bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse Distraction for Treatment of Hydrocephalic Macrocephaly in Late Childhood
Authors: Miller Hannah , Grabb Paul , Lypka Michael 
Published: February 2019

Abstract
Macrocephaly diminishes quality of life for children whose head size inhibits independent mobility and appropriate interaction with caregivers. Cranial reduction is a method of addressing these issues, historically with a high morbidity due most commonly to bleeding and shunt complications. The authors present a 9-year-old girl with holoprosencephaly and severe macrocephaly from progressive hydrocephalus who underwent cranial reduction via reverse distraction osteogenesis, a method to slowly reduce the skull volume. The patient underwent circumferential occipital temporoparietal frontal craniotomy with placement of 4 cranial distractors, followed approximately 1 month later by removal of the distractors and cranioplasty with resorbable fixation devices. The patient demonstrated significant postoperative improvement in head control and interaction in school activities. This is the oldest patient with macrocephaly treated with reverse distraction in the literature to date. The slow contraction of the cranial vault with limited bony surgery at the time of initial reduction provides an additional safety margin, and should be considered in older children presenting with profound macrocephaly.
Reconstruction of Deep Circumflex Iliac Artery Free Flap for Multiple Recurrent Ameloblastoma in Mandible
Authors: Hu YongJie , Cao Rui , Wang ZhongHua , Hong WeiSheng , Zheng ChongYang 
Published: February 2019

Abstract
Ameloblastoma is the most common odontogenic tumor of epithelial origin. These tumors are benign in nature but have a high rate of recurrence and possible malignant development when treated inadequately. However, recurrent ameloblastomas in bone grafts are rare. This article presents a rare case of a multiple recurrent ameloblastoma, with the last recurrence in a nonvascularized free iliac bone graft of the mandible, reconstructed with vascularized deep circumflex iliac artery free flap for the surgical defect. Furthermore, an updated review of the literature on recurrent ameloblastomas affecting the bone graft is provided.
Empowering the annotation and discovery of structured RNAs with scalable and accessible integrative clustering
Authors: Miladi Milad , Sokhoyan Eteri , Houwaart Torsten , Heyne Steffen , Costa Fabrizio , Grüning Björn , Backofen Rolf 
Published: February 2019

ABSTRACTRNA plays essential regulatory roles in all known forms of life. Clustering RNA sequences with common sequence and structure is an essential step towards studying RNA function. With the advent of high-throughput sequencing techniques, experimental and genomic data are expanding to complement the predictive methods. However, the existing methods do not effectively utilize and cope with the immense amount of data becoming available.Here we present GraphClust2, a comprehensive approach for scalable clustering of RNAs based on sequence and structural similarities. GraphClust2 provides an integrative solution by incorporating diverse types of experimental and genomic data in an accessible fashion via the Galaxy framework. We demonstrate that the tasks of clustering and annotation of structured RNAs can be considerably improved, through a scalable methodology that also supports structure probing data. Based on this, we further introduce an off-the-shelf procedure to identify locally conserved structure candidates in long RNAs. In this way, we suggest the presence and the sparsity of phylogenetically conserved local structures in some long non-coding RNAs. Furthermore, we demonstrate the advantage of a scalable clustering for discovering structured motifs under inherent and experimental biases and uncover prominent targets of the double-stranded RNA binding protein Roquin-1 that are evolutionary conserved.
Effects of the secondhand smoking exposure in the early stages of the bone development
Authors: Alves Cristiano Fittipaldi , Carvalho Cesar Alexandre Fabrega , Iemma Antônio Francisco , Neto Francisco Haiter , Caria Paulo Henrique Ferreira 
Published: February 2019

AbstractObjectiveThe objective of this study was to evaluate the effects of the secondhand smoking in the trabecular bone micro-architecture of the mandible of rats, offsprings of passive smoking matrices.Materials and MethodsFifty-five rats,Rattus norvegicus albinus, offsprings of passive smoking and non-passive smoking matrices, were divided into three groups: continuous smoking offsprings (CSO), interrupted smoking offsprings (ISO) and non-smoking offsprings (NSO/control). After the 21st, 42nd, 63rdand 128thdays, the mandibles were analyzed by micro-computer tomography(micro-CT). Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed. The bone volume fraction (BV/TV, bone volume/total volume), the trabecular thickness (Tb.Th), the trabecular spacing (Tb.Sp), the trabecular number (Tb.N) and the structure model index (SMI) were analyzed.ResultsThe BV/TV analysis revealed increase of the average values in the CSO group, at 21stand 42nddays (p=0,0124), tending to decrease related to the mean from the 42ndday. The animals of ISO group did not show significant difference in BV/TV, about the control group (p=0,9751). The results of Tb.Th were different and significant during all the experimental period among the three groups: CSO and control (p<0,0001), ISO and control (p=0,0030) and CSO / ISO (p=0,0020). About Tb.Sp, the differences were not significant among the three groups. About Tb.N, the difference was significant into each group, with increasing values (p<0.0001). The SMI showed significant difference between the CSOs and control, CSO and ISO, both with (p<0,0001). The difference between control and ISO group was not significant (p=0,1253).ConclusionThe passive inhalation of cigarette smoke by the offsprings of smoking matrices had a harmful effect in the micro-archicteture of the trabecular bone of the rats’ mandible in developing. About the ISO groups, the recovery of the micro-archicteture occurred partially.
The autophagic membrane tether ATG2A transfers lipids between membranes
Authors: Maeda Shintaro , Otomo Chinatsu , Otomo Takanori 
Published: February 2019

AbstractAn enigmatic step in de novo formation of the autophagosome membrane compartment is the expansion of the precursor membrane phagophore, which requires the acquisition of lipids to serve as building blocks. Autophagy-related 2 (ATG2), the rod-shaped protein that tethers phosphatidylinositol 3-phosphate (PI3P)-enriched phagophores to the endoplasmic reticulum (ER), is suggested to be essential for phagophore expansion, but the underlying mechanism remains unclear. Here, we demonstrate that human ATG2A is a lipid-transferring protein. ATG2A can extract lipids from membrane vesicles and unload them to other vesicles. Lipid transfer by ATG2A is more efficient between its tethered vesicles than between untethered vesicles. The PI3P effectors WIPI4 and WIPI1 associate ATG2A stably to PI3P-containing vesicles, thereby facilitating ATG2A-mediated tethering and lipid transfer between PI3P-containing vesicles and PI3P-free vesicles. Based on these results, we propose that ATG2-mediated transfer of lipids from the ER to the phagophore enables phagophore expansion.
Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 CNV Mediated Risk for Neuropsychiatric Disorders
Authors: Forsyth Jennifer K. , Nachun Daniel , Gandal Michael J. , Geschwind Daniel H. , Anderson Ariana E. , Coppola Giovanni , Bearden Carrie E. 
Published: February 2019

AbstractBackground22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear.MethodsUsing a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder.ResultsPolygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways.SEPT5, PI4KA, andSNAP29genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, andDGCR8andHIRAare candidate drivers of disease-relevant alterations in gene regulation.ConclusionsThe current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.
MicroRNA-mediated control of developmental lymphangiogenesis
Authors: Jung Hyun Min , Hu Ciara , Fister Alexandra M. , Davis Andrew E. , Castranova Daniel , Pham Van N. , Price Lisa M. , Weinstein Brant M. 
Published: February 2019

ABSTRACTThe post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved miRNA dramatically enriched in lymphatic vs. blood endothelial cells, and we demonstrate that this miRNA plays a critical role during lymphatic development. Suppressing miR-204 leads to loss of lymphatic vessel formation, while overproducing miR-204 in lymphatic vessels accelerates lymphatic vessel formation, suggesting a positive role during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key conserved target for post-transcriptional regulation by miR-204 during lymphangiogenesis. While miR-204 suppression leads to loss of lymphatics, knocking down its target NFATC1 leads to lymphatic hyperplasia, and the loss of lymphatics in miR-204-deficient animals can be rescued by NFATC1 knockdown. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.
An open-source platform to distribute and interpret data from multiplexed assays of variant effect
Authors: Esposito Daniel , Weile Jochen , Shendure Jay , Starita Lea M , Papenfuss Anthony T , Roth Frederick P , Fowler Douglas M , Rubin Alan F 
Published: February 2019

AbstractMultiplex Assays of Variant Effect (MAVEs), such as deep mutational scans and massively parallel reporter assays, test thousands of sequence variants in a single experiment. Despite the importance of MAVE data for basic and clinical research, there is no standard resource for their discovery and distribution. Here we present MaveDB, a public repository for large-scale measurements of sequence variant impact, designed for interoperability with applications to interpret these datasets. We also describe the first of these applications, MaveVis, which retrieves, visualizes, and contextualizes variant effect maps. Together, the database and applications will empower the community to mine these powerful datasets.
A Bayesian Approach for Estimating Branch-Specific Speciation and Extinction Rates
Authors: Höhna Sebastian , Freyman William A. , Nolen Zachary , Huelsenbeck John P. , May Michael R. , Moore Brian R. 
Published: February 2019

AbstractSpecies richness varies considerably among the tree of life which can only be explained by heterogeneous rates of diversification (speciation and extinction). Previous approaches use phylogenetic trees to estimate branch-specific diversification rates. However, all previous approaches disregard diversification-rate shifts on extinct lineages although 99% of species that ever existed are now extinct. Here we describe a lineage-specific birth-death-shift process where lineages, both extant and extinct, may have heterogeneous rates of diversification. To facilitate probability computation we discretize the base distribution on speciation and extinction rates intokrate categories. The fixed number of rate categories allows us to extend the theory of state-dependent speciation and extinction models (e.g.,BiSSE and MuSSE) to compute the probability of an observed phylogeny given the set of speciation and extinction rates. To estimate branch-specific diversification rates, we develop two independent and theoretically equivalent approaches: numerical integration with stochastic character mapping and data-augmentation with reversible-jump Markov chain Monte Carlo sampling. We validate the implementation of the two approaches in RevBayes using simulated data and an empirical example study of primates. In the empirical example, we show that estimates of the number of diversification-rate shifts are, unsurprisingly, very sensitive to the choice of prior distribution. Instead, branch-specific diversification rate estimates are less sensitive to the assumed prior distribution on the number of diversification-rate shifts and consistently infer an increased rate of diversification for Old World Monkeys. Additionally, we observe that as few as 10 diversification-rate categories are sufficient to approximate a continuous base distribution on diversification rates. In conclusion, our implementation of the lineage-specific birth-death-shift model in RevBayes provides biologists with a method to estimate branch-specific diversification rates under a mathematically consistent model.
locBLAST v2.0 - an improved PHP library for embedding standalone NCBI BLAST+ program to an interactive graphical user interface
Authors: Kumar T. Ashok 
Published: February 2019

AbstractBackgroundNCBI BLAST is a most popularly used sequence analysis platform in a broad range of applications. The final release of standalone WWW BLAST server (wwwBLAST v2.2.26) of NCBI was officially released on May 10, 2004, and discontinued its support. Due to the popularity and high demand, the BLAST algorithms were refined with rich features and released as online BLAST, standalone BLAST+, BLAST RESTful service, and cloud BLAST server. locBLAST v2.0 is a lightweight PHP library, designed in preference to WWW BLAST server. It masks command-line BLAST+ programs to a rich graphical user interface (GUI).MethodsThe locBLAST v2.0 library was designed using PHP, CSS, pure JavaScript, and standalone NCBI BLAST+ executables.ResultslocBLAST v2.0 provides an interactive web interface to input query sequences through the web form and provides a graphical report of the sequence alignment result. The graphical overview, tabular summary, and formatted sequence alignment of locBLAST v2.0 result mimic to the native format of online NCBI BLAST result. It allows users to perform both local and online database search.AvailabilityFreely available at https://github.com/AshokHub/locBLAST
Programmable patterns in a DNA-based reaction-diffusion system
Authors: Chen Sifang , Seelig Georg 
Published: February 2019

AbstractBiology offers compelling proof that macroscopic “living materials” can emerge from reactions between diffusing biomolecules. Here, we show that molecular self-organization could be a similarly powerful approach for engineering functional synthetic materials. We introduce a programmable DNA-hydrogel that produces tunable patterns at the centimeter length scale. We generate these patterns by implementing chemical reaction networks through synthetic DNA complexes, embedding the complexes in hydrogel, and triggering with locally applied input DNA strands. We first demonstrate ring pattern formation around a circular input cavity and show that the ring width and intensity can be predictably tuned. Then, we create patterns of increasing complexity, including concentric rings and non-isotropic patterns. Finally, we show “destructive” and “constructive” interference patterns, by combining several ring-forming modules in the gel and triggering them from multiple sources. We further show that computer simulations based on the reaction-diffusion model can predict and inform the programming of target patterns.
CDK1 dependent phosphorylation of hTERT contributes to cancer progression
Authors: Yasukawa Mami , Ando Yoshinari , Yamashita Taro , Matsuda Yoko , Shoji Shisako , Morioka Masaki S. , Kawaji Hideya , Shiozawa Kumiko , Abe Takaya , Yamada Shinji , Kaneko Mika K. , Kato Yukinari , Furuta Yasuhide , Kondo Tadashi , Shirouzu Mikako , Hayashizaki Yoshihide , Kaneko Shuichi , Masutomi Kenkichi 
Published: February 2019

AbstractThe telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses revealed that phosphorylation of hTERT at threonine 249 occurs more frequently in advanced cancers. Using CRISPR/Cas9 genome editing, we introduced substitution mutations at threonine 249 in the endogenous hTERT locus and found that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase activity. Cap Analysis of Gene Expression (CAGE) demonstrated that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomerase independent manner.
Treatment-shortening effect of a novel regimen combining high-dose rifapentine and clofazimine in pathologically distinct mouse models of tuberculosis
Authors: Saini Vikram , Ammerman Nicole C. , Chang Yong Seok , Tasneen Rokeya , Chaisson Richard E. , Jain Sanjay , Nuermberger Eric , Grosset Jacques H. 
Published: February 2019

ABSTRACTHigh-dose rifapentine and clofazimine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.
PhoX – an IMAC-enrichable Crosslinking Reagent
Authors: Steigenberger Barbara A. , Pieters Roland J. , Heck Albert J.R. , Scheltema Richard A. 
Published: February 2019

AbstractChemical crosslinking mass spectrometry is rapidly emerging as a prominent technique to study protein structures. Structural information is obtained by covalently connecting peptides in close proximity by small reagents and identifying the resulting peptide pairs by mass spectrometry. However, sub-stoichiometric reaction efficiencies render routine detection of crosslinked peptides problematic. Here we present a new tri-functional crosslinking reagent, termed PhoX, which is decorated with a stable phosphonic acid handle. This makes the crosslinked peptides amenable to the well-established IMAC enrichment. The handle allows for 300x enrichment efficiency and 97% specificity, dramatically reducing measurement time and improving data quality. We exemplify the approach on various model proteins and protein complexes, e.g. resulting in a structural model of the LRP1/RAP complex. PhoX is also applicable to whole cell lysates. When focusing the database search on ribosomal proteins, our first attempt resulted in 355 crosslinks, out-performing current efforts in less measurement time.
Longitudinal Study on Ocular Manifestations in a Cohort of Patients with Fabry Disease
Authors: Michaud Langis 
Published: February 2019

ABSTRACTPurposeThis study aims to assess the evolution of ocular manifestations in a cohort of Fabry patients.METHODSThis is a prospective observational study conducted from 2013 to 2017 (5 consecutive exams). All subjects underwent a comprehensive ocular examination including oriented case history, refraction, corneal topography, biomechanical corneal properties and pachometry assessments, aberrometry, anterior segment evaluation, double-frequency visual field (FDT), intra-ocular pressure, and ocular fundus. At baseline, 41 subjects enrolled but 9 dropped-out and 4 files were not kept for analysis (missing data). Remaining 28 subjects were classified into: Group 1 -hemizygotes (HMZ), all on enzyme replacement therapy (ERT) (N=10); Group 2 -heterozygotes (HTZ) actively ERT-treated (N=8), and Group 3 -HTZ not treated (N=10).RESULTSThere is a high intra and inter-subjects variability. At baseline, prevalence of the ocular manifestations found is similar to published data: cornea verticillata (89.2%), conjunctival vessels tortuosity (85.7%), corneal haze (67.8%), retinal vessels tortuosity (64.2%), anterior cataract (39.2%) and posterior cataract (28.5%). Prevalence for new elements are found: upper lid vessels toricity (96.4%) and micro-aneurysms (42.8%). At the end, micro-aneurysms (+82%), posterior cataract (+75%) corneal haze (+21%) anterior cataract (+17%) and retinal vessels tortuosities (+4%) evolved in prevalence and severity despite the fact that 68% of the patients were on ERT. Treated heterozygotes evolved more than other groups (p>0.05)CONCLUSIONERT does not halt the clinical evolution of several ocular manifestations. Longer observational time may be required to fully confirm these findings.
Determinants of equity changes in partial acquisitions of Finnish multinationals in foreign markets
Authors: Oguji Nnamdi , Owusu Richard Afriyie , Larimo Jorma 
Published: February 2019

PurposeWhen entering foreign markets, multinationals can acquire part of a foreign firm and can increase or decrease their equity stake over time. However, extant studies have mainly focused on equity stake acquired during initial market entry. The paper aims to discuss this issue.Design/methodology/approachThis study fills this gap by using the Uppsala model to analyze six cases of international acquisitions of Finnish multinationals in global markets.FindingsThe authors found that firms change their equity stake in partially acquired foreign subsidiaries: when they have learned about the host country and businesses of the partially acquired firms, when they have gained target-specific experience, when they build trust and ensure relationship commitment and finally, when they jointly develop and exploit opportunities.Originality/valueThis study is one of the first to apply the Uppsala model to empirically analyze international acquisitions, thus paving the way for behavioral and process-oriented approaches. The study contributes to knowledge of post-entry strategies of multinationals.