bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa
Authors: Ezquerra-Inchausti Maitane , Barandika Olatz , Anasagasti Ander , Irigoyen Cristina , López de Munain Adolfo , Ruiz-Ederra Javier 
Published: January 2017

AbstractRetinitis pigmentosa is the most frequent group of inherited retinal dystrophies. It is highly heterogeneous, with more than 80 disease-causing genes 27 of which are known to cause autosomal dominant RP (adRP), having been identified. In this study a total of 29 index cases were ascertained based on a family tree compatible with adRP. A custom panel of 31 adRP genes was analysed by targeted next-generation sequencing using the Ion PGM platform in combination with Sanger sequencing. This allowed us to detect putative disease-causing mutations in 14 out of the 29 (48.28%) families analysed. Remarkably, around 38% of all adRP cases analysed showed mutations affecting the splicing process, mainly due to mutations in genes coding for spliceosome factors (SNRNP200 and PRPF8) but also due to splice-site mutations in RHO. Twelve of the 14 mutations found had been reported previously and two were novel mutations found in PRPF8 in two unrelated patients. In conclusion, our results will lead to more accurate genetic counselling and will contribute to a better characterisation of the disease. In addition, they may have a therapeutic impact in the future given the large number of studies currently underway based on targeted RNA splicing for therapeutic purposes.
The Molecular Structure of Human Red Blood Cell Membranes from Highly Oriented, Solid Supported Multi-Lamellar Membranes
Authors: Himbert Sebastian , Alsop Richard J. , Rose Markus , Hertz Laura , Dhaliwal Alexander , Moran-Mirabal Jose M. , Verschoor Chris P. , Bowdish Dawn M. E. , Kaestner Lars , Wagner Christian , Rheinstädter Maikel C. 
Published: January 2017

AbstractWe prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (lo) and liquid disordered (ld) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the lo domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains.
Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor
Authors: Flinspach M. , Xu Q. , Piekarz A. D. , Fellows R. , Hagan R. , Gibbs A. , Liu Y. , Neff R. A. , Freedman J. , Eckert W. A. , Zhou M. , Bonesteel R. , Pennington M. W. , Eddinger K. A. , Yaksh T. L. , Hunter M. , Swanson R. V. , Wickenden A. D. 
Published: January 2017

AbstractPain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1.7 blocking peptide. Here we show that JNJ63955918 induces a pharmacological insensitivity to pain that closely recapitulates key features of the Nav1.7-null phenotype seen in mice and humans. Our findings demonstrate that a high degree of selectivity, coupled with a closed-state dependent mechanism of action is required for strong efficacy and indicate that peptides such as JNJ63955918 and other suitably optimized Nav1.7 inhibitors may represent viable non-opioid alternatives for the pharmacological treatment of severe pain.
Evidence for a missing source of efficient ice nuclei
Authors: Du Rui , Du Pengrui , Lu Zedong , Ren Weishan , Liang Zongmin , Qin Saisai , Li Ziming , Wang Yaling , Fu Pingqing 
Published: January 2017

AbstractIt has been known for several decades that some bioaerosols, such as ice-nucleation-active (INA) bacteria, especially Pseudomonas syringae strains, may play a critical potential role in the formation of clouds and precipitation. We investigated bacterial and fungal ice nuclei (IN) in rainwater samples collected from the Hulunber temperate grasslands in North China. The median freezing temperatures (T50) for three years’ worth of unprocessed rain samples were greater than −10 °C based on immersion freezing testing. The heat and filtration treatments inactivated 7–54% and 2–89%, respectively, of the IN activity at temperatures warmer than −10 °C. We also determined the composition of the microbial community. The majority of observed Pseudomonas strains were distantly related to the verified ice-nucleating Pseudomonas strains, as revealed by phylogenetic analysis. Here, we show that there are submicron INA particles <220 nm in rainwater that are not identifiable as the known species of high-INA bacteria and fungi and there may be a new potential type of efficient submicroscale or nanoscale ice nucleator in the regional rainwater samplers. Our results suggest the need for a reinterpretation of the source of high-INA material in the formation of precipitation and contribute to the search for new methods of weather modification.
Polarized white light from hybrid organic/III-nitrides grating structures
Authors: Athanasiou M. , Smith R. M. , Ghataora S. , Wang T. 
Published: January 2017

AbstractHighly polarised white light emission from a hybrid organic/inorganic device has been achieved. The hybrid devices are fabricated by means of combining blue InGaN-based multiple quantum wells (MQWs) with a one-dimensional (1D) grating structure and down-conversion F8BT yellow light emitting polymer. The 1D grating structure converts the blue emission from unpolarised to highly polarised; Highly polarised yellow emission has been achieved from the F8BT polymer filled and aligned along the periodic nano-channels of the grating structure as a result of enhanced nano-confinement. Optical polarization measurements show that our device demonstrates a polarization degree of up to 43% for the smallest nano-channel width. Furthermore, the hybrid device with such a grating structure allows us to achieve an optimum relative orientation between the dipoles in the donor (i.e., InGaN/GaN MQWs) and the diploes in the acceptor (i.e., the F8BT), maximizing the efficiency of non-radiative energy transfer (NRET) between the donor and the acceptor. Time–resolved micro photoluminescence measurements show a 2.5 times enhancement in the NRET efficiency, giving a maximal NRET efficiency of 90%. It is worth highlighting that the approach developed paves the way for the fabrication of highly polarized white light emitters.
Dendritic and Axonal Propagation Delays Determine Emergent Structures of Neuronal Networks with Plastic Synapses
Authors: Madadi Asl Mojtaba , Valizadeh Alireza , Tass Peter A. 
Published: January 2017

AbstractSpike-timing-dependent plasticity (STDP) modifies synaptic strengths based on the relative timing of pre- and postsynaptic spikes. The temporal order of spikes turned out to be crucial. We here take into account how propagation delays, composed of dendritic and axonal delay times, may affect the temporal order of spikes. In a minimal setting, characterized by neglecting dendritic and axonal propagation delays, STDP eliminates bidirectional connections between two coupled neurons and turns them into unidirectional connections. In this paper, however, we show that depending on the dendritic and axonal propagation delays, the temporal order of spikes at the synapses can be different from those in the cell bodies and, consequently, qualitatively different connectivity patterns emerge. In particular, we show that for a system of two coupled oscillatory neurons, bidirectional synapses can be preserved and potentiated. Intriguingly, this finding also translates to large networks of type-II phase oscillators and, hence, crucially impacts on the overall hierarchical connectivity patterns of oscillatory neuronal networks.
miRsig: a consensus-based network inference methodology to identify pan-cancer miRNA-miRNA interaction signatures
Authors: Nalluri Joseph J. , Barh Debmalya , Azevedo Vasco , Ghosh Preetam 
Published: January 2017

AbstractDecoding the patterns of miRNA regulation in diseases are important to properly realize its potential in diagnostic, prog- nostic, and therapeutic applications. Only a handful of studies computationally predict possible miRNA-miRNA interactions; hence, such interactions require a thorough investigation to understand their role in disease progression. In this paper, we design a novel computational pipeline to predict the common signature/core sets of miRNA-miRNA interactions for different diseases using network inference algorithms on the miRNA-disease expression profiles; the individual predictions of these algorithms were then merged using a consensus-based approach to predict miRNA-miRNA associations. We next selected the miRNA-miRNA associations across particular diseases to generate the corresponding disease-specific miRNA-interaction networks. Next, graph intersection analysis was performed on these networks for multiple diseases to identify the common signature/core sets of miRNA interactions. We applied this pipeline to identify the common signature of miRNA-miRNA inter- actions for cancers. The identified signatures when validated using a manual literature search from PubMed Central and the PhenomiR database, show strong relevance with the respective cancers, providing an indirect proof of the high accuracy of our methodology. We developed miRsig, an online tool for analysis and visualization of the disease-specific signature/core miRNA-miRNA interactions, available at: http://bnet.egr.vcu.edu/miRsig.
PDLIM5 links kidney anion exchanger 1 (kAE1) to ILK and is required for membrane targeting of kAE1
Authors: Su Ya , Hiemstra Thomas F. , Yan Yahui , Li Juan , Karet Hannah I. , Rosen Lawrence , Moreno Pablo , Karet Frankl Fiona E. 
Published: January 2017

AbstractAnion exchanger 1 (AE1) mediates Cl−/HCO3− exchange in erythrocytes and kidney intercalated cells where it functions to maintain normal bodily acid-base homeostasis. AE1’s C-terminal tail (AE1C) contains multiple potential membrane targeting/retention determinants, including a predicted PDZ binding motif, which are critical for its normal membrane residency. Here we identify PDLIM5 as a direct binding partner for AE1 in human kidney, via PDLIM5’s PDZ domain and the PDZ binding motif in AE1C. Kidney AE1 (kAE1), PDLIM5 and integrin-linked kinase (ILK) form a multiprotein complex in which PDLIM5 provides a bridge between ILK and AE1C. Depletion of PDLIM5 resulted in significant reduction in kAE1 at the cell membrane, whereas over-expression of kAE1 was accompanied by increased PDLIM5 levels, underscoring the functional importance of PDLIM5 for proper kAE1 membrane residency, as a crucial linker between kAE1 and actin cytoskeleton-associated proteins in polarized cells.
Nutrition affects insect susceptibility to Bt toxins
Authors: Deans Carrie A. , Behmer Spencer T. , Tessnow Ashley E. , Tamez-Guerra Patricia , Pusztai-Carey Marianne , Sword Gregory A. 
Published: January 2017

AbstractPesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.
Low-temperature atomic layer epitaxy of AlN ultrathin films by layer-by-layer, in-situ atomic layer annealing
Authors: Shih Huan-Yu , Lee Wei-Hao , Kao Wei-Chung , Chuang Yung-Chuan , Lin Ray-Ming , Lin Hsin-Chih , Shiojiri Makoto , Chen Miin-Jang 
Published: January 2017

AbstractLow-temperature epitaxial growth of AlN ultrathin films was realized by atomic layer deposition (ALD) together with the layer-by-layer, in-situ atomic layer annealing (ALA), instead of a high growth temperature which is needed in conventional epitaxial growth techniques. By applying the ALA with the Ar plasma treatment in each ALD cycle, the AlN thin film was converted dramatically from the amorphous phase to a single-crystalline epitaxial layer, at a low deposition temperature of 300 °C. The energy transferred from plasma not only provides the crystallization energy but also enhances the migration of adatoms and the removal of ligands, which significantly improve the crystallinity of the epitaxial layer. The X-ray diffraction reveals that the full width at half-maximum of the AlN (0002) rocking curve is only 144 arcsec in the AlN ultrathin epilayer with a thickness of only a few tens of nm. The high-resolution transmission electron microscopy also indicates the high-quality single-crystal hexagonal phase of the AlN epitaxial layer on the sapphire substrate. The result opens a window for further extension of the ALD applications from amorphous thin films to the high-quality low-temperature atomic layer epitaxy, which can be exploited in a variety of fields and applications in the near future.
Population genetics of the Manila clam (Ruditapes philippinarum) introduced in North America and Europe
Authors: Cordero David , Delgado Marina , Liu Baozhong , Ruesink Jennifer , Saavedra Carlos 
Published: January 2017

AbstractGlobally, the Manila clam (Ruditapes philippinarum) stands as the second most important bivalve species in fisheries and aquaculture. Native to the Pacific coast of Asia, it is now well-established in North America and Europe, where its on-going management reflects local economic interests. The historic record of transfers spans the 20th century and suggests sequential movement from Japan to North America, as a hitch-hiker on oysters, and then intentional introduction in Europe, but global genetic data are missing. We have studied mitochondrial DNA and microsatellite markers in nine populations from Asia, North America and Europe. The results from the two types of markers indicated a good concordance of present-day genetic structure with the reported history of clam transfers across continents, and no evidence of relevant concealed introductions from continental Asia in Europe and North America. However, European populations showed a loss of genetic variability and significant genetic differentiation as compared to their American counterparts. Our study shows that in spite of the increasing ease for species to spread out of their native range, in the case of the Manila clam this has not resulted in new invasion waves in the two studied continents.
Comparative genome analyses of Mycobacterium avium reveal genomic features of its subspecies and strains that cause progression of pulmonary disease
Authors: Uchiya Kei-ichi , Tomida Shuta , Nakagawa Taku , Asahi Shoki , Nikai Toshiaki , Ogawa Kenji 
Published: January 2017

AbstractPulmonary disease caused by nontuberculous mycobacteria (NTM) is increasing worldwide.Mycobacterium aviumis the most clinically significant NTM species in humans and animals, and comprises four subspecies:M. aviumsubsp.avium(MAA),M. aviumsubsp.silvaticum(MAS),M. aviumsubsp.paratuberculosis(MAP), andM. aviumsubsp.hominissuis(MAH). To improve our understanding of the genetic landscape and diversity ofM. aviumand its role in disease, we performed a comparative genome analysis of 79 M. aviumstrains. Our analysis demonstrated that MAH is an open pan-genome species. Phylogenetic analysis based on single nucleotide variants showed that MAH had the highest degree of sequence variability among the subspecies, and MAH strains isolated in Japan and those isolated abroad possessed distinct phylogenetic features. Furthermore, MAP strains, MAS and MAA strains isolated from birds, and many MAH strains that cause the progression of pulmonary disease were grouped in each specific cluster. Comparative genome analysis revealed the presence of genetic elements specific to each lineage, which are thought to be acquired via horizontal gene transfer during the evolutionary process, and identified potential genetic determinants accounting for the pathogenic and host range characteristics ofM. avium.
Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling
Authors: Kumar Prabhakaran , Alharshawi Khaled , Bhattacharya Palash , Marinelarena Alejandra , Haddad Christine , Sun Zuoming , Chiba Shigeru , Epstein Alan L. , Prabhakar Bellur S. 
Published: January 2017

AbstractRegulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired. We report a novel TCR-independent strategy for the selective proliferation of Foxp3+Tregs (without Teff proliferation), by co-culturing CD4+ T-cells with OX40 L+Jagged(JAG)-1+ bone marrow-derived DCs differentiated with GM-CSF or treating them with soluble OX40 L and JAG1 in the presence of exogenous IL-2. Tregs expanded using soluble OX40 L and JAG1 were of suppressive phenotype and delayed the onset of diabetes in NOD mice. Ligation of OX40 L and JAG1 with their cognate-receptors OX40 and Notch3, preferentially expressed on Tregs but not on Teff cells, was required for selective Treg proliferation. Soluble OX40L-JAG1-induced NF-κB activation as well as IL-2-induced STAT5 activation were essential for the proliferation of Tregs with sustained Foxp3 expression. Altogether, these findings demonstrate the utility of soluble OX40 L and JAG1 to induce TCR-independent Treg proliferation.
Personalised proteome analysis by means of protein microarrays made from individual patient samples
Authors: Syafrizayanti  , Lueong Smiths S. , Di Cuixia , Schaefer Jonas V. , Plückthun Andreas , Hoheisel Jörg D. 
Published: January 2017

AbstractDNA sequencing has advanced to a state that permits studying the genomes of individual patients as nearly a matter of routine. Towards analysing a tissue’s protein content in a similar manner, we established a method for the production of microarrays that represent full-length proteins as they are encoded in individual specimens, exhibiting the particular variations, such as mutations or splice variations, present in these samples. From total RNA isolates, each transcript is copied to a specific location on the array by an on-chip polymerase elongation reaction, followed by in situ cell-free transcription and translation. These microarrays permit parallel analyses of variations in protein structure and interaction that are specific to particular samples.
Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies
Authors: Mouka Aurélie , Izard Vincent , Tachdjian Gérard , Brisset Sophie , Yates Frank , Mayeur Anne , Drévillon Loïc , Jarray Rafika , Leboulch Philippe , Maouche-Chrétien Leila , Tosca Lucie 
Published: January 2017

AbstractDespite progress in human reproductive biology, the cause of male infertility often remains unknown, due to the lack of appropriate and convenient in vitro models of meiosis. Induced pluripotent stem cells (iPSCs) derived from the cells of infertile patients could provide a gold standard model for generating primordial germ cells and studying their development and the process of spermatogenesis. We report the characterization of a complex chromosomal rearrangement (CCR) in an azoospermic patient, and the successful generation of specific-iPSCs from PBMC-derived erythroblasts. The CCR was characterized by karyotype, fluorescence in situ hybridization and oligonucleotide-based array-comparative genomic hybridization. The CCR included five breakpoints and was caused by the inverted insertion of a chromosome 12 segment into the short arm of one chromosome 7 and a pericentric inversion of the structurally rearranged chromosome 12. Gene mapping of the breakpoints led to the identification of a candidate gene, SYCP3. Erythroblasts from the patient were reprogrammed with Sendai virus vectors to generate iPSCs. We assessed iPSC pluripotency by RT-PCR, immunofluorescence staining and teratoma induction. The generation of specific-iPSCs from patients with a CCR provides a valuable in vitro genetic model for studying the mechanisms by which chromosomal abnormalities alter meiosis and germ cell development.
Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx
Authors: Zhang Yang , Sturgis Erich M. , Li Yuncheng , Wei Qingyi , Huang Zhigang , Li Guojun 
Published: January 2017

AbstractFunctional mouse double minute-2 (MDM2) promoter variants may alter MDM2 expression and thus affect radiotherapy response and prognosis of squamous cell carcinoma of oropharynx (SCCOP). Thus we assessed association of 2 functional MDM2 promoter variants with recurrence risk of SCCOP. The disease-free survival (DFS) of patients with MDM2rs2279744 TT or MDM2rs937283 AA genotypes was significantly reduced compared with that of patients with corresponding GT/GG or AG/GG genotypes. Multivariable analysis showed patients with TT or AA genotypes had a significantly higher risk of SCCOP recurrence than those with corresponding GT/GG or AG/GG genotypes did. Furthermore, patients with combined risk genotypes of the 2 polymorphisms had significantly worse DFS and a higher recurrence risk than patients with fewer combined risk genotypes did (Ptrend < 0.001). Compared with patients with 0 risk genotypes, patients with 1 or 2 risk genotypes had an approximately 3- or 11-fold increased risk of SCCOP recurrence, respectively. Notably, for both individual and combined polymorphisms, the above similar recurrence risks were particularly higher among patients with human papilloma virus (HPV)-positive tumors. Taken together, our findings suggest that MDM2 promoter variants individually, or more likely jointly, play a role in determining the risk of recurrence of SCCOP, particularly HPV-positive SCCOP.