6SbS15, a new Tl-bearing sulfosalt from Lengenbach quarry, Binn valley, Switzerland: description and crystal structure
Authors: Bindi L. , Nestola F. , Guastoni A. , Peruzzo L. , Ecker M. , Carampin R. 
Published: November 2012

AbstractRaberite, ideally Tl5Ag4As6SbS15, is a new mineral from Lengenbach quarry in the Binn Valley, Valais, Switzerland. It occurs very rarely as euhedral crystals up to 150 m m across associated with yellow needle-like smithite, realgar, hatchite and probable trechmannite, edenharterite, jentschite and two unidentified sulfosalts. Raberite is opaque with a metallic lustre and has a dark brown–red streak. It is brittle with a Vickers hardness (VHN10) of 52 kg mm–2 (range 50–55) corresponding to a Mohs hardness of 2½–3. In reflected light raberite is moderately bireflectant and very weakly pleochroic from light grey to a slightly greenish grey. It is very weakly anisotropic with greyish to light blue rotation tints between crossed polars. Internal reflections are absent. Reflectance percentages for the four COM wavelengths [listed as Rmin, Rmax, (λ)] are 30.6, 31.8 (471.1 nm), 28.1, 29.3 (548.3 nm), 27.1, 28.0 (586.6 nm), and 25.8, 26.9 (652.3 nm).Raberite is triclinic, space group P1, with a = 8.920(1), b = 9.429(1), c = 20.062(3) Å, α = 79.66(1), β = 88.84(1), γ = 62.72(1)º, V = 1471.6(4) Å3 and Z = 2. The crystal structure [R1 = 0.0827 for 2110 reflections with I > 2σ(I)] consists of columns of nine-coordinate Tl atoms forming irregular polyhedra extending along [001] and forming sheets parallel to (010). The columns are decorated by cornersharing MS3 pyramids (M = As, Sb) and linked by AgS3 triangles. Of the seven M positions, one is dominated by Sb and the others by As; the mean M-S bond distances reflect As ↔ Sb substitution at these sites.The eight strongest lines in the powder diffraction pattern [dcalc in Å (I) (hkl)] are: 3.580 (100) (13); 3.506 (58) (23); 3.281 (73) (006); 3.017 (54) (3); 3.001 (98) (133); 2.657 (51) (226); 2.636 (46) (300); 2.591 (57) (330). A mean of 9 electron microprobe analyses gave Tl 39.55(13), Ag 18.42(8), Cu 0.06(2), As 17.08(7), Sb 5.61(6), S 19.15(11); total 99.87 wt.%, which corresponds to Tl4.85Ag4.28Cu0.02As5.72Sb1.16S14.97 with 31 atoms per formula unit. The new mineral has been approved by the IMA-CNMNC Commission (IMA 2012-017) and is named for Thomas Raber, an expert on Lengenbach minerals.
Impaired ribosomal subunit association in Shwachman-Diamond syndrome
Authors: Burwick Nicholas , Coats Scott A. , Nakamura Tomoka , Shimamura Akiko 
Published: November 2012

AbstractShwachman-Diamond syndrome (SDS) is an autosomal-recessive marrow failure syndrome with a predisposition to leukemia. SDS patients harbor biallelic mutations in the SBDS gene, resulting in low levels of SBDS protein. Data from nonhuman models demonstrate that the SBDS protein facilitates the release of eIF6, a factor that prevents ribosome joining. The complete abrogation of Sbds expression in these models results in severe cellular and lethal physiologic abnormalities that differ from the human disease phenotype. Because human SDS cells are characterized by partial rather than complete loss of SBDS expression, we interrogated SDS patient cells for defects in ribosomal assembly. SDS patient cells exhibit altered ribosomal profiles and impaired association of the 40S and 60S subunits. Introduction of a wild-type SBDS cDNA into SDS patient cells corrected the ribosomal association defect, while patient-derived SBDS point mutants only partially improved subunit association. Knockdown of eIF6 expression improved ribosomal subunit association but did not correct the hematopoietic defect of SBDS-deficient cells. In summary, we demonstrate an SBDS-dependent ribosome maturation defect in SDS patient cells. The role of ribosomal subunit joining in marrow failure warrants further investigation.
Gene expression studies of host response to Salmonid alphavirus subtype 3 experimental infections in Atlantic salmon
Authors: Xu Cheng , Guo Tz-Chun , Mutoloki Stephen , Haugland Øyvind , Evensen Øystein 
Published: November 2012

Abstract
Salmonid alphavirus subtype-3 (SAV-3) infection in Atlantic salmon is exclusively found in Norway. The salmonid alphaviruses have been well characterized at the genome level but there is limited information about the host-pathogen interaction phenomena. This study was undertaken to characterize the replication and spread of SAV-3 in internal organs of experimentally infected Atlantic salmon and the subsequent innate and adaptive immune responses. In addition, suitability of a cohabitation challenge model for this virus was also examined. Groups of fish were infected by intramuscular injection (IM), cohabited (CO) or kept uninfected in a separate tank. Samples of pancreas, kidney, spleen, heart and skeletal muscles were collected at 2, 4 and 8 weeks post infection (wpi). Pathological changes were assessed by histology concurrently with viral loads and mRNA expression of immune genes by real time RT-PCR. Pathological changes were only observed in the pancreas and heart (target organs) of both IM and CO groups, with changes appearing first in the pancreas (2 wpi) in the former. Lesions with increasing severity over time coincided with high viral loads despite significant induction of IFN-α, Mx and ISG15. IFN-γ and MHC-I were expressed in all tissues examined and their induction appeared in parallel with that of IL-10. Inflammatory genes TNF-α, IL-12 and IL-8 were only induced in the heart during pathology while T cell-related genes CD3ε, CD4, CD8, TCR-α and MHC-II were expressed in target organs at 8 wpi. These findings suggest that the onset of innate responses came too late to limit virus replication. Furthermore, SAV-3 infections in Atlantic salmon induce Th1/cytotoxic responses in common with other alphaviruses infecting higher vertebrates. Our findings demonstrate that SAV-3 can be transmitted via the water making it suitable for a cohabitation challenge model.
Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging
Authors: Barna János , Princz Andrea , Kosztelnik Mónika , Hargitai Balázs , Takács-Vellai Krisztina , Vellai Tibor 
Published: November 2012

Abstract

Background
Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown.

Results
We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation.

Conclusion
Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.
smRNAome profiling to identify conserved and novel microRNAs in Stevia rebaudiana Bertoni
Authors: Mandhan Vibha , Kaur Jagdeep , Singh Kashmir 
Published: November 2012

Abstract

Background
MicroRNAs (miRNAs) constitute a family of small RNA (sRNA) population that regulates the gene expression and plays an important role in plant development, metabolism, signal transduction and stress response. Extensive studies on miRNAs have been performed in different plants such as Arabidopsis thaliana, Oryza sativa etc. and volume of the miRNA database, mirBASE, has been increasing on day to day basis. Stevia rebaudiana Bertoni is an important perennial herb which accumulates high concentrations of diterpene steviol glycosides which contributes to its high indexed sweetening property with no calorific value. Several studies have been carried out for understanding molecular mechanism involved in biosynthesis of these glycosides, however, information about miRNAs has been lacking in S. rebaudiana. Deep sequencing of small RNAs combined with transcriptomic data is a powerful tool for identifying conserved and novel miRNAs irrespective of availability of genome sequence data.

Results
To identify miRNAs in S. rebaudiana, sRNA library was constructed and sequenced using Illumina genome analyzer II. A total of 30,472,534 reads representing 2,509,190 distinct sequences were obtained from sRNA library. Based on sequence similarity, we identified 100 miRNAs belonging to 34 highly conserved families. Also, we identified 12 novel miRNAs whose precursors were potentially generated from stevia EST and nucleotide sequences. All novel sequences have not been earlier described in other plant species. Putative target genes were predicted for most conserved and novel miRNAs. The predicted targets are mainly mRNA encoding enzymes regulating essential plant metabolic and signaling pathways.

Conclusions
This study led to the identification of 34 highly conserved miRNA families and 12 novel potential miRNAs indicating that specific miRNAs exist in stevia species. Our results provided information on stevia miRNAs and their targets building a foundation for future studies to understand their roles in key stevia traits.
Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival
Authors: Sung Hyuna , Jeon Sujee , Lee Kyoung-Mu , Han Sohee , Song Minkyo , Choi Ji-Yeob , Park Sue K , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee 
Published: November 2012

Abstract

Background
Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown.

Methods
We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died.

Results
Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07).

Conclusions
Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.
Association between body size and blood pressure in children from different ethnic origins
Authors: LA de Hoog Marieke , van Eijsden Manon , Stronks Karien , Gemke Reinoud JBJ , Vrijkotte Tanja GM 
Published: November 2012

Abstract

Objective
To assess associations between body size and blood pressure in children (5-6 years) from different ethnic origins.

Method
Five ethnic groups of the ABCD cohort were examined: Dutch (n=1 923), Turkish (n=99), Moroccan (n=187), Black-African (n=67) and Black-Caribbean (n=121). Data on body-mass-index (BMI), waist-to-height ratio (WHtR), fat-mass-index (FMI), and systolic blood pressure (SBP) and diastolic blood pressure (DBP), were collected. Linear regression analysis with restricted cubic splines was used to examine non-linear associations between body size and blood pressure, adjusted for age, sex, height and birth weight.

Results
Ethnic differences were found in associations of BMI with SBP and DBP (SBP: p=0.001 and DBP: p=0.01) and FMI with SBP (p=0.03). BMI and FMI had a relatively large positive association with SBP in Turkish children (BMI: β=2.46mmHg; 95%CI:1.20-3.72; FMI: β=2.41mmHg; 95%CI:1.09-3.73) compared to Dutch (BMI: β=1.31mmHg; 95%CI:0.71-1.92; FMI: β=0.84mmHg; 95%CI:0.23-1.45). Black-Caribbean and Moroccan children showed high blood pressure with low BMI and FMI. Moroccan children showed higher SBP with high BMI and FMI. WHtR was positively associated with SBP and DBP, similar in all ethnic groups. Generally, strongest associations with blood pressure were found for BMI in all ethnic groups.

Conclusion
Ethnic-specific associations between BMI, and FMI and blood pressure are present at young age, with Turkish children showing the highest increase in blood pressure with increasing body size. The higher blood pressure in the Black-Caribbean and Moroccan children with low BMI needs further research. WHtR or FMI do not seem to be associated more strongly to blood pressure than BMI in any ethnic group.
Alzheimer's disease biomarker discovery using in silico literature mining and clinical validation
Authors: Greco Ines , Day Nicola , Riddoch-Contreras Joanna , Reed Jane , Soininen Hilkka , Kłoszewska Iwona , Tsolaki Magda , Vellas Bruno , Spenger Christian , Mecocci Patrizia , Wahlund Lars-Olof , Simmons Andrew , Barnes Julie , Lovestone Simon 
Published: November 2012

Abstract

Background
Alzheimer’s Disease (AD) is the most widespread form of dementia in the elderly but despite progress made in recent years towards a mechanistic understanding, there is still an urgent need for disease modification therapy and for early diagnostic tests. Substantial international efforts are being made to discover and validate biomarkers for AD using candidate analytes and various data-driven 'omics' approaches. Cerebrospinal fluid is in many ways the tissue of choice for biomarkers of brain disease but is limited by patient and clinician acceptability, and increasing attention is being paid to the search for blood-based biomarkers. The aim of this study was to use a novel in silico approach to discover a set of candidate biomarkers for AD.

Methods
We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of assertional metadata derived from relevant legacy information. We then assessed the validity of this approach using direct assays of the identified biomarkers in plasma by immunodetection methods.

Results
Using this in silico approach, we identified 25 biomarker candidates, at least three of which have subsequently been reported to be altered in blood or CSF from AD patients. Two further candidate biomarkers, indicated from the in silico approach, were choline acetyltransferase and urokinase-type plasminogen activator receptor. Using immunodetection, we showed that, in a large sample set, these markers are either altered in disease or correlate with MRI markers of atrophy.

Conclusions
These data support as a proof of concept the use of data mining and in silico analyses to derive valid biomarker candidates for AD and, by extension, for other disorders.