bluuebunny/crossref_metadata_2025_split huggingface dataset:
α7 nicotinic acetylcholine receptor upregulation by anti-apoptotic Bcl-2 proteins
Authors: Dawe G. Brent , Yu Hong , Gu Shenyan , Blackler Alissa N. , Matta Jose A. , Siuda Edward R. , Rex Elizabeth B. , Bredt David S. 
Published: June 2019

AbstractNicotinic acetylcholine receptors (nAChRs) mediate and modulate synaptic transmission throughout the brain, and contribute to learning, memory, and behavior. Dysregulation of α7-type nAChRs in neuropsychiatric as well as immunological and oncological diseases makes them attractive targets for pharmaceutical development. Recently, we identified NACHO as an essential chaperone for α7 nAChRs. Leveraging the robust recombinant expression of α7 nAChRs with NACHO, we utilized genome-wide cDNA library screening and discovered that several anti-apoptotic Bcl-2 family proteins further upregulate receptor assembly and cell surface expression. These effects are mediated by an intracellular motif on α7 that resembles the BH3 binding domain of pro-apoptotic Bcl-2 proteins, and can be blocked by BH3 mimetic Bcl-2 inhibitors. Overexpression of Bcl-2 member Mcl-1 in neurons enhanced surface expression of endogenous α7 nAChRs, while a combination of chemotherapeutic Bcl2-inhibitors suppressed neuronal α7 receptor assembly. These results demonstrate that Bcl-2 proteins link α7 nAChR assembly to cell survival pathways.
Integrative inference of subclonal tumour evolution from single-cell and bulk sequencing data
Authors: Malikic Salem , Jahn Katharina , Kuipers Jack , Sahinalp S. Cenk , Beerenwinkel Niko 
Published: June 2019

AbstractUnderstanding the clonal architecture and evolutionary history of a tumour poses one of the key challenges to overcome treatment failure due to resistant cell populations. Previously, studies on subclonal tumour evolution have been primarily based on bulk sequencing and in some recent cases on single-cell sequencing data. Either data type alone has shortcomings with regard to this task, but methods integrating both data types have been lacking. Here, we present B-SCITE, the first computational approach that infers tumour phylogenies from combined single-cell and bulk sequencing data. Using a comprehensive set of simulated data, we show that B-SCITE systematically outperforms existing methods with respect to tree reconstruction accuracy and subclone identification. B-SCITE provides high-fidelity reconstructions even with a modest number of single cells and in cases where bulk allele frequencies are affected by copy number changes. On real tumour data, B-SCITE generated mutation histories show high concordance with expert generated trees.
A fast and specific fluorescent probe for thioredoxin reductase that works via disulphide bond cleavage
Authors: Li Xinming , Zhang Baoxin , Yan Chaoxian , Li Jin , Wang Song , Wei Xiangxu , Jiang Xiaoyan , Zhou Panpan , Fang Jianguo 
Published: June 2019

AbstractSmall molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.
Machine-learning-assisted discovery of polymers with high thermal conductivity using a molecular design algorithm
Authors: Wu Stephen , Kondo Yukiko , Kakimoto Masa-aki , Yang Bin , Yamada Hironao , Kuwajima Isao , Lambard Guillaume , Hongo Kenta , Xu Yibin , Shiomi Junichiro , Schick Christoph , Morikawa Junko , Yoshida Ryo 
Published: June 2019

AbstractThe use of machine learning in computational molecular design has great potential to accelerate the discovery of innovative materials. However, its practical benefits still remain unproven in real-world applications, particularly in polymer science. We demonstrate the successful discovery of new polymers with high thermal conductivity, inspired by machine-learning-assisted polymer chemistry. This discovery was made by the interplay between machine intelligence trained on a substantially limited amount of polymeric properties data, expertise from laboratory synthesis and advanced technologies for thermophysical property measurements. Using a molecular design algorithm trained to recognize quantitative structure—property relationships with respect to thermal conductivity and other targeted polymeric properties, we identified thousands of promising hypothetical polymers. From these candidates, three were selected for monomer synthesis and polymerization because of their synthetic accessibility and their potential for ease of processing in further applications. The synthesized polymers reached thermal conductivities of 0.18–0.41 W/mK, which are comparable to those of state-of-the-art polymers in non-composite thermo-plastics.
High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer
Authors: Bertelsen Birgitte , Tuxen Ida Viller , Yde Christina Westmose , Gabrielaite Migle , Torp Mathias Husted , Kinalis Savvas , Oestrup Olga , Rohrberg Kristoffer , Spangaard Iben , Santoni-Rugiu Eric , Wadt Karin , Mau-Sorensen Morten , Lassen Ulrik , Nielsen Finn Cilius 
Published: June 2019

AbstractGenomic screening of cancer patients for predisposing variants is traditionally based on age at onset, family history and type of cancer. Whereas the clinical guidelines have proven efficient in identifying families exhibiting classical attributes of hereditary cancer, the frequency of patients with alternative presentations is unclear. We identified and characterized germline variants in 636 patients with advanced solid cancer using whole exome sequencing. Pathogenic and likely pathogenic germline variants among 168 genes associated with hereditary cancer were considered. These variants were identified in 17.8% of the patients and within a wide range of cancer types. In particular, patients with mesothelioma, ovarian cancer, cervical cancer, urothelial cancer, and cancer of unknown primary origin displayed high frequencies of pathogenic variants. Variants were predominantly found in DNA-repair pathways and about half were within genes involved in homologous recombination repair. Twenty-two BRCA1 and BRCA2 germline variants were identified in 12 different cancer types, of which 10 (45%) were not previously identified in these patients based on the current clinical guidelines. Loss of heterozygosity and somatic second hits were identified in several of the affected genes, supporting possible causality for cancer development. A potential treatment target based on the pathogenic germline variant could be suggested in 25 patients (4%). The study demonstrates a high frequency of pathogenic germline variants in the homologous recombination pathway in patients with advanced solid cancers. We infer that genetic screening in this group of patients may reveal high-risk families and identify patients with potential PARP inhibitor sensitive tumors.
Prediction of Sub-Monomer A2 Domain Dynamics of the von Willebrand Factor by Machine Learning Algorithm and Coarse-Grained Molecular Dynamics Simulation
Authors: Morabito Michael J. , Usta Mustafa , Cheng Xuanhong , Zhang Xiaohui F. , Oztekin Alparslan , Webb Edmund B. 
Published: June 2019

AbstractWe develop a machine learning tool useful for predicting the instantaneous dynamical state of sub-monomer features within long linear polymer chains, as well as extracting the dominant macromolecular motions associated with sub-monomer behaviors of interest. We employ the tool to better understand and predict sub-monomer A2 domain unfolding dynamics occurring amidst the dominant large-scale macromolecular motions of the biopolymer von Willebrand Factor (vWF) immersed in flow. Results of coarse-grained Molecular Dynamics (MD) simulations of non-grafted vWF multimers subject to a shearing flow were used as input variables to a Random Forest Algorithm (RFA). Twenty unique features characterizing macromolecular conformation information of vWF multimers were used for training the RFA. The corresponding responses classify instantaneous A2 domain state as either folded or unfolded, and were directly taken from coarse-grained MD simulations. Three separate RFAs were trained using feature/response data of varying resolution, which provided deep insights into the highly correlated macromolecular dynamics occurring in concert with A2 domain unfolding events. The algorithm is used to analyze results of simulation, but has been developed for use with experimental data as well.
Automated detection of third molars and mandibular nerve by deep learning
Authors: Vinayahalingam Shankeeth , Xi Tong , Bergé Stefaan , Maal Thomas , de Jong Guido 
Published: June 2019

AbstractThe approximity of the inferior alveolar nerve (IAN) to the roots of lower third molars (M3) is a risk factor for the occurrence of nerve damage and subsequent sensory disturbances of the lower lip and chin following the removal of third molars. To assess this risk, the identification of M3 and IAN on dental panoramic radiographs (OPG) is mandatory. In this study, we developed and validated an automated approach, based on deep-learning, to detect and segment the M3 and IAN on OPGs. As a reference, M3s and IAN were segmented manually on 81 OPGs. A deep-learning approach based on U-net was applied on the reference data to train the convolutional neural network (CNN) in the detection and segmentation of the M3 and IAN. Subsequently, the trained U-net was applied onto the original OPGs to detect and segment both structures. Dice-coefficients were calculated to quantify the degree of similarity between the manually and automatically segmented M3s and IAN. The mean dice-coefficients for M3s and IAN were 0.947 ± 0.033 and 0.847 ± 0.099, respectively. Deep-learning is an encouraging approach to segment anatomical structures and later on in clinical decision making, though further enhancement of the algorithm is advised to improve the accuracy.
Open chromatin dynamics in prosensory cells of the embryonic mouse cochlea
Authors: Wilkerson Brent A. , Chitsazan Alex D. , VandenBosch Leah S. , Wilken Matthew S. , Reh Thomas A. , Bermingham-McDonogh Olivia 
Published: June 2019

AbstractHearing loss is often due to the absence or the degeneration of hair cells in the cochlea. Understanding the mechanisms regulating the generation of hair cells may therefore lead to better treatments for hearing disorders. To elucidate the transcriptional control mechanisms specifying the progenitor cells (i.e. prosensory cells) that generate the hair cells and support cells critical for hearing function, we compared chromatin accessibility using ATAC-seq in sorted prosensory cells (Sox2-EGFP+) and surrounding cells (Sox2-EGFP−) from E12, E14.5 and E16 cochlear ducts. In Sox2-EGFP+, we find greater accessibility in and near genes restricted in expression to the prosensory region of the cochlear duct includingSox2,Isl1,Eya1andPou4f3. Furthermore, we find significant enrichment for the consensus binding sites of Sox2, Six1 and Gata3—transcription factors required for prosensory development—in the open chromatin regions. Over 2,200 regions displayed differential accessibility with developmental time in Sox2-EGFP+cells, with most changes in the E12-14.5 window. Open chromatin regions detected in Sox2-EGFP+cells map to over 48,000 orthologous regions in the human genome that include regions in genes linked to deafness. Our results reveal a dynamic landscape of open chromatin in prosensory cells with potential implications for cochlear development and disease.
Hearing loss in humans drinking tube well water with high levels of iron in arsenic–polluted area
Authors: He Tingchao , Ohgami Nobutaka , Li Xiang , Yajima Ichiro , Negishi-Oshino Reina , Kato Yoko , Ohgami Kyoko , Xu Huadong , Ahsan Nazmul , Akhand Anwarul Azim , Kato Masashi 
Published: June 2019

AbstractWell water for drinking with increased levels of iron in arsenic-polluted areas has been reported worldwide. Oral exposure to arsenic has been shown to be associated with hearing loss, while there is no evidence for an association between excessive exposure to iron and hearing loss in humans. In this study, we determined iron and arsenic levels in biological samples and hearing levels by pure tone audiometry (PTA) in subjects in a control area and an arsenic-polluted area in Bangladesh. The iron level in well water in the arsenic-polluted area was significantly higher than that in piped supply water in the control area. Subjects in the polluted area (n = 109), who had higher iron and arsenic levels in hair and toenails than those in subjects in the control area (n = 36), had an increased risk of hearing loss at 8 kHz and 12 kHz after adjustments for age, gender, smoking and BMI. Significant associations of the exposure group with hearing loss at 8 kHz and 12 kHz remained after further adjustment for arsenic levels in toenails and hair. Thus, this pilot study showed that excessive exposure to iron via drinking water is a potential risk for hearing loss in humans.
Dynamically encircling exceptional points in a three-mode waveguide system
Authors: Zhang Xu-Lin , Chan C. T. 
Published: June 2019

AbstractDynamically encircling exceptional points (EPs) in non-Hermitian systems has attracted considerable attention recently, but all previous studies focused on two-state systems, and the dynamics in more complex multi-state systems is yet to be investigated. Here we consider a three-mode non-Hermitian waveguide system possessing two EPs, and study the dynamical encircling of each single EP and both EPs, the latter of which is equivalent to the dynamical encircling of a third-order EP that has a cube-root behavior of eigenvalue perturbations. We find that the dynamics depends on the location of the starting point of the loop, instead of the order of the EP encircled. Compared with two-state systems, the dynamical processes in multi-state systems exhibit more non-adiabatic transitions owing to the more complex topological structures of energy surfaces. Our findings enrich the understanding of the physics of multi-state non-Hermitian systems and may lead to the design of new wave manipulation schemes.
Novel Word Learning in Children Who Are Bilingual: Comparison to Monolingual Peers
Authors: Alt Mary , Arizmendi Genesis Dominique , Gray Shelley , Hogan Tiffany Patrice , Green Samuel , Cowan Nelson 
Published: June 2019

Purpose
We compared novel word learning in 2nd-grade children with typical development who were Spanish–English bilinguals to English monolinguals to understand word learning in bilingual children.

Method

Children (monolinguals
n
= 167, bilinguals
n
= 76) engaged in 5 computer-based tasks that assessed word learning in 6 different contexts. The tasks measured children's ability to link novel names with novel objects/actions, make decisions about the accuracy of those names and objects/actions, recognize the semantic features of the objects/actions, and produce the novel names. For analysis, we used Bayesian repeated-measures analyses of covariance with Bayesian independent-samples
t
tests to clarify interactions.

Results
Monolingual and bilingual children differed in some, but not most, word learning situations. There was at least moderate evidence that bilingual children were less accurate at naming in 1 condition and at detecting mispronunciations in 3 of 6 contexts and were less accurate at judging semantic features of a referent when that referent was paired with orthographic information.

Discussion
Among children with typical development, there were few differences in novel word learning between monolingual and bilingual participants. When differences did occur, they suggested that bilinguals were more accepting of phonological variations of word productions than their monolingual peers.
Contributions of Fibroblasts, Extracellular Matrix, Stiffness, and Mechanosensing to Hepatocarcinogenesis
Authors: Filliol Aveline , Schwabe Robert F. 
Published: June 2019

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. A unique feature of liver cancer is its close association with liver fibrosis. About 90% of HCCs develop in advanced liver fibrosis or cirrhosis, suggesting an important role for the fibrotic microenvironment in driving HCC development. Here, the authors will discuss functional contributions of liver fibrosis to the development of HCC, focusing on mechanisms through which fibrosis may promote HCC development such as hepatic stellate cell-derived extracellular matrix, growth factors, and cytokines, stiffness-induced signaling pathways, and immunosuppression. Better understanding of these factors in HCC development and progression may provide the basis for novel stromal-based therapies for tumor prevention or therapy.
Conquering the Rock—A Retrospective Single-Center Experience of the Transapical Petrosal Transtentorial (Kawase) Approach: Operative Technique and Impact on Cranial Nerve Function
Authors: Volovici V. , Dammers R. , Dirven C. M. F. , Delwel E. J. 
Published: June 2019

AbstractSince its description in 1985, the transapical petrosal transtentorial or Kawase approach has become a viable option of approaching lesions located in and around the apex of the petrous bone, Meckel's cave, and the anterolateral surface of the brain stem while preserving cranial nerve function. At the Brain Tumor Center, Erasmus MC, 25 patients were treated using the Kawase approach between 2004 and 2018 for various indications, including petroclival meningiomas, chondrosarcomas, pontine cavernomas, trigeminal schwannomas, and posterior circulation aneurysms. Hearing preservation was achieved in all patients; new abducens nerve and trochlear nerve palsies were present in three and six patients, respectively, of which a total of eight required ophthalmological correction. Seven patients experienced a cerebrospinal fluid fistula postoperatively, but this complication appeared self-limiting in all cases, with one patient experiencing secondary meningitis. After modifying our closure technique, the rate of fistulas dropped to zero. The observed direct postoperative mortality was 4% (one patient), although not related to the approach itself. In conclusion, the Kawase approach is a highly complex, but essential middle fossa approach, extremely robust, and able to serve a wide array of pathologies together with its extensions. It is very accurate for performing hearing preservation surgery, but not without caveats and inherent risk of complications.
Endoscopic Endonasal Transpterygoid Approach to Sphenoid Sinus Lateral Recess Defects
Authors: Bozkurt Gülpembe , Turri-Zanoni Mario , Coden Elisa , Russo Federico , Elhassan Hassan Ahmed , Gallo Stefania , Zocchi Jacopo , Bignami Maurizio , Locatelli Davide , Castelnuovo Paolo 
Published: June 2019

Background Lesions affecting sphenoid sinus lateral recess (SSLR) are difficult to visualize and manipulate through the transnasal routes, especially when the sinus is highly pneumatized. External approaches to this area involve extensive surgery and are associated with significant morbidity. The aims of this study are to present our experience with the endoscopic transpterygoid approach as a method for approaching lesions of the SSLR and to evaluate the outcomes of this procedure.Methods Clinical charts of patients who had lesions in the SSLR and who were treated at our institution from September 1998 to June 2018 were retrospectively reviewed. All these patients were managed by the endoscopic endonasal transpterygoid approach.Results Thirty-nine patients were identified. No cerebrospinal fluid leak recurrences were observed during follow-up (range: 1–19.7 years; median: 2.3 years). Hypoesthesia (temporary, 1; persistent, 4) in the region innervated by the maxillary branch of the trigeminal nerve was detected in five (12.8%) patients, while symptoms due to the Vidian nerve damage (dry eye, 3; dry nasal mucosa, 1) were present in four (10%) patients.Conclusions Although the endoscopic endonasal transpterygoid approach is an excellent corridor for dealing with lesions of the SSLR, limited rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention should be discussed during preoperative counselling.
An effector from cotton bollworm oral secretion impairs host plant defense signaling
Authors: Chen Chun-Yu , Liu Yao-Qian , Song Wei-Meng , Chen Dian-Yang , Chen Fang-Yan , Chen Xue-Ying , Chen Zhi-Wen , Ge Sheng-Xiang , Wang Chen-Zhu , Zhan Shuai , Chen Xiao-Ya , Mao Ying-Bo 
Published: June 2019

Significance
Plants recognize insect-derived molecules and make the accurate defense response during herbivory. However, insects release effectors that disturb host plant defense responses for fitness. Effectors are crucial components in biotic interactions. We identified a caterpillar-derived effector (HARP1) from oral secretion of cotton bollworm, a devastating agricultural pest. HARP1 is released from larvae to plant leaves during feeding and is able to migrate from wounding site into plant cells automatically. HARP1 interacts with JASMONATE-ZIM-domain (JAZ) proteins, the suppressor of Jasmonate (JA) pathway, and blocks signaling transduction by preventing JAZ degradation. HARP1-like proteins are widely distributed and have conserved function in noctuids, and they may contribute to insect adaptation to host plants during coevolution.
Translation, a Tudor political instrument
Authors: Valdeón Roberto A. 
Published: June 2019

AbstractStarting with an overview of F. O. Matthiessen’s work on the role of translation during the Elizabethan period, this article delves into the paratexts of the translations of Spanish colonial texts by Richard Hakluyt, Edward Grimeston, Michael Lok and John Frampton to discuss the underlying reasons why Spanish accounts of the conquest were rendered into English. The analysis of the dedications and addresses shows that, although these translations may have served to express admiration for the Spanish conquerors or to criticize their actions, the ultimate goals of these texts were to encourage England to replicate the Spanish empire in the Americas, on the one hand, and to obtain social, political and economic benefits for the translators, on the other.