bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative ultrasonography of facial muscles in patients with chronic facial palsy
Authors: Volk Gerd Fabian , Pohlmann Martin , Sauer Maik , Finkensieper Mira , Guntinas‐Lichius Orlando 
Published: December 2013

AbstractIntroduction: In this study we introduce quantitative facial muscle ultrasound as a diagnostic tool for patients with chronic unilateral facial palsy. Methods: Muscle area, thickness, and echo intensity of 6 facial muscles (frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis) and of 2 chewing muscles (temporalis and masseter, as controls) were measured in 20 patients with chronic facial palsy. Results: Aside from 1, all facial muscles were significantly smaller on the paralyzed side. With exception of frontalis and orbicularis oculi muscles, all other facial muscles showed significantly higher echo intensity on the affected side. Muscle size and echo intensity of the chewing muscles showed no side‐to‐side asymmetry. Conclusions: Quantitative ultrasound of facial muscles helps to better characterize their status in patients with chronic facial palsy in the phase of denervation and during regeneration. Muscle Nerve 50: 358–365, 2014
Altered tibial nerve biomechanics in patients with diabetes mellitus
Authors: Boyd Benjamin S. , Dilley Andrew 
Published: December 2013

ABSTRACTIntroduction: Hyperglycemia associated with diabetes mellitus (DM) has adverse impacts on peripheral nerve connective tissue structure, and there is preliminary evidence that nerve biomechanics may be altered. Methods: Ultrasound imaging was utilized to quantify the magnitude and timing of tibial nerve excursion during ankle dorsiflexion in patients with DM and matched healthy controls. Results: Tibial nerve longitudinal excursion at the ankle and knee was reduced, and timing was delayed at the ankle in the DM group. Severity of neuropathy was correlated with larger reductions in longitudinal excursion. Nerve cross‐sectional area was increased at the ankle in the DM group. Conclusions: Larger tibial nerve size within the tarsal tunnel in patients with DM may restrict longitudinal excursion, which was most evident with more severe neuropathy. It is hypothesized that these alterations may be related to painful symptoms during functional activities that utilize similar physiological motions through various biomechanical and physiological mechanisms. Muscle Nerve 50:216–223, 2014
A deluxe FETI‐DP algorithm for a hybrid staggered discontinuous Galerkin method for H(curl)‐elliptic problems
Authors: Chung Eric T. , Kim Hyea Hyun 
Published: December 2013

SUMMARYConvergence theories and a deluxe dual and primal finite element tearing and interconnecting algorithm are developed for a hybrid staggered DG finite element approximation of H(curl) elliptic problems in two dimensions. In addition to the advantages of staggered DG methods, the basis functions of the new hybrid staggered DG method are all locally supported in the triangular elements, and a Lagrange multiplier approach is applied to enforce the global connections of these basis functions. The interface problem on the Lagrange multipliers is further reduced to the resulting problem on the subdomain interfaces, and a dual and primal finite element tearing and interconnecting algorithm with an enriched weight factor is then applied to the resulting problem. Our algorithm is shown to give a condition number bound of C(1 + log(H ∕ h))2, independent of the two parameters, where H ∕ h is the number of triangles across each subdomain. Numerical results are included to confirm our theoretical bounds. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of TP53 mutational status on gene expression patterns across 10 human cancer types
Authors: Parikh Neha , Hilsenbeck Susan , Creighton Chad J , Dayaram Tajhal , Shuck Ryan , Shinbrot Eve , Xi Liu , Gibbs Richard A , Wheeler David A , Donehower Lawrence A 
Published: December 2013

AbstractMutations in the TP53 tumour suppressor gene occur in half of all human cancers, indicating its critical importance in inhibiting cancer development. Despite extensive studies, the mechanisms by which mutant p53 enhances tumour progression remain only partially understood. Here, using data from the Cancer Genome Atlas (TCGA), genomic and transcriptomic analyses were performed on 2256 tumours from 10 human cancer types. We show that tumours with TP53 mutations have altered gene expression profiles compared to tumours retaining two wild‐type TP53 alleles. Among 113 known p53‐up‐regulated target genes identified from cell culture assays, 10 were consistently up‐regulated in at least eight of 10 cancer types that retain both copies of wild‐type TP53. RPS27L, CDKN1A (p21CIP1) and ZMAT3 were significantly up‐regulated in all 10 cancer types retaining wild‐type TP53. Using this p53‐based expression analysis as a discovery tool, we used cell‐based assays to identify five novel p53 target genes from genes consistently up‐regulated in wild‐type p53 cancers. Global gene expression analyses revealed that cell cycle regulatory genes and transcription factors E2F1, MYBL2 and FOXM1 were disproportionately up‐regulated in many TP53 mutant cancer types. Finally, > 93% of tumours with a TP53 mutation exhibited greatly reduced wild‐type p53 messenger expression, due to loss of heterozygosity or copy neutral loss of heterozygosity, supporting the concept of p53 as a recessive tumour suppressor. The data indicate that tumours with wild‐type TP53 retain some aspects of p53‐mediated growth inhibitory signalling through activation of p53 target genes and suppression of cell cycle regulatory genes. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk
A novel SERPINE1–FOSB fusion gene results in transcriptional up‐regulation of FOSB in pseudomyogenic haemangioendothelioma
Authors: Walther Charles , Tayebwa Johnbosco , Lilljebjörn Henrik , Magnusson Linda , Nilsson Jenny , von Steyern Fredrik Vult , Øra Ingrid , Domanski Henryk A , Fioretos Thoas , Nord Karolin H , Fletcher Christopher DM , Mertens Fredrik 
Published: December 2013

AbstractPseudomyogenic haemangioendothelioma (PHE) is an intermediate malignant vascular soft tissue tumour primarily affecting children and young adults. The molecular basis of this neoplasm is unknown. We here used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT–PCR and quantitative real‐time PCR on a series of morphologically well‐characterized PHEs to show that a balanced translocation, t(7;19)(q22;q13), detected as the sole cytogenetic aberration in two cases, results in fusion of the SERPINE1 and FOSB genes. This translocation has not been observed in any other bone or soft tissue tumour. Interphase FISH on sections from eight additional PHEs identified the same SERPINE1–FOSB fusion in all cases. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB, which was found to be expressed at higher levels in PHEs than in other soft tissue tumours. FOSB encodes a transcription factor belonging to the FOS family of proteins, which, together with members of the JUN family of transcription factors, are major components of the activating protein 1 (AP‐1) complex. Further studies are needed to understand the cellular impact of the aberrant expression of the FOSB gene, but as the t(7;19) resulting in the SERPINE1–FOSB fusion seems to be pathognomonic for PHE, FISH or RT–PCR could be useful for differential diagnostic purposes. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk
Flightless I over‐expression impairs skin barrier development, function and recovery following skin blistering
Authors: Kopecki Zlatko , Yang Gink N , Arkell Ruth M , Jackson Jessica E , Melville Elizabeth , Iwata Hiroaki , Ludwig Ralf J , Zillikens Detlef , Murrell Dedee F , Cowin Allison J 
Published: December 2013

AbstractDevelopment of an intact epidermis is critical for maintaining the integrity of the skin. Patients with epidermolysis bullosa (EB) experience multiple erosions, which breach the epidermal barrier and lead to increased microbial colocalization of wounds, infections and sepsis. The cytoskeletal protein Flightless I (Flii) is a known regulator of both development and wound healing. Using Flii+/−, WT and FliiTg/Tg mice, we investigated the effect of altering Flii levels in embryos and adult mice on the development of the epidermal barrier and, consequently, how this affects the integrity of the skin in EB. Flii over‐expression resulted in delayed formation of the epidermal barrier in embryos and decreased expression of tight junction (TJ) proteins Claudin‐1 and ZO‐2. Increased intercellular space and transepidermal water loss was observed in FliiTg/Tg adult mouse skin, while FliiTg/Tg keratinocytes showed altered TJ protein localization and reduced transepithelial resistance. Flii is increased in the blistered skin of patients with EB, and over‐expression of Flii in experimental EBA showed impaired Claudin‐1 and ‐4 TJ protein expression and delayed recovery of functional barrier post‐blistering. Immunoprecipitation confirmed Flii associated with TJ proteins and in vivo actin assays showed that the effect of Flii on actin polymerization underpinned the impaired barrier function observed in FliiTg/Tg mice. These results therefore demonstrate an important role for Flii in the development and regulation of the epidermal barrier, which may contribute to the impaired healing and skin fragility of EB patients. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Engineering a soluble parathyroid hormone GPCR mimetic
Authors: Audu Christopher O. , Plati Jessica J. , Pellegrini Maria , Mierke Dale F. 
Published: December 2013

ABSTRACTWe designed and characterized a soluble mimic of the parathyroid hormone (PTH) receptor (PTH1R) that incorporates the N‐terminus and third extracellular loop of PTH1R, important for ligand binding. The engineered receptor (PTH1R‐NE3) was conceived to enable easy production and the use of standard biochemical and biophysical assays for the screening of competitive antagonists of PTH. We show that PTH1R‐NE3 is folded, thermodynamically stable and selectively binds PTH. We also demonstrate the utility of our mimic by identifying a small molecule that competes with PTH in our PTH1R‐NE3‐based fluorescence polarization assay. Antagonists to PTH1R, a transmembrane protein belonging to the class B G‐protein coupled receptor family, may provide new therapeutic options for calcium metabolism diseases like humoral hypercalcemia of malignancy. Proteins 2014; 82:1370–1375. © 2013 Wiley Periodicals, Inc.
Crystal structures of carbohydrate recognition domain of blood dendritic cell antigen‐2 (BDCA2) reveal a common domain‐swapped dimer
Authors: Nagae Masamichi , Ikeda Akemi , Kitago Yu , Matsumoto Naoki , Yamamoto Kazuo , Yamaguchi Yoshiki 
Published: December 2013

ABSTRACTWe report on crystal structures of a carbohydrate recognition domain (CRD) of human C‐type lectin receptor blood dendritic cell antigen‐2 (BDCA2). Three different crystal forms were obtained at 1.8–2.3 Å resolution. In all three, the CRD has a basic C‐type lectin fold, but a long loop extends away from the core domain to form a domain‐swapped dimer. The structures of the dimers from the three different crystal forms superimpose well, indicating that domain swapping and dimer formation are energetically stable. The structure of the dimer is compared with other domain‐swapped proteins, and a possible regulation mechanism of BDCA2 is discussed. Proteins 2014; 82:1512–1518. © 2013 Wiley Periodicals, Inc.
Street Vending Phenomena: A Literature Review and Research Agenda
Authors: Wongtada Nittaya 
Published: December 2013

AbstractStreet vending is pervasive across the globe, especially in developing countries. It provides an important source of earnings for the unemployed in urban areas, as well as a source of relatively inexpensive goods and services for city residents. However, typical street vendors face a common set of problems, which range from tenuous property rights and harassment from civic authorities to subsistence living and earning. Under this precarious setting, street enterprises have been expanding. The objective of this article is to employ a systematic method to research the studies in this field, extract their findings, and integrate them in order to propose a model that incorporates factors affecting the success of street enterprises. Based on this model, major research issues are outlined to advance the knowledge in the field. © 2013 Wiley Periodicals, Inc.
High precision micro-impulse measurements for micro-thrusters based on torsional pendulum and sympathetic resonance techniques
Authors: Zhang Daixian , Wu Jianjun , Zhang Rui , Zhang Hua , He Zhen 
Published: December 2013

A sympathetic resonance theory is analyzed and applied in a newly developed torsional pendulum to measure the micro-impulse produced by a μN s-class ablative pulsed plasma thruster. According to theoretical analysis on the dynamical behaviors of a torsional pendulum, the resonance amplification effect of micro-signals is presented. In addition, a new micro-impulse measurement method based on sympathetic resonance theory is proposed as an improvement of the original single pulse measurement method. In contrast with the single pulse measurement method, the advantages of sympathetic resonance method are significant. First, because of the magnification of vibration signals due to resonance processes, measurement precision for the sympathetic resonance method becomes higher especially in reducing reading error. With an increase in peak number, the relative errors induced by readout of voltage signals decrease to approximately ±1.9% for the sympathetic resonance mode, whereas the relative error in single pulse mode is estimated as ±13.4%. Besides, by using the resonance amplification effect the sympathetic resonance method makes it possible to measure an extremely low-impulse beyond the resolution of a thrust stand without redesigning or purchasing a new one. Moreover, because of the simple operational principle and structure the sympathetic resonance method is much more convenient and inexpensive to be implemented than other high-precision methods. Finally, the sympathetic resonance measurement method can also be applied in other thrust stands to improve further the ability to measure the low-impulse bits.
Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach
Authors: You Sungyong , Yoo Seung-Ah , Choi Susanna , Kim Ji-Young , Park Su-Jung , Ji Jong Dae , Kim Tae-Hwan , Kim Ki-Jo , Cho Chul-Soo , Hwang Daehee , Kim Wan-Uk 
Published: December 2013

Significance
Rheumatoid arthritis (RA) is an autoimmune disorder that affects ∼1% of the population. Macrophage- and fibroblast-like synoviocytes are thought to play central roles in the pathogenesis of RA. They have shared and distinct features defining RA pathology. However, these features have not been systematically explored. Using global gene expression profiling, we identified molecular signature and biological network models underlying the pathologic features of macrophage-like vs. fibroblast-like synoviocytes. Based on the network models, we selected key regulators, including POSTN and TWIST1, responsible for synoviocyte migration/invasion causing joint destruction, and their validity was experimentally confirmed. Our findings provide a comprehensive and systematic basis for mechanisms explaining RA pathogenesis and also for identification of therapeutic targets for RA.
NOTCH1–RBPJ complexes drive target gene expression through dynamic interactions with superenhancers
Authors: Wang Hongfang , Zang Chongzhi , Taing Len , Arnett Kelly L. , Wong Yinling Joey , Pear Warren S. , Blacklow Stephen C. , Liu X. Shirley , Aster Jon C. 
Published: December 2013

Significance
Studies focused on understanding how transcription factors control gene expression have shown that transcription-factor binding sites generally greatly exceed the number of regulated genes, making it challenging to identify functional binding sites. Using Notch pathway inhibitors, we identified a subset of Notch-binding sites in leukemia cell genomes that are dynamic, changing in occupancy relatively rapidly when Notch signaling is perturbed. Dynamic Notch sites are highly associated with genes that are directly regulated by Notch and mainly lie in large regulatory switches termed superenhancers, which control genes with key roles in development and cancer. This work links Notch signaling to superenhancers and suggests that assessment of transcription factor–genome dynamics can help to identify functionally important regulatory sites.
Roles of common subunits within distinct multisubunit complexes
Authors: Nakabayashi Yu , Kawashima Satoshi , Enomoto Takemi , Seki Masayuki , Horikoshi Masami 
Published: December 2013

Significance
The same protein is often a subunit of more than one multisubunit protein complex, each of which has a distinct function within cells. Mutating such a protein would cause multiple cellular defects; therefore, it is difficult to distinguish between the function of a protein in one complex from its functions in other complexes. Here, we developed a unique strategy to overcome this problem, which will help to analyze a variety of biological processes by revealing the specific roles played by such proteins within multisubunit protein complexes.
Observation time scale, free-energy landscapes, and molecular symmetry
Authors: Wales David J. , Salamon Peter 
Published: December 2013

SignificanceThis work explains how the experimental time scale determines our perception of the free-energy landscape for a molecular system. Greater temporal resolution naturally resolves more free-energy minima, although this structure may be averaged out over longer time scales. Hence shorter observation times may resolve more states, but result in broken ergodicity. A consistent treatment of the thermodynamics that corresponds with a given experiment must therefore account for the feasibility of different rearrangement mechanisms on the relevant observation time scale. Hence we establish a connection between the concepts of molecular symmetry, ergodicity, and local equilibrium.
Redirecting splicing with bifunctional oligonucleotides
Authors: Brosseau Jean-Philippe , Lucier Jean-François , Lamarche Andrée-Anne , Shkreta Lulzim , Gendron Daniel , Lapointe Elvy , Thibault Philippe , Paquet Éric , Perreault Jean-Pierre , Abou Elela Sherif , Chabot Benoit 
Published: December 2013

Abstract
Ectopic modulators of alternative splicing are important tools to study the function of splice variants and for correcting mis-splicing events that cause human diseases. Such modulators can be bifunctional oligonucleotides made of an antisense portion that determines target specificity, and a non-hybridizing tail that recruits proteins or RNA/protein complexes that affect splice site selection (TOSS and TOES, respectively, for targeted oligonucleotide silencer of splicing and targeted oligonucleotide enhancer of splicing). The use of TOSS and TOES has been restricted to a handful of targets. To generalize the applicability and demonstrate the robustness of TOSS, we have tested this approach on more than 50 alternative splicing events. Moreover, we have developed an algorithm that can design active TOSS with a success rate of 80%. To produce bifunctional oligonucleotides capable of stimulating splicing, we built on the observation that binding sites for TDP-43 can stimulate splicing and improve U1 snRNP binding when inserted downstream from 5′ splice sites. A TOES designed to recruit TDP-43 improved exon 7 inclusion in SMN2. Overall, our study shows that bifunctional oligonucleotides can redirect splicing on a variety of genes, justifying their inclusion in the molecular arsenal that aims to alter the production of splice variants.
c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs
Authors: Gustems Montse , Woellmer Anne , Rothbauer Ulrich , Eck Sebastian H. , Wieland Thomas , Lutter Dominik , Hammerschmidt Wolfgang 
Published: December 2013

Abstract
CpG methylation in mammalian DNA is known to interfere with gene expression by inhibiting the binding of transactivators to their cognate sequence motifs or recruiting proteins involved in gene repression. An Epstein–Barr virus-encoded transcription factor, Zta, was the first example of a sequence-specific transcription factor that preferentially recognizes and selectively binds DNA sequence motifs with methylated CpG residues, reverses epigenetic silencing and activates gene transcription. The DNA binding domain of Zta is homologous to c-Fos, a member of the cellular AP-1 (activator protein 1) transcription factor family, which regulates cell proliferation and survival, apoptosis, transformation and oncogenesis. We have identified a novel AP-1 binding site termed meAP-1, which contains a CpG dinucleotide. If methylated, meAP-1 sites are preferentially bound by the AP-1 heterodimer c-Jun/c-Fos in vitro and in cellular chromatin in vivo. In activated human primary B cells, c-Jun/c-Fos locates to these methylated elements in promoter regions of transcriptionally activated genes. Reminiscent of the viral Zta protein, c-Jun/c-Fos is the first identified cellular member of the AP-1 family of transactivators that can induce expression of genes with methylated, hence repressed promoters, reversing epigenetic silencing.
Targeting and tracing of specific DNA sequences with dTALEs in living cells
Authors: Thanisch Katharina , Schneider Katrin , Morbitzer Robert , Solovei Irina , Lahaye Thomas , Bultmann Sebastian , Leonhardt Heinrich 
Published: December 2013

Abstract
Epigenetic regulation of gene expression involves, besides DNA and histone modifications, the relative positioning of DNA sequences within the nucleus. To trace specific DNA sequences in living cells, we used programmable sequence-specific DNA binding of designer transcription activator-like effectors (dTALEs). We designed a recombinant dTALE (msTALE) with variable repeat domains to specifically bind a 19-bp target sequence of major satellite DNA. The msTALE was fused with green fluorescent protein (GFP) and stably expressed in mouse embryonic stem cells. Hybridization with a major satellite probe (3D-fluorescent in situ hybridization) and co-staining for known cellular structures confirmed in vivo binding of the GFP-msTALE to major satellite DNA present at nuclear chromocenters. Dual tracing of major satellite DNA and the replication machinery throughout S-phase showed co-localization during mid to late S-phase, directly demonstrating the late replication timing of major satellite DNA. Fluorescence bleaching experiments indicated a relatively stable but still dynamic binding, with mean residence times in the range of minutes. Fluorescently labeled dTALEs open new perspectives to target and trace DNA sequences and to monitor dynamic changes in subnuclear positioning as well as interactions with functional nuclear structures during cell cycle progression and cellular differentiation.