bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spatial distribution pattern of Connexin26 expression in supporting cells and its role in outer hair cell survival
Authors: Chen Sen , Xu Kai , Xie Le , Cao Hai-Yan , Wu Xia , Du An-Na , He Zu-Hong , Lin Xi , Sun Yu , Kong Wei-Jia 
Published: December 2018

AbstractMutations in the GJB2 gene (which encodes Connexin26 (Cx26)) account for about a quarter of all cases of non-syndromic deafness. Previous studies have indicated that knockout (KO) of Gjb2 gene during early postnatal days can cause outer hair cell (OHC) loss in mouse models. However, the postnatal spatial distribution pattern of Cx26 in different types of supporting cells (SCs) and the role of such distributions for the survival of OHCs is still obscure. In this study, the spatial distribution patterns of Cx26 in SCs were observed, and based on these observations different spatial Cx26-null mouse models were established in order to determine the effect of changes in the spatial distribution of Cx26 in SCs on the survival of OHCs. At postnatal day (P)3, unlike the synchronous expression of Cx26 along both longitudinal and radial boundaries of most types of SCs, Cx26 expression was primarily observed along the longitudinal boundaries of rows of Deiter’s cells (DCs). From P5 to P7, radial expression of Cx26 was gradually observed between adjacent rows of DCs. When Gjb2 gene was knocked out at random in different types of SCs, about 40% of the total DCs lost Cx26 expression and these Cx26-null DCs were distributed randomly in all three rows of DCs. The mice in this randomly Cx26-null group showed normal hearing and no significant OHC loss. When using a longitudinal KO pattern to induce knockout of Gjb2 gene specifically in the third row of DCs, about 33% of the total DCs lost Cx26 expression in this specific longitudinally Cx26-null group. The mice in this group showed late-onset hearing loss and significant OHC loss, however, the morphology of corresponding DCs was slightly altered. In both experimental groups, no substantial DC loss was observed. These results indicate that longitudinal Cx26-based channels are predominant in DCs during P3–P5. The Cx26 expression along rows of DCs might play a key role in the survival of OHCs, but this longitudinal KO pattern in DCs has a limited effect on DC survival or on its postnatal development.
Tumor treating fields increases membrane permeability in glioblastoma cells
Authors: Chang Edwin , Patel Chirag B. , Pohling Christoph , Young Caroline , Song Jonathan , Flores Thomas Anthony , Zeng Yitian , Joubert Lydia-Marie , Arami Hamed , Natarajan Arutselvan , Sinclair Robert , Gambhir Sanjiv S. 
Published: December 2018

AbstractGlioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24 h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.
Human granulocytes undergo cell death via autophagy
Authors: Kajiume Teruyuki , Kobayashi Masao 
Published: December 2018

AbstractMature neutrophils must be quickly removed from inflammatory sites to prevent tissue damage. Neutrophil removal is thought to be accomplished primarily through caspase-dependent apoptosis, which involves several genes of mitochondrial origin. However, mature neutrophils show reduced gene transcription and mitochondrial numbers. We predicted that neutrophils utilize other cell death mechanisms and investigated programmed cell death in human peripheral blood mononuclear cells (MNCs) and polymorphonuclear cells (PMNCs or neutrophil fractions). Unlike MNCs, PMNCs did not undergo DNA fragmentation and were not TUNEL positive, but expressed LC3-II, an autophagy marker. We also found that during differentiation, autophagy inhibitor 3-MA, and not caspase inhibitor zVAD-fmk, prevented segmentation of the nucleus, indicating that these cells undergo autophagy during maturation. Therefore, human neutrophils may undergo spontaneous autophagic cell death rather than apoptosis, during which autophagy may be essential for both maturation and death.
Mechanical loading of desmosomes depends on the magnitude and orientation of external stress
Authors: Price Andrew J. , Cost Anna-Lena , Ungewiß Hanna , Waschke Jens , Dunn Alexander R. , Grashoff Carsten 
Published: December 2018

AbstractDesmosomes are intercellular adhesion complexes that connect the intermediate filament cytoskeletons of neighboring cells, and are essential for the mechanical integrity of mammalian tissues. Mutations in desmosomal proteins cause severe human pathologies including epithelial blistering and heart muscle dysfunction. However, direct evidence for their load-bearing nature is lacking. Here we develop Förster resonance energy transfer (FRET)-based tension sensors to measure the forces experienced by desmoplakin, an obligate desmosomal protein that links the desmosomal plaque to intermediate filaments. Our experiments reveal that desmoplakin does not experience significant tension under most conditions, but instead becomes mechanically loaded when cells are exposed to external mechanical stresses. Stress-induced loading of desmoplakin is transient and sensitive to the magnitude and orientation of the applied tissue deformation, consistent with a stress absorbing function for desmosomes that is distinct from previously analyzed cell adhesion complexes.
Deoxyribose and deoxysugar derivatives from photoprocessed astrophysical ice analogues and comparison to meteorites
Authors: Nuevo Michel , Cooper George , Sandford Scott A. 
Published: December 2018

AbstractSugars and their derivatives are essential to all terrestrial life. Their presence in meteorites, together with amino acids, nucleobases, amphiphiles, and other compounds of biological importance, may have contributed to the inventory of organics that played a role in the emergence of life on Earth. Sugars, including ribose (the sugar of RNA), and other sugar derivatives have been identified in laboratory experiments simulating photoprocessing of ices under astrophysical conditions. In this work, we report the detection of 2-deoxyribose (the sugar of DNA) and several deoxysugar derivatives in residues produced from the ultraviolet irradiation of ice mixtures consisting of H2O and CH3OH. The detection of deoxysugar derivatives adds to the inventory of compounds of biological interest that can form under astrophysical conditions and puts constraints on their abiotic formation pathway. Finally, we report that some of the deoxysugar derivatives found in our residues are also newly identified in carbonaceous meteorites.
Bioconjugation strategy for cell surface labelling with gold nanostructures designed for highly localized pH measurement
Authors: Puppulin Leonardo , Hosogi Shigekuni , Sun Hongxin , Matsuo Kazuhiko , Inui Toshio , Kumamoto Yasuaki , Suzaki Toshinobu , Tanaka Hideo , Marunaka Yoshinori 
Published: December 2018

AbstractRegulation of intracellular pH is critically important for many cellular functions. The quantification of proton extrusion in different types of cells and physiological conditions is pivotal to fully elucidate the mechanisms of pH homeostasis. Here we show the use of gold nanoparticles (AuNP) to create a high spatial resolution sensor for measuring extracellular pH in proximity of the cell membrane. We test the sensor on HepG2 liver cancer cells and MKN28 gastric cancer cells before and after inhibition of Na+/H+ exchanger. The gold surface conjugation strategy is conceived with a twofold purpose: i) to anchor the AuNP to the membrane proteins and ii) to quantify the local pH from AuNP using surface enhanced Raman spectroscopy (SERS). The nanometer size of the cell membrane anchored sensor and the use of SERS enable us to visualize highly localized variation of pH induced by H+ extrusion, which is particularly upregulated in cancer cells.
Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis
Authors: Rudkin Fiona M. , Raziunaite Ingrida , Workman Hillary , Essono Sosthene , Belmonte Rodrigo , MacCallum Donna M. , Johnson Elizabeth M. , Silva Lisete M. , Palma Angelina S. , Feizi Ten , Jensen Allan , Erwig Lars P. , Gow Neil A. R. 
Published: December 2018

AbstractThe high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.
Asphalt granulate coating for roadsides
Authors: Sakhapov Rustem , Makhmutov Marat , Nikolaeva Regina , Gatiatullin Muhammat 
Published: December 2018

The safety of road trains and other vehicles, the cost of maintenance and repair of roads largely depend on how well designed and calculated the design of the pavement. The research of many scientists and engineers is devoted to the design of pavement.
Quantitative and qualitative changes in traffic flows cannot but affect the actual condition of road pavement and coatings, as well as the requirements for their operational condition. Road clothing is a structure that includes several layers of different materials, the base of which is the ground of the roadbed.
The idea of deformability of the soil mass as a continuous homogeneous half-space has been developed for a long time and now continues to improve. Different technologies for the restoration of structural layers of the road surface were considered. On the basis of this work, it is possible to analyze the study of the state of roadsides and can be given suggestions for improving the calculation of the structures of their strengthening. As a result of the study, the reduction coefficients for the calculated vehicle were calculated with a different combination of longitudinal and transverse slopes of the roadway, a proportional increase in which will allow obtaining the reduction coefficients for all vehicles available in the flow, taking into account the slopes of the roadway.
Influence of extraction conditions on the recovery lipids extracted from the dry biomass of duckweed Lemna minor
Authors: Smyatskaya Yulia , Politaeva Natalia , Toumi Amira , Olshanskaya Lubov 
Published: December 2018

Previous studies on the composition of lipid content of higher aquatic plants can be found in the literature. The present work aims to study the effect of various solvent extraction systems on the recovery of lipids extracted from the dry biomass of Lemna minor, using the same polar solvent (ethanol) and variating the non-polar solvent as follow: methanol-ethanol, chloroform-ethanol, hexane-ethanol, diethyl ether-ethanol, petroleum ether-ethanol at different volume ratio. The goal is to select a Sohxlet extraction method that shortens the extraction duration and increases the lipid recovery using various solvents. To intensify the extraction process, homogenization was used as a cell disruption method.
It is shown that the yield of total lipids is increased by using homogenization from 4.6% to 6.0%. When studying the influence of the solvent system, the highest yield of total lipids was obtained by using hexane-ethanol with a volume ration of 1:1 (8.0% total lipids by dry mass). The yield of lipids recovered from dry biomass of Lemna minor increases by increasing the extraction time. The optimum extraction time was found to be no more than 300 minutes. The composition of the lipid fraction is mainly represented by sterols, fatty acids and triglycerides.
An Overview on Genistein and its Various Formulations
Authors: Jaiswal Neha , Akhtar Juber , Singh Satya Prakash , Ahsan Farogh ,   Badruddeen
Published: December 2018

AbstractGenistein is the natural isoflavone and a phytoestrogen with a broad range of pharmacological properties, such as tyrosine and topoisomerase inhibition. It also induces apoptosis and cell proliferation inhibition, differentiates cancer cells. Added health benefits include the reduction of osteoporosis by suppressing osteoclasts and lymphocyte functions, decreased the risk of cardiovascular attacks and relieved postmenopausal problems. Genistein traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast, prostate and lung cancer. Numerous factors comprising genetic, epigenetic and transcriptomic alterations are evidenced to be responsible for breast, prostate and lung cancer. In present review, an overview on genistein, the various analytical methods and drug delivery approaches to determine genistein in the formulations are discussed. It may help to develop novel formulations with better solubility and bioavailability of genistein. The tumor cell scan may be targeted to form a stable genistein formulation.
Der Mini-Audio-Test (MAT) – eine Screeningmethode auf
Schwerhörigkeit für Haus- und Fachärzte
Authors: Löhler Jan , Lehmann Martin , Segler Veronika , Volkenstein Stefan , Battmer Rolf-Dieter , Ernst Arneborg , Gräbner Frederike , Schlattmann Peter , Schönweiler Rainer , Wollenberg Barbara , Dazert Stefan 
Published: December 2018

Zusammenfassung
Hintergrund In Deutschland leiden etwa 15 Millionen Menschen an einer
Schwerhörigkeit (SH), doch nur 16 % tragen Hörgeräte. Diese Unterversorgung kann
für die Betroffenen zu schwerwiegenden Folgen (soziale Isolation, Depression,
Förderung einer Demenz etc.) führen. Ein frühzeitiges und flächendeckendes
Hörscreening ab dem 50. Lebensjahr kann dies verbessern. In dieser Studie wurde
der Mini-Audio-Test (MAT), ein sechs Fragen zum subjektiven Hörverlust (HV)
umfassender Test mit dreistufiger Antwortskala, an einem Normalkollektiv
überprüft (Sensitivität (Se), Spezifität (Sp), positiver prädiktiver Wert
(PPW)).
Methode Es wurden 943 Patienten (älter als 50 Jahre) ohne bekannte
Ohrenerkrankungen mittels MAT befragt, zum Vergleich die Hörschwellen
tonaudiometrisch ermittelt und die Se, Sp und der PPW zur Detektion eines
relevanten HV durch den MAT für die Altersklassen < 60 Jahre (AG1) und ≥ 60
Jahre (AG2) mittels binomialer Proportionen ermittelt.
Ergebnisse Die Se lag für AG1 bei 0,66, die Sp bei 0,61, der PW bei 0,60,
für die AG2 lag die Se bei 0,47, die Sp bei 0,80, der PPW bei 0,89.
Schlussfolgerung Entsprechend der vorliegenden Ergebnisse wird der Einsatz
des MAT als Screeningmethode für Nicht-HNO-Ärzte zur Detektion von
schwerhörenden Patienten ab dem 50. Lebensjahr vorgeschlagen. Hierdurch ließen
sich auch schwerwiegende Begleiterkrankungen wie Minderung der kognitiven
Leistungsfähigkeit, Sturzrisiko, Depression und Demenz positiv beeinflussen.
Uniform bounds for solutions to elliptic problems on simply connected planar domains
Authors: Battaglia Luca 
Published: December 2018

We consider the following elliptic problems on simply connected planar domains:

{

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\begin{equation*} \left \{\begin {array}{ll}-\Delta u=\lambda |x|^{2\alpha }K(x)e^u&\text {in }\Omega \\u=0&\text {on }\partial \Omega \end{array}\right . ;\quad \quad \left \{\begin {array}{ll}-\Delta u=|x|^{2\alpha }K(x)u^p&\text {in }\Omega \\u>0&\text {in }\Omega \\u=0&\text {on }\partial \Omega \end{array}\right . \end{equation*}

with

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\alpha >-1,\lambda >0,p>1,0>K(x)\in C^1\left (\overline \Omega \right )

.

We show that any solution to each problem must satisfy a uniform bound on the mass, which is given, respectively, by

λ

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|

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\lambda \int _\Omega |x|^{2\alpha }K(x)e^u\mathrm dx

and

p

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u

p
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p\int _\Omega |x|^{2\alpha }K(x)u^{p+1}\mathrm dx

. The same results apply to some systems and more general nonlinearities.

The proofs are based on the Riemann mapping theorem and a Pohožaev-type identity.
In silico error correction improves cfDNA mutation calling
Authors: Kim Chang Sik , Mohan Sumitra , Ayub Mahmood , Rothwell Dominic G , Dive Caroline , Brady Ged , Miller Crispin 
Published: December 2018

Abstract

Motivation
Circulating-free DNA (cfDNA) profiling by sequencing is an important minimally invasive protocol for monitoring the mutation profile of solid tumours in cancer patients. Since the concentration of available cfDNA is limited, sample library generation relies on multiple rounds of PCR amplification, during which the accumulation of errors results in reduced sensitivity and lower accuracy.

Results
We present PCR Error Correction (PEC), an algorithm to identify and correct errors in short read sequencing data. It exploits the redundancy that arises from multiple rounds of PCR amplification. PEC is particularly well suited to applications such as single-cell sequencing and circulating tumour DNA (ctDNA) analysis, in which many cycles of PCR are used to generate sufficient DNA for sequencing from small amounts of starting material. When applied to ctDNA analysis, PEC significantly improves mutation calling accuracy, achieving similar levels of performance to more complex strategies that require additional protocol steps and access to calibration DNA datasets.

Availability and implementation
PEC is available under the GPL-v3 Open Source licence, and is freely available from: https://github.com/CRUKMI-ComputationalBiology/PCR_Error_Correction.git.

Supplementary information
Supplementary data are available at Bioinformatics online.
Accurate and efficient estimation of smallP-values with the cross-entropy method: applications in genomic data analysis
Authors: Shi Yang , Wang Mengqiao , Shi Weiping , Lee Ji-Hyun , Kang Huining , Jiang Hui 
Published: December 2018

AbstractMotivationSmall P-values are often required to be accurately estimated in large-scale genomic studies for the adjustment of multiple hypothesis tests and the ranking of genomic features based on their statistical significance. For those complicated test statistics whose cumulative distribution functions are analytically intractable, existing methods usually do not work well with small P-values due to lack of accuracy or computational restrictions. We propose a general approach for accurately and efficiently estimating small P-values for a broad range of complicated test statistics based on the principle of the cross-entropy method and Markov chain Monte Carlo sampling techniques.ResultsWe evaluate the performance of the proposed algorithm through simulations and demonstrate its application to three real-world examples in genomic studies. The results show that our approach can accurately evaluate small to extremely small P-values (e.g. 10-6 to 10-100). The proposed algorithm is helpful for the improvement of some existing test procedures and the development of new test procedures in genomic studies.Availability and implementationR programs for implementing the algorithm and reproducing the results are available at: https://github.com/shilab2017/MCMC-CE-codes.Supplementary informationSupplementary data are available at Bioinformatics online.
Capsule network for protein post-translational modification site prediction
Authors: Wang Duolin , Liang Yanchun , Xu Dong 
Published: December 2018

Abstract

Motivation
Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions. The prediction accuracy of the existing methods has significant room for improvement. A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.

Results
We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites. The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data. The capsule length also gives an accurate estimate for the confidence of the PTM prediction. We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided. In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families. Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.

Availability and implementation
The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.

Supplementary information
Supplementary data are available at Bioinformatics online.