bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kojiglycosylceramide commonly contained in Japanese traditional fermented foods alters cholesterol metabolism in obese mice
Authors: Hamajima Hiroshi , Tanaka Masaru , Miyagawa Miyuki , Sakamoto Mayuko , Nakamura Tsuyoshi , Yanagita Teruyoshi , Nishimukai Megumi , Mitsutake Susumu , Nakayama Jiro , Nagao Koji , Kitagaki Hiroshi 
Published: December 2018

ABSTRACTKoji, which is manufactured by proliferating non-pathogenic fungus Aspergillus oryzae on steamed rice, is the base for Japanese traditional fermented foods. We have revealed that koji and related Japanese fermented foods and drinks such as amazake, shio-koji, unfiltered sake and miso contain abundant glycosylceramide. Here, we report that feeding of koji glycosylceramide to obese mice alters the cholesterol metabolism . Liver cholesterol was significantly decreased in obese mice fed with koji glycosylceramide. We hypothesized that their liver cholesterol was decreased because it was converted to bile acids. Consistent with the hypothesis, many bile acids were increased in the cecum and feces of obese mice fed with koji glycosylceramide. Expressions of CYP7A1 and ABCG8 involved in the metabolism of cholesterol were significantly increased in the liver of mice fed with koji glycosylceramide. Therefore, it was considered that koji glycosylceramide affects the cholesterol metabolism in obese mice.
Optimal proximal augmented Lagrangian method and its application to full Jacobian splitting for multi-block separable convex minimization problems
Authors: He Bingsheng , Ma Feng , Yuan Xiaoming 
Published: December 2018

Abstract
The augmented Lagrangian method (ALM) is fundamental in solving convex programming problems with linear constraints. The proximal version of ALM, which regularizes ALM’s subproblem over the primal variable at each iteration by an additional positive-definite quadratic proximal term, has been well studied in the literature. In this paper we show that it is not necessary to employ a positive-definite quadratic proximal term for the proximal ALM and the convergence can be still ensured if the positive definiteness is relaxed to indefiniteness by reducing the proximal parameter. An indefinite proximal version of the ALM is thus proposed for the generic setting of convex programming problems with linear constraints. We show that our relaxation is optimal in the sense that the proximal parameter cannot be further reduced. The consideration of indefinite proximal regularization is particularly meaningful for generating larger step sizes in solving ALM’s primal subproblems. When the model under discussion is separable in the sense that its objective function consists of finitely many additive function components without coupled variables, it is desired to decompose each ALM’s subproblem over the primal variable in Jacobian manner, replacing the original one by a sequence of easier and smaller decomposed subproblems, so that parallel computation can be applied. This full Jacobian splitting version of the ALM is known to be not necessarily convergent, and it has been studied in the literature that its convergence can be ensured if all the decomposed subproblems are further regularized by sufficiently large proximal terms. But how small the proximal parameter could be is still open. The other purpose of this paper is to show the smallest proximal parameter for the full Jacobian splitting version of ALM for solving multi-block separable convex minimization models.
Firms’ method of pay and the retention of apprentices
Authors: Rinawi Miriam , Backes-Gellner Uschi 
Published: December 2018

AbstractThe new training literature views regulated labour markets as critical for firms’ willingness to participate in apprenticeship training. These regulations allow training firms to retain their apprenticeship graduates at the end of the training period and recoup training costs. Yet, in spite of an only loosely regulated labour market, many Swiss firms offer and pay for training. Using representative data from a large employer–employee survey, we investigate whether these firms use performance pay to retain their graduates. We find that both the magnitude and the likelihood of performance pay are significantly related to a firm’s retention success.
Partial Scleral Rupture Presenting 4 Years After Laser in Situ Keratomileusis
Authors: LaMattina Kara C. , Feder Robert S. , Koreishi Anjum F. , Goldstein Debra A. 
Published: December 2018

Purpose:
To report a case of partial scleral rupture after laser in situ keratomileusis (LASIK) surgery.

Methods:
This is a retrospective case report describing a late complication of LASIK surgery.

Results:
A 32-year-old white woman with a history of LASIK surgery performed with a mechanical microkeratome 4 years previously presented for evaluation of partial bilateral scleral ruptures. An arcuate filtering bleb along the contour of the cornea was found on the right eye with associated hypotony and corneal astigmatism. There were no signs or symptoms of prior inflammation, and rheumatologic workup was negative. Imaging revealed scleral microbreaks in the absence of adjacent thinning.

Conclusions:
The pattern and location of thinning without findings consistent with inflammatory disease suggest that the partial bilateral scleral rupture was because of mechanical damage at the time of LASIK, possibly compounded by the hormonal changes of pregnancy.
Congenital Dacryocystocele: A Major Review
Authors: Singh Swati , Ali Mohammad Javed 
Published: December 2018

Purpose:
To provide a systematic review of the literature on congenital dacryocystoceles (CDCs) and summarize their presentations, investigations, management, and outcomes.

Methods:
The authors performed a PubMed search of all articles published in English on CDCs. Data captured include demographics, clinical presentations, investigations, management modalities, complications, and outcomes. Fourteen major series (10 or more than 10 cases) and 89 isolated case reports/series on CDCs with a collective patient pool of 1,063 were studied in detail. Specific emphasis was laid on addressing the controversial issues including initial conservative versus surgical management and the role of endoscopic evaluation.

Results:
Numerous terminologies have been used to describe CDC. Congenital dacryocystoceles are rare variants of congenital nasolacrimal duct obstructions and comprise of 0.1% to 0.3% of all such cases. There is a female predilection (64.2%, 683/1,063) and the mean age at presentation is at 7 days of birth. Initial conservative treatment can be a viable option in the absence of an acute dacryocystitis or a respiratory distress. Endoscopy-assisted probing appears to have better outcomes as compared with the in-office probing. Congenital dacryocystoceles with acute dacryocystitis are preferably managed with intravenous antibiotics and an early probing under endoscopy guidance to avoid missing intranasal cysts. Marsupialization is the preferred technique in the management of intranasal cysts. Silicone intubation was rarely used and has no definitive indications. Dacryocystorhinostomy is very rarely needed in the management of CDC.

Conclusions:
Congenital dacryocystocele is a commonly accepted term and its use should be advocated to enhance uniformity in reporting. Endoscopic evaluation of CDC is useful in the diagnosis and treatment of associated intranasal cysts and enhances the rates of successful outcomes.
More than a flying syringe: Using functional traits in vector-borne disease research
Authors: Cator Lauren J. , Johnson Leah R. , Mordecai Erin A. , Moustaid Fadoua El , Smallwood Thomas R.C. , LaDeau Shannon L. , Johansson Michael A. , Hudson Peter J. , Boots Michael , Thomas Matthew B. , Power Alison G. , Pawar Samraat 
Published: December 2018

AbstractMany important endemic and emerging diseases are vector-borne. The functional traits of vectors affect not just pathogen transmission rates, but also the fitness and population dynamics of these animals themselves. Increasing empirical evidence suggests that vector traits vary significantly at time scales relevant to transmission dynamics. Currently, an understanding of how this variation in key traits impacts transmission is hindered by a lack of both empirical data and theoretical methods for mechanistically incorporating traits into transmission models. Here, we present a framework for incorporating both intrinsic and environment-driven variation in vector traits into empirical and theoretical vector-borne disease research. This framework mechanistically captures the effect of trait variation on vector fitness, the correlation between vector traits, and how these together determine transmission dynamics. We illustrate how trait-based vector-borne disease modelling can make novel predictions, and identify key steps and challenges in the construction, empirical parameterisation and validation of such models, as well as the organization and prioritization of data collection efforts.
Fluorescence Microscopy of Piezo1 in Droplet Hydrogel Bilayers
Authors: Jaggers Oskar B. , Ridone Pietro , Martinac Boris , Baker Matthew A. B. 
Published: December 2018

AbstractMechanosensitive ion channels are membrane gated pores which are activated by mechanical stimuli. The focus of this study is on Piezo1, a newly discovered, large, mammalian, mechanosensitive ion channel, which has been linked to diseases such as dehydrated hereditary stomatocytosis (Xerocytosis) and lymphatic dysplasia. Here we utilize an established in-vitro artificial bilayer system to interrogate single Piezo1 channel activity. The droplet-hydrogel bilayer (DHB) system uniquely allows the simultaneous recording of electrical activity and fluorescence imaging of labelled protein. We successfully reconstituted fluorescently labelled Piezo1 ion channels in DHBs and verified activity using electrophysiology in the same system. We demonstrate successful insertion and activation of hPiezo1-GFP in bilayers of varying composition. Furthermore, we compare the Piezo1 bilayer reconstitution with measurements of insertion and activation of KcsA channels to reproduce the channel conductances reported in the literature. Together, our results showcase the use of DHBs for future experiments allowing simultaneous measurements of ion channel gating while visualising the channel proteins using fluorescence.
Structural basis of sterol recognition by human hedgehog receptor PTCH1
Authors: Qi Chao , Minin Giulio Di , Vercellino Irene , Wutz Anton , Korkhov Volodymyr M. 
Published: December 2018

AbstractHedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4 Å cryo-EM structure of the human PTCH1 bound to ShhNC24II, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by ten sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol sensing domain, SSD, and the SSD-like domain, SSDL, which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters.
Reconstruction of the global neural crest gene regulatory networkin vivo
Authors: Williams Ruth M , Candido-Ferreira Ivan , Repapi Emmanouela , Gavriouchkina Daria , Senanayake Upeka , Telenius Jelena , Taylor Stephen , Hughes Jim , Sauka-Spengler Tatjana 
Published: December 2018

AbstractPrecise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and transient dynamic molecular interactions. Here we present a genome-widein vivoreconstruction of the GRN underlying development of neural crest (NC), an emblematic embryonic multipotent cell population. By coupling NC-specific epigenomic and single-cell transcriptome profiling with genome/epigenome engineeringin vivo, we identify multiple regulatory layers governing NC ontogeny, including NC-specific enhancers and super-enhancers, noveltrans-factors andcis-signatures. Assembling the NC regulome has allowed the comprehensive reverse engineering of the NC-GRN at unprecedented resolution. Furthermore, identification and dissection of divergent upstream combinatorial regulatory codes has afforded new insights into opposing gene circuits that define canonical and neural NC fates. Our integrated approach, allowing dissection of cell-type-specific regulatory circuitsin vivo, has broad implications for GRN discovery and investigation.
Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development
Authors: Hernandez Jose A. , Castro Victoria L. , Reyes-Nava Nayeli , Montes Laura P. , Quintana Anita M. 
Published: December 2018

AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression ofGATA1are not completely characterized. Cholesterol is one potential upstream mediator ofGATA1expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in thehmgcs1gene (Vu57 allele).hmgcs1encodes the first enzyme in the cholesterol synthesis pathway and mutation ofhmgcs1inhibits cholesterol synthesis. We analyzed the number of RBCs inhmgcs1mutants and their wildtype siblings. Mutation ofhmgcs1resulted in a decrease in the number of mature RBCs, which coincides with reducedgata1aexpression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but thatgata1aexpression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.Key PointsThe products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis.Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor.
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma
Authors: Huang Hector H. , Ferguson Ian D. , Thornton Alexis M. , Lam Christine , Lin Yu-Hsiu T. , Bastola Prabhakar , Choudhry Priya , Mariano Margarette C. , Marcoulis Makeba , Malato Julia , Phojanakong Paul , Martin Thomas G. , Wolf Jeffrey L. , Wong Sandy W. , Shah Nina , Hann Byron C. , Brooks Angela N. , Wiita Arun P. 
Published: December 2018

AbstractEnhancing the efficacy of proteasome inhibitors is a central goal in myeloma therapy. We proposed that signaling-level responses after PI would reveal new mechanisms of action that could be therapeutically exploited. Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation was invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrated broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings led us to evaluate direct spliceosome inhibition in myeloma, which synergized with carfilzomib and showed potent anti-tumor activity. Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.SignificanceNew ways to enhance PI efficacy are of major interest. We combine systems-level analyses to discover that PIs specifically interfere with splicing and that myeloma is selectively vulnerable to spliceosome inhibition. We reveal a new approach to advance myeloma therapy and uncover broader roles of splicing modulation in cancer.
Cell Fate Simulation Reveals Cancer Cell Features in the Tumor Microenvironment
Authors: Sato Sachiko , Rancourt Ann , Satoh Masahiko S. 
Published: December 2018

AbstractTo elucidate the dynamic evolution of cancer cell characteristics within the tumor microenvironment (TME), we developed an integrative method combining single-cell tracking, cell fate simulation, and three-dimensional (3D) TME modeling. We began our investigation by analyzing the spatiotemporal behavior of individual cancer cells in cultured pancreatic and cervical cancer cell lines, with a focus on the α2-6 sialic acid (2-6Sia) modification on glycans, which is associated with cell stemness. Our findings revealed that pancreatic cancer cells exhibited significantly higher levels of 2-6Sia modification, correlating with enhanced reproductive capabilities, whereas cervical cancer cells showed less prevalence of this modification. To accommodate thein vivovariability of 2-6Sia levels, we employed a cell fate simulation algorithm that digitally generates cell populations based on our observed data, simulating cell growth patterns. Subsequently, we constructed a 3D TME model incorporating these deduced cell populations along with specific immune cell landscapes derived from 193 cervical and 172 pancreatic cancer cases. Our analysis suggests that pancreatic cancer cells are less influenced by the immune cell landscape within the TME compared to cervical cancer cells, highlighting that the fate of cancer cells is shaped by both the surrounding immune landscape and the intrinsic characteristics of the cancer cells.
Phenotypic, functional and taxonomic features predict host-pathogen interactions
Authors: Liu-Wei Wang , Kafkas Şenay , Hoehndorf Robert 
Published: December 2018

AbstractMotivationIdentification of host-pathogen interactions (HPIs) can reveal mechanistic insights of infectious diseases for potential treatments and drug discoveries. Current computational methods for the prediction of HPIs often rely on our knowledge on the sequences and functions of pathogen proteins, which is limited for many species, especially for emerging pathogens. Matching the phenotypes elicited by pathogens with phenotypes associated with host proteins might improve the prediction of HPIs.ResultsWe developed an ontology-based machine learning method that predicts potential interaction protein partners for pathogens. Our method exploits information about disease mechanisms through features learned from phenotypic, functional and taxonomic knowledge about pathogens and human proteins. Additionally, by embedding the phenotypic information of the pathogens within a formal representation of pathogen taxonomy, we demonstrate that our model can accurately predict interaction partners for pathogens without known phenotypes, using a combination of their taxonomic relationships with other pathogens and information from ontologies as background knowledge. Our results show that the integration of phenotypic, functional and taxonomic knowledge not only improves the prediction of HPIs, but also enables us to investigate novel pathogens in emerging infectious diseases.Availabilityhttps://github.com/bio-ontology-research-group/hpi-predictContactrobert.hoehndorf@kaust.edu.sa
Recombine supplier-side search via innovation ambidexterity
Authors: Wang Yu , Jia Tao , Chen Jinliang , Sun Hongyi 
Published: December 2018

PurposeThe purpose of this paper is to investigate the individual effects of boundary-spanning search from suppliers (supplier-side search (SS)). It is proposed that SS contributes to innovation ambidexterity (IA) and then business performance (BP). Further, this paper includes buyer–supplier relationships (BSRs) and competitive intensity (CI) as moderators to clarify boundary conditions.Design/methodology/approachAn ordinary least squares regression was employed to test hypotheses, based on 184 sets of data from Hong Kong manufacturing firms. The SPSS version of PROCESS was utilized.FindingsThe results show that IA partially mediates the relationship between SS and BP. Contingently, the direct effect is negatively moderated by BSRs and CI.Research limitations/implicationsThis paper confirms the partial mediating effect of IA on the relationship between SS and BP. Additional mediators, such as organizational innovation and marketing innovation, can be examined in the future.Practical implicationsThis paper contributes to practice by suggesting that suppliers are a rewarding single source for firms to undertake boundary-spanning search. IA plays a significant role in reinforcing the effects of SS on BP and should be implemented with sustaining efforts. BSRs and CI can be detrimental and should be responded to cautiously.Originality/valueThis paper highlights the individual effects of SS on BP. Furthermore, the underlying process and boundary conditions are analyzed. The exploitation-exploration framework is applied throughout the entire study.