julilili42/papers huggingface dataset:
A Collagen-based Scaffold Delivering Exogenous MicroRNA-29B to Modulate Extracellular Matrix Remodeling
2014-01-09

Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.
Bronchopulmonary sequestration with massive pleural effusion: pleuroamniotic shunting vs intrafetal vascular laser ablation
2014-01-09

ABSTRACT Objective To assess the incidence of complications among a relatively large cohort of fetuses with bronchopulmonary sequestration (BPS) and the success of two different intrauterine treatment modalities. Methods All cases with a prenatal diagnosis of BPS detected in a 10‐year period (2002–2011) in two tertiary referral centers were reviewed retrospectively for intrauterine course and outcome. Up to May 2010 severe pleural effusions were treated with pleuroamniotic shunting. Thereafter, they were treated with ultrasound‐guided laser coagulation of the feeding artery. Results A total of 41 fetuses with BPS were included in the study. In 29 (70.7%) there was no pleural effusion or hydrops and they were treated conservatively. In 19/29 (65.5%) there was partial or complete regression of the lesion during the course of pregnancy. All were born alive (median age at delivery, 38.3 (interquartile range (IQR), 34.0–39.6) weeks) and 16 (55.2%) required sequestrectomy. Intrauterine intervention was performed in all 12 (29.3%) fetuses with pleural effusion. Seven fetuses were treated with pleuroamniotic shunting. One fetus with severe hydrops died in utero . There was no complete regression in any case of BPS in this group. Six infants were born alive (median age, 37.2 (IQR, 30.3–37.4) weeks), of which five (83.3%) required sequestrectomy. Five fetuses were treated with laser ablation of the feeding vessel. In all cases of BPS there was regression after laser ablation. All infants were delivered at term (median age, 39.1 (IQR, 38.0–40.0) weeks). One (20.0%) neonate required sequestrectomy after birth. Following intrauterine shunt placement complete regression of the lesion was significantly less frequent (0/7 (0%) with shunt placement vs 4/5 (80%) with intrafetal laser treatment) and gestational age at birth was significantly lower, compared to treatment with intrafetal laser. Complete regression of the lesion was also significantly more frequent in the laser group compared to cases without intervention. Conclusion In the absence of pleural effusion, the likelihood of spontaneous regression of BPS is high and the prognosis is therefore favorable. In cases with massive pleural effusion, treatment by laser ablation of the feeding vessel seems to be more effective than is pleuroamniotic shunting, with fewer complications. It might also reduce the need for postnatal surgery. Copyright © 2014 ISUOG. Published by John Wiley &amp; Sons Ltd.
Screening of mutations in GNAL in sporadic dystonia patients
2014-01-09

ABSTRACT Background GNAL mutations have been shown to cause adult‐onset isolated dystonia, a disabling movement disorder characterized by involuntary muscle contractions causing twisting and repetitive movements or abnormal postures. Methods To test the frequency of GNAL mutations in a series of 137 German patients with sporadic dystonia patients we used next‐generation sequencing of amplicon‐derived barcoded NexteraXT libraries for the coding exons and adjacent intronic sequences of GNAL . Results In our cohort we identified 1 pathogenic nonsense mutation (c.733C&gt;T, p.R245*) in a patient with cervical dystonia. In a second patient a synonymous coding nonsynonymous variant (c.G252A, p.E84E) was detected, which is predicted to alter a splice site. Conclusions Our findings further support GNAL as causative gene in adult‐onset isolated dystonia. © 2014 International Parkinson and Movement Disorder Society
A Cognitively Grounded Measure of Pronunciation Distance
2014-01-09

In this study we develop pronunciation distances based on naive discriminative learning (NDL). Measures of pronunciation distance are used in several subfields of linguistics, including psycholinguistics, dialectology and typology. In contrast to the commonly used Levenshtein algorithm, NDL is grounded in cognitive theory of competitive reinforcement learning and is able to generate asymmetrical pronunciation distances. In a first study, we validated the NDL-based pronunciation distances by comparing them to a large set of native-likeness ratings given by native American English speakers when presented with accented English speech. In a second study, the NDL-based pronunciation distances were validated on the basis of perceptual dialect distances of Norwegian speakers. Results indicated that the NDL-based pronunciation distances matched perceptual distances reasonably well with correlations ranging between 0.7 and 0.8. While the correlations were comparable to those obtained using the Levenshtein distance, the NDL-based approach is more flexible as it is also able to incorporate acoustic information other than sound segments.
Stiffness, Pain, and Hip Muscle Strength Are Factors Associated With Self-reported Physical Disability in Hip Osteoarthritis
2014-01-09

Stiffness, pain, and hip muscle strength are associated with self-reported PD in hip OA. It is imperative that exercise treatments for hip OA include strategies to modify these factors. Further research should evaluate their role in preventing hip OA.
Chemo‐enzymatic three‐fragment assembly of semisynthetic proteins
2014-01-09

Here, we report the development of a method for three‐fragment assemblies of semisynthetic proteins by combining sortase‐mediated ligation with site‐specific bioconjugation catalyzed by the 4′‐phosphopantetheine transferase Sfp. This method enables the introduction of synthetic peptides into central regions of proteins without the need to purify intermediates. The assembled proteins are linked at the N‐terminal junction with a 4′‐phosphopantetheine moiety and with a peptide bond at the C‐terminal ligation site. We have demonstrated the applicability of this method by assembling a semisynthetic model protein derived from fluorescence resonance energy transfer‐based reporters from three fragments in a one‐pot reaction. Copyright © 2014 European Peptide Society and John Wiley &amp; Sons, Ltd.
A Mouse Bone Marrow Stromal Cell Line with Skeletal Stem Cell Characteristics to Study Osteogenesis In Vitro and In Vivo
2014-01-09

Bone marrow stromal cells (BMSCs) are composed of progenitor and multipotent skeletal stem cells, which are able to differentiate in vitro into osteocytes, adipocytes, and chondrocytes. Mouse BMSCs (mBMSCs) are a versatile model system to investigate factors involved in BMSC differentiation in vitro and in vivo as a variety of transgenic mouse models are available. In this study, mBMSCs were isolated and osteogenic differentiation was investigated in tissue culture and in vivo. Three out of seven independent cell isolates showed the ability to differentiate into osteocytes, adipocytes, and chondrocytes in vitro. In vitro multipotency of an established mBMSC line was maintained over 45 passages. The osteogenic differentiation of this cell line was confirmed by quantitative polymerase chain reaction (qPCR) analysis of specific markers such as osteocalcin and shown to be Runx2 dependent. Notably, the cell line, when transplanted subcutaneously into mice, possesses full skeletal stem cell characteristics in vivo in early and late passages, evident from bone tissue formation, induction of vascularization, and hematopoiesis. This cell line provides, thus, a versatile tool to unravel the molecular mechanisms governing osteogenesis in vivo thereby aiding to improve current strategies in bone regenerative therapy.
Identification of short terminal motifs enriched by antibodies using peptide mass fingerprinting
2014-01-09

Abstract Motivation: Mass spectrometry-based protein profiling has become a key technology in biomedical research and biomarker discovery. Sample preparation strategies that reduce the complexity of tryptic digests by immunoaffinity substantially increase throughput and sensitivity in proteomic mass spectrometry. The scarce availability of peptide-specific capture antibodies limits these approaches. Recently antibodies directed against short terminal motifs were found to enrich subsets of peptides with identical terminal sequences. This approach holds the promise of a significant gain in efficiency. TXP (Triple X Proteomics) and context-independent motif specific/global proteome survey binders are variants of this concept. Principally the binding motifs of such antibodies have to be elucidated after generating these antibodies. This entails a substantial effort in the lab, as it requires synthetic peptide libraries and numerous mass spectrometry experiments. Results: We present an algorithm for predicting the antibody-binding motif in a mass spectrum obtained from a tryptic digest of a common cell line after immunoprecipitation. The epitope prediction, based on peptide mass fingerprinting, reveals the most enriched terminal epitopes. The tool provides a P-value for each potential epitope, estimated by sampling random spectra from a peptide database. The second algorithm combines the predicted sequences to more complex binding motifs. A comparison with library screenings shows that the predictions made by the novel methods are reliable and reproducible indicators of the binding properties of an antibody. Availability: Mass spectrum data, predictions, sampling tables, consensus peptide databases and the applied protocols are available as Supplementary Material. TXP-Terminus Enrichment Analysis (TEA) and MATERICS (Mass-spectrometric Analysis of Terminal Epitope Enrichment in Complex Samples) are available as web services at http://webservices.nmi.de/materics. Contact: hannes.planatscher@nmi.de Supplementary information: Supplementary data are available at Bioinformatics online.
Modal particles in rationale clauses and related constructions
2014-01-09

This paper discusses the connection between sentential modality (e.g. the modality introduced by a modal auxiliary such as may or must ) and the force of an utterance. This connection is explored with a focus on the German particles ruhig / bloß / JA , which typically occur in modalized declaratives and in imperatives, indicating a connection between the two types of utterances. This paper poses the question of how to account for such particles in rationale clauses, which cannot be trivially analyzed as modalized declaratives or imperatives. I pursue a uniform analysis of ruhig / bloß / JA as ‘modal modifiers’ (in the spirit of Grosz 2010, 2011), which increase the strength of a modal utterance; I argue that rationale clauses (on a par with imperatives) contain a covert modal that is best characterized as an existential modal with a modal choice function, in the spirit of Rullmann et al. (2008).
Draft Genome Sequence of Streptomyces niveus NCIMB 11891, Producer of the Aminocoumarin Antibiotic Novobiocin
2014-01-10

ABSTRACT Streptomyces niveus NCIMB 11891 is the producer of the gyrase inhibitor novobiocin, which belongs to the aminocoumarin class of antibiotics. The genome sequence of this strain was found to contain, besides the gene cluster for novobiocin, a putative gene cluster for the macrolactam antibiotic BE-14106 and further secondary metabolite gene clusters.
Genome Sequence of the Mycorrhizal Helper Bacterium Pseudomonas fluorescens BBc6R8
2014-01-10

ABSTRACT We report the draft genome sequence of the mycorrhizal helper bacterium Pseudomonas fluorescens strain BBc6R8. This is the first genome of a mycorrhizal helper bacterium. The draft genome contains 6,952,353 bp and is predicted to encode 6,317 open reading frames. Comparative genomic analyses will help to identify helper traits.
Toll-like receptor genetic variants and colorectal cancer
2014-01-10

Single-nucleotide polymorphisms in Toll-like receptor 5 (<i>TLR5</i>), encoding a sensor for flagellin, have been shown to influence cytokine responses to intestinal bacteria and to be associated with significant alterations in the survival of colorectal carcinoma (CRC) patients. These findings point to a link between TLRs and CRC that may have both therapeutic and prognostic/predictive implications.
Draft Genome Sequence of Streptomyces roseochromogenes subsp. oscitans DS 12.976, Producer of the Aminocoumarin Antibiotic Clorobiocin
2014-01-10

ABSTRACT Streptomyces roseochromogenes subsp. oscitans DS 12.976 is the producer of the gyrase-inhibiting aminocoumarin antibiotic clorobiocin. Here, we present a draft genome sequence of this strain, in which we identified the clorobiocin gene cluster as well as an unusually high number (43) of further putative secondary metabolite clusters.
Climate change and tectonic uplift triggered the formation of the Atacama Desert’s giant nitrate deposits
2014-01-11

The giant nitrate deposits of the hyperarid Atacama Desert (Chile) are one of the most extraordinary, yet enigmatic, mineral occurrences on Earth. These deposits are complex assemblages of highly soluble nitrates, chlorides, sulfates, perchlorates, iodate
Prestimulus oscillatory power and connectivity patterns predispose conscious somatosensory perception
2014-01-13

Significance Experimental use of near-threshold stimuli is regarded as an important approach to study neural processes leading to conscious access (defined in operational terms as “reportability”). Looking to what extent prestimulus periods contribute to the variability of perceptual states has become increasingly popular, frequently pointing to an increased excitability of relevant sensory regions. Here, we aim to extend this “local” perspective by a network approach. A framework called “Windows to Consciousness” is introduced. We postulate that along with an enhanced excitability, preestablished pathways of information flow are a crucial ingredient, determining whether an upcoming near-threshold stimulus will be consciously perceived. Using magnetoencephalography combined with state-of-the-art source-imaging approaches, we are able to report supportive evidence.
Indications and Limits for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Lessons Learned from 15 Cases at a Single Centre
2014-01-13

The actual high morbidity and mortality rates related to the ALPPS procedure should lead us to a more cautious selection of the candidates for this operation and restriction of the indications through an accurate work-up based on interdisciplinary cooperation among hepatologists, oncologists, radiologists and surgeons.
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood
2014-01-13

Background and objectives The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer‐reviewed evidence‐based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. Methods This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force. Diagnosis If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia ( SCA ) 1, 2, 3, 6, 7 and 17 (level B ), and in Asian patients also for dentatorubral‐pallidoluysian atrophy ( DRPLA ). In the case of recessive disease, a stepwise diagnostic work‐up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at F riedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene ( POLG gene, various mutations), autosomal recessive spastic ataxia of C harlevoix− S aguenay ( ARSACS ) and ataxia with oculomotor apraxia ( AOA ) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work‐up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 FMR 1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work‐up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work‐up, or even whole exome and genome sequencing for selected cases. Treatment Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in F riedreich's ataxia (level A ). Riluzole (level B ) and amantadine (level C ) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA 3 patients (level B ) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.
Luther’s Transformation of Medieval Thought
2014-01-13

Luther's continuity with his past appears in an unbroken line in von Staupitz's pastoral counsel, his use of exegetical resources, his use of church history for support of his arguments; parallels with medieval thought and practice occurred in his concept of the two realms and justification; his view of the universal priesthood represents a transformation of elements in mystical steams of thought and Ockham; his distinction of law and gospel parallels certain mystical expressions. Luther's concept of grace arose in a complex recombination of elements in these same sources. Luther creatively adopted, adapted, and transformed components of various medieval ways of thought.
Sonoelastography Usage Among German DEGUM-Certified Breast Ultrasound Specialists
2014-01-13

Sonoelastography is a feasible and helpful method in the evaluation of breast lesions. A significant number of German ultrasound specialists already apply this technology today. We expect a growing number of sonographers to perform sonoelastography in the near future, provided that they have the necessary ultrasound system and that they are trained in the method. Evidence from the literature and the recommendations of the medical societies support this development.
Simultaneous isolation of primary human hepatocytes and non-parenchymal liver cells for the establishment of functional co-culture and tissue engineering liver models
2014-01-13

Primary human hepatocytes (PHH) are parenchymal liver cells and represent ̃60 to 70% of total liver cells. Additionally non-parenchymal cells (NPC) like Kupffer cells (KC), Stellate cells (SC), cholangiocytes (CC) and sinusoidal endothelial cells (SEC) are present in the liver. NPC play a central role in many pathophysiologies of the liver, such as drug induced liver diseases, inflammation, liver fibrosis and cirrhosis as well as in regenerative processes. Many in vitro liver models are based on a monoculture of PHH and thus, the influence of NPC is missing. In recent years, NPC have become more relevant for the development of liver co-culture models and in tissue engineering. However, only few protocols are dealing with the isolation of NPC are available in literature. Therefore the aim of the present study was the establishment of protocols for the simultaneous isolation of NPC from human tissue in a high quality and purity.
Comparison of the response of primary rat and human hepatocytes to ethanol exposition in a miniaturized three-dimensional (3D) multi-compartment bioreactor system
2014-01-13

Various studies indicate that the accumulation of reactive oxygen species (ROS) and associated cellular damage play an important role in ageing of various organs, including the liver. Especially high concentrations of ethanol lead to oxidative damage, which have been proposed as the major cause of cellular ageing and death. To analyze these effects a bioreactor technology for in vitro liver cell culture was used, which is based on a perfused hollow-fibre capillary network offering dynamic three-dimensional culture conditions with continuous medium perfusion and decentralized oxygenation. This technology creates an in vitro situation, which is close to the physiological conditions in vivo.
A story about hepatic inflammatory and regenerative processes: An in vitro model of liver damage shows influence from hepatic tissue quality and donor anamnesis
2014-01-13

Hepatic tissue damage can occur due to several diseases like cholestasis, infections or liver tumors. Kupffer cells (KC) play an important role in mediating tissue damage as well as regenerative processes. KC activation by lipopolysaccharide (LPS), antigens or endogenous proteins such as released under necrotic conditions can lead to an activation of the NF-κB signaling pathway transmitted by reactive oxygen intermediates (ROI). Once activated, KC release different cytokine patterns that support inflammation or induce tolerance reactions. Aim of the present study was the establishment of a human in vitro model for the simulation of hepatic tissue damage which enables the investigation of immune mediated signaling in hepatic inflammatory reactions.
The Serum Reponse Factor (SRF) is involved in the transcriptional upregulation of the functional p53 inhibitor MDM 4 in hepatocellular carcinoma
2014-01-13

MDM 4 is a p53 binding protein that negatively regulates p53-dependent transcription. MDM 4 was found overexpressed in a variety of human cancers and amplifications of the MDM 4 gene locus were reported most of these tumor entities. We have previously demonstrated that MDM 4 is upregulated in about 50% of human hepatocellular carcinomas (HCC), both at messenger RNA (mRNA) and protein level. Although we identified 1q32 gains as a mechanism leading to MDM 4 overexpression in human HCC, many liver tumors display a balanced MDM 4 gene locus. Thus, additional mechanisms are responsible for aberrant MDM 4 expression in the presence of a diploid MDM 4 gene locus. The transcriptional regulation of MDM 4 remains largely elusive. Here, we show that overexpression of SRF is involved in the transcriptional upregulation of MDM 4 in HCC thereby supporting its protumorigenic function.