bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial statistical modelling of capillary non-perfusion in the retina
Authors: MacCormick Ian J. C. , Zheng Yalin , Czanner Silvester , Zhao Yitian , Diggle Peter J. , Harding Simon P. , Czanner Gabriela 
Published: November 2017

AbstractManual grading of lesions in retinal images is relevant to clinical management and clinical trials, but it is time-consuming and expensive. Furthermore, it collects only limited information - such as lesion size or frequency. The spatial distribution of lesions is ignored, even though it may contribute to the overall clinical assessment of disease severity, and correspond to microvascular and physiological topography. Capillary non-perfusion (CNP) lesions are central to the pathogenesis of major causes of vision loss. Here we propose a novel method to analyse CNP using spatial statistical modelling. This quantifies the percentage of CNP-pixels in each of 48 sectors and then characterises the spatial distribution with goniometric functions. We applied our spatial approach to a set of images from patients with malarial retinopathy, and found it compares favourably with the raw percentage of CNP-pixels and also with manual grading. Furthermore, we were able to quantify a biological characteristic of macular CNP in malaria that had previously only been described subjectively: clustering at the temporal raphe. Microvascular location is likely to be biologically relevant to many diseases, and so our spatial approach may be applicable to a diverse range of pathological features in the retina and other organs.
Pathologic N0 Status in Clinical T1N0M0 Lung Adenocarcinoma is Predictable by the Solid Component Proportion with Quantitative CT Number Analysis
Authors: Li Meng , Wu Ning , Zhang Li , Sun Wei , Wang Jianwei , Lv Lv , Ren Jiansong , Lin Dongmei 
Published: November 2017

AbstractCorrectly predicting pathologic regional node-negative (pN0) disease in patients with lung cancer before operation may avoid unnecessary mediastinal lymph node dissection (MLND). In this study, we analyze the value of the radiographic and histopathological features of primary tumors for predicting pN0 status in cT1N0M0 lung adenocarcinoma and to establish an optimal surgical strategy for avoiding MLND in cT1N0M0 lung adenocarcinoma patients. We retrospectively investigated the histopathological and radiographic data of 348 surgically resected cT1N0M0 lung adenocarcinoma patients with systematic lymph node dissection from January 2005 to December 2012. Histopathological features and radiographic features were analyzed. Multivariable analysis was used to identify significant predictors of pN0 disease. Our results showed that pN0 disease was detected in 306 patients (87.9%) among the 348 patients with cT1N0M0 lung adenocarcinoma. A decreasing trend of the pN0 disease proportion was observed with both increasing histological grade and decreased differentiation (P < 0.001). In multivariable analysis, the solid component proportion was a significant predictor of pN0 disease. Among 110 patients with a solid component proportion of no more than 21.3%, mediastinal lymph node involvement was not observed. Patients who meet this criterion may be successfully managed with lung resection without MLND.
A hybrid strain and thermal energy harvester based on an infra-red sensitive Er3+ modified poly(vinylidene fluoride) ferroelectret structure
Authors: Ghosh Sujoy Kumar , Xie Mengying , Bowen Christopher Rhys , Davies Philip R. , Morgan David J. , Mandal Dipankar 
Published: November 2017

AbstractIn this paper, a novel infra-red (IR) sensitive Er3+ modified poly(vinylidene fluoride) (PVDF) (Er-PVDF) film is developed for converting both mechanical and thermal energies into useful electrical power. The addition of Er3+ to PVDF is shown to improve piezoelectric properties due to the formation of a self-polarized ferroelectric β-phase and the creation of an electret-like porous structure. In addition, we demonstrate that Er3+ acts to enhance heat transfer into the Er-PVDF film due to its excellent infrared absorbance, which, leads to rapid and large temperature fluctuations and improved pyroelectric energy transformation. We demonstrate the potential of this novel material for mechanical energy harvesting by creating a durable ferroelectret energy harvester/nanogenerator (FTNG). The high thermal stability of the β-phase enables the FTNG to harvest large temperature fluctuations (ΔT ~ 24 K). Moreover, the superior mechanosensitivity, SM ~ 3.4 VPa−1 of the FTNG enables the design of a wearable self-powered health-care monitoring system by human-machine integration. The combination of rare-earth ion, Er3+ with the ferroelectricity of PVDF provides a new and robust approach for delivering smart materials and structures for self-powered wireless technologies, sensors and Internet of Things (IoT) devices.
An engineered opsin monomer scrambles phospholipids
Authors: Pandey Kalpana , Ploier Birgit , Goren Michael A. , Levitz Joshua , Khelashvili George , Menon Anant K. 
Published: November 2017

AbstractThe G protein-coupled receptor opsin is a phospholipid scramblase that facilitates rapid transbilayer phospholipid exchange in liposomes. The mechanism by which opsin scrambles lipids is unknown. It has been proposed that lipid translocation may occur at protein-protein interfaces of opsin dimers. To test this possibility, we rationally engineered QUAD opsin by tryptophan substitution of four lipid-facing residues in transmembrane helix 4 (TM4) that is known to be important for dimerization. Atomistic molecular dynamics simulations of wild type and QUAD opsins combined with continuum modeling revealed that the tryptophan substitutions lower the energetically unfavorable residual hydrophobic mismatch between TM4 and the membrane, reducing the drive of QUAD opsin to dimerize. We purified thermostable wild type and QUAD opsins, with or without a SNAP tag for fluorescence labeling. Single molecule fluorescence measurements of purified SNAP-tagged constructs revealed that both proteins are monomers. Fluorescence-based activity assays indicated that QUAD opsin is a fully functional scramblase. However, unlike wild type opsin which dimerizes en route to insertion into phospholipid vesicles, QUAD opsin reconstitutes as a monomer. We conclude that an engineered opsin monomer can scramble phospholipids, and that the lipid-exposed face of TM4 is unlikely to contribute to transbilayer phospholipid exchange.
Adrenergic receptor agonists induce the differentiation of pluripotent stem cell-derived hepatoblasts into hepatocyte-like cells
Authors: Kotaka Maki , Toyoda Taro , Yasuda Katsutaro , Kitano Yuko , Okada Chihiro , Ohta Akira , Watanabe Akira , Uesugi Motonari , Osafune Kenji 
Published: November 2017

AbstractCurrent induction methods of hepatocytes from human induced pluripotent stem cells (hiPSCs) are neither low cost nor stable. By screening a chemical library of 1,120 bioactive compounds and known drugs, we identified the α1-adrenergic receptor agonist methoxamine hydrochloride as a small molecule that promotes the differentiation of hiPSC-derived hepatoblasts into ALBUMIN+ hepatocyte-like cells. Other α1-adrenergic receptor agonists also induced the differentiation of hepatocyte-like cells, and an α1-receptor antagonist blocked the hepatic-inducing activity of methoxamine hydrochloride and that of the combination of hepatocyte growth factor (HGF) and Oncostatin M (OsM), two growth factors often used for the induction of hepatoblasts into hepatocyte-like cells. We also confirmed that treatment with methoxamine hydrochloride activates the signal transducer and activator of transcription 3 (STAT3) pathway downstream of IL-6 family cytokines including OsM. These findings allowed us to establish hepatic differentiation protocols for both mouse embryonic stem cells (mESCs) and hiPSCs using small molecules at the step from hepatoblasts into hepatocyte-like cells. The results of the present study suggest that α1-adrenergic agonists induce hepatocyte-like cells by working downstream of HGF and OsM to activate STAT3.
Toehold-enhanced LNA probes for selective pull down and single-molecule analysis of native chromatin
Authors: Hermans Nicolaas , Huisman Juriën Jori , Brouwer Thomas Bauke , Schächner Christopher , van Heusden G. Paul H. , Griesenbeck Joachim , van Noort John 
Published: November 2017

AbstractThe organization of DNA into chromatin is thought to regulate gene expression in eukaryotes. To study its structure in vitro, there is a need for techniques that can isolate specific chromosomal loci of natively assembled chromatin. Current purification methods often involve chemical cross-linking to preserve the chromatin composition. However, such cross-linking may affect the native structure. It also impedes single molecule force spectroscopy experiments, which have been instrumental to probe chromatin folding. Here we present a method for the incorporation of affinity tags, such as biotin, into native nucleoprotein fragments based on their DNA sequence, and subsequent single molecule analysis by magnetic tweezers. DNA oligos with several Locked Nucleic Acid (LNA) nucleotides are shown to selectively bind to target DNA at room temperature, mediated by a toehold end in the target, allowing for selective purification of DNA fragments. The stability of the probe-target hybrid is sufficient to withstand over 65 pN of force. We employ these probes to obtain force-extension curves of native chromatin fragments of the 18S ribosomal DNA from the yeast Saccharomyces cerevisiae. These experiments yield valuable insights in the heterogeneity in structure and composition of natively assembled chromatin at the single-molecule level.
A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice
Authors: Kashiwagi Kenji , Ito Sadahiro , Maeda Shuichiro , Kato Goro 
Published: November 2017

AbstractSrc knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole retinas was significantly lower than that in young SD/SD mice in the absence of inflammation and elevated intraocular pressure, resembling the pathogenesis of progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice exhibited no age-related RGC loss. The age-related retinal RGC number reduction was greater in the peripheral rather than the mid-peripheral region of the retina in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of ageing SD/SD mice was significantly higher than that in young SD/SD mice. These results suggest that Src regulates RGC survival during ageing in a manner that depends on Ser75 phosphorylation.
Induction of auxin biosynthesis and WOX5 repression mediate changes in root development in Arabidopsis exposed to chitosan
Authors: Lopez-Moya Federico , Escudero Nuria , Zavala-Gonzalez Ernesto A. , Esteve-Bruna David , Blázquez Miguel A. , Alabadí David , Lopez-Llorca Luis V. 
Published: November 2017

AbstractChitosan is a natural polymer with applications in agriculture, which causes plasma membrane permeabilisation and induction of intracellular reactive oxygen species (ROS) in plants. Chitosan has been mostly applied in the phylloplane to control plant diseases and to enhance plant defences, but has also been considered for controlling root pests. However, the effect of chitosan on roots is virtually unknown. In this work, we show that chitosan interfered with auxin homeostasis in Arabidopsis roots, promoting a 2–3 fold accumulation of indole acetic acid (IAA). We observed chitosan dose-dependent alterations of auxin synthesis, transport and signalling in Arabidopsis roots. As a consequence, high doses of chitosan reduce WOX5 expression in the root apical meristem and arrest root growth. Chitosan also propitiates accumulation of salicylic (SA) and jasmonic (JA) acids in Arabidopsis roots by induction of genes involved in their biosynthesis and signalling. In addition, high-dose chitosan irrigation of tomato and barley plants also arrests root development. Tomato root apices treated with chitosan showed isodiametric cells respect to rectangular cells in the controls. We found that chitosan causes strong alterations in root cell morphology. Our results highlight the importance of considering chitosan dose during agronomical applications to the rhizosphere.
Novel halos in light kaonic nuclei as an indicator of nuclear equation of state at supra-normal densities
Authors: Yang Rong-Yao , Jiang Wei-Zhou , Wei Si-Na , Zhang Dong-Rui 
Published: November 2017

AbstractThe sensitive correlations between the low-density halo structure and the high-density properties of the nuclear equation of state (EOS) are constructed in light kaonic nuclei with the relativistic mean-field theory. More specifically, the 1p1/2 halo spreads out linearly with increasing the pressure and sound velocity square at supra-normal densities and decreasing the incompressibility at saturation density. These results suggest that the novel halo in light kaonic nuclei can serve as a sensitive indicator of the nuclear EOS of symmetric matter at supra-normal densities. The experimental production and detection of the light kaonic nuclei, yet to be available, is discussed in some details at last.
Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype
Authors: Albers Andreas E. , Qian Xu , Kaufmann Andreas M. , Coordes Annekatrin 
Published: November 2017

AbstractConsistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV−/p16−, 6.7% for HPV−/p16+ and 7.3% for HPV+/P16−. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV−/p16+ HNSCC was intermediate while HPV+/p16− and HPV−/p16− had the shortest survival outcomes. The clearly distinct survival of HPV−/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.
MALE STERILE6021 (MS6021) is required for the development of anther cuticle and pollen exine in maize
Authors: Tian Youhui , Xiao Senlin , Liu Juan , Somaratne Yamuna , Zhang Hua , Wang Mingming , Zhang Huairen , Zhao Li , Chen Huabang 
Published: November 2017

AbstractThe anther cuticle and pollen wall function as physical barriers that protect genetic material from various environmental stresses. The anther cuticle is composed of wax and cutin, the pollen wall includes exine and intine, and the components of the outer exine are collectively called sporopollenin. Other than cuticle wax, cutin and sporopollenin are biopolymers compounds. The precise constituents and developmental mechanism of these biopolymeric are poorly understood. Here, we reported a complete male sterile mutant, male sterile6021, in maize. The mutant displayed a smooth anther surface and irregular pollen wall formation before anthesis, and its tapetum was degraded immaturely. Gas chromatography-mass spectrometry analysis revealed a severe reduction of lipid derivatives in the mutant anther. We cloned the gene by map based cloning. It encoded a fatty acyl carrier protein reductase that was localized in plastids. Expression analysis indicated that MS6021 was mainly expressed in the tapetum and microspore after the microspore was released from the tetrad. Functional complementation of the orthologous Arabidopsis mutant demonstrated that MS6021 is conserved between monocots and dicots and potentially even in flowering plants. MS6021 plays a conserved, essential role in the successful development of anther cuticle and pollen exine in maize.
A small cassette enables conditional gene inactivation by CRISPR/Cas9
Authors: Guzzardo Paloma M. , Rashkova Christina , dos Santos Rodrigo L. , Tehrani Raha , Collin Philippe , Bürckstümmer Tilmann 
Published: November 2017

AbstractThe availability of CRISPR/Cas9 technology has enabled the rapid establishment of gene knockouts in many cell types and even whole organisms. However, conditional inactivation of essential genes remains a challenge. We devised an approach named DECAI (DEgradation based on Cre-regulated- Artificial Intron). It utilizes a small cassette of just 201 nucleotides that is inserted into the coding exon of a target gene using CRISPR/Cas9 technology and homology-directed repair. As its sequence is derived from an artificial intron, the cassette is removed by the splicing machinery and thus leaves no trace in the “off-state”. Upon activation with Cre recombinase (“on-state”), the intron is crippled and the target gene is disrupted by a series of stop codons. We exemplify the utility of this approach on several non-essential and essential human genes. Clones bearing the conditional knockout cassette are recovered at frequencies above 5% and cassette function can be traced at the genomic DNA and the mRNA level. Importantly, cassette activation leads to loss of gene expression as judged by flow cytometry, Western blot or immunofluorescence. Altogether, this highlights the broad utility of the approach for conditional gene inactivation and suggests that this tool could be used to study the loss-of-function phenotypes of essential genes.
2.8 μm emission and OH quenching analysis in Ho3+ doped fluorotellurite-germanate glasses sensitized by Yb3+ and Er3+
Authors: Zhang Junjie , Lu Yu , Cai Muzhi , Tian Ying , Huang Feifei , Guo Yanyan , Xu Shiqing 
Published: November 2017

AbstractThe use of Yb3+ and Er3+ co-doping with Ho3+ to enhance and broaden the Ho3+: 5I6 → 5I7 ~2.8 μm emissions are investigated in the fluorotellurite-germanate glasses. An intense ~3 μm emission with a full width at half maximum (FWHM) of 245 nm is achieved in the Er3+/Ho3+/Yb3+ triply-doped fluorotellurite-germanate glass upon excitation at 980 nm. The glass not only possesses considerably low OH− absorption coefficient (0.189 cm−1), but also exhibits low phonon energy (704 cm−1). Moreover, the measured lifetime of Ho3+: 5I6 level is as high as 0.218 ms. In addition, the energy transfer rate to hydroxyl groups and quantum efficiency (η) of 5I6 level were calculated in detail by fitting the variations of lifetimes vs. the OH− concentrations. The formation ability and thermal stability of glasses have been improved by introducing GeO2 into fluorotellurite glasses. Results reveal that Er3+/Ho3+/Yb3+ triply-doped fluorotellurite-germanate glass is a potential kind of laser glass for efficient 3 μm laser.
Concurrent structural and biophysical traits link with immunoglobulin light chains amyloid propensity
Authors: Oberti Luca , Rognoni Paola , Barbiroli Alberto , Lavatelli Francesca , Russo Rosaria , Maritan Martina , Palladini Giovanni , Bolognesi Martino , Merlini Giampaolo , Ricagno Stefano 
Published: November 2017

AbstractLight chain amyloidosis (AL), the most common systemic amyloidosis, is caused by the overproduction and the aggregation of monoclonal immunoglobulin light chains (LC) in target organs. Due to genetic rearrangement and somatic hypermutation, virtually, each AL patient presents a different amyloidogenic LC. Because of such complexity, the fine molecular determinants of LC aggregation propensity and proteotoxicity are, to date, unclear; significantly, their decoding requires investigating large sets of cases. Aiming to achieve generalizable observations, we systematically characterised a pool of thirteen sequence-diverse full length LCs. Eight amyloidogenic LCs were selected as responsible for severe cardiac symptoms in patients; five non-amyloidogenic LCs were isolated from patients affected by multiple myeloma. Our comprehensive approach (consisting of spectroscopic techniques, limited proteolysis, and X-ray crystallography) shows that low fold stability and high protein dynamics correlate with amyloidogenic LCs, while hydrophobicity, structural rearrangements and nature of the LC dimeric association interface (as observed in seven crystal structures here presented) do not appear to play a significant role in defining amyloid propensity. Based on the structural and biophysical data, our results highlight shared properties driving LC amyloid propensity, and these data will be instrumental for the design of synthetic inhibitors of LC aggregation.
Blood Serum Calorimetry Indicates the Chemotherapeutic Efficacy in Lung Cancer Treatment
Authors: Kędra-Królik Karolina , Chmielewska Izabela , Michnik Anna , Zarzycki Piotr 
Published: November 2017

AbstractChemotherapy is a primary treatment for the metastatic lung cancer patients. To select the most effective combination of drugs, we need an efficient way of assessing tumor response. Here, we showed that differential scanning calorimetry (DSC) analysis of blood serum proteins could reveal the patient response to the treatment. If chemotherapy is effective, serum proteins DSC curve of non-small cellular lung cancer (NSCLC) case is similar to the those of the healthy individuals. If treatment fails, notable changes occur in the DSC profile of NSCLC patient’s blood serum. Our preliminary work illustrates how thermal analysis of changes in the heat capacity of blood serum proteins can provide an insight into patient response to chemotherapy – the essential information for any successive lung cancer treatment.
Adaptive laboratory evolution of Corynebacterium glutamicum towards higher growth rates on glucose minimal medium
Authors: Pfeifer Eugen , Gätgens Cornelia , Polen Tino , Frunzke Julia 
Published: November 2017

AbstractIn this work, we performed a comparative adaptive laboratory evolution experiment of the important biotechnological platform strain Corynebacterium glutamicum ATCC 13032 and its prophage-free variant MB001 towards improved growth rates on glucose minimal medium. Both strains displayed a comparable adaptation behavior and no significant differences in genomic rearrangements and mutation frequencies. Remarkably, a significant fitness leap by about 20% was observed for both strains already after 100 generations. Isolated top clones (UBw and UBm) showed an about 26% increased growth rate on glucose minimal medium. Genome sequencing of evolved clones and populations resulted in the identification of key mutations in pyk (pyruvate kinase), fruK (1-phosphofructokinase) and corA encoding a Mg2+ importer. The reintegration of selected pyk and fruK mutations resulted in an increased glucose consumption rate and ptsG expression causative for the accelerated growth on glucose minimal medium, whereas corA mutations improved growth under Mg2+ limiting conditions. Overall, this study resulted in the identification of causative key mutations improving the growth of C. glutamicum on glucose. These identified mutational hot spots as well as the two evolved top strains, UBw and UBm, represent promising targets for future metabolic engineering approaches.