bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D brain angiogenesis model to reconstitute maturation of functional human blood-brain barrier in vitro
Authors: Lee Somin , Chung Minhwan , Li Jeon Noo 
Published: November 2018

0.AbstractHuman central nervous system (CNS) vasculature in brain expresses a distinctive barrier phenotype, the blood–brain barrier (BBB), which protects the brain against harmful pathogens. Since the BBB contributes to low success rate in CNS pharmacotherapy by restricting drug transportation, the development of an in vitro human BBB model has been in demand. Previous models were unable to fully represent the complex threedimensional (3D) anatomical structure or specific barrier phenotypes of the matured BBB. In this study, we present a physiological 3D microfluidic model of the human BBB that mimics its developmental process including CNS angiogenesis and subsequent maturation in concert with perivascular cells. We used microfluidic hydrogel patterning to precisely and sequentially load perivascular cells into the model, investigate the role of each cell type on BBB phenotypes. We confirmed the necessity of the tri-culture system (brain endothelium with pericytes and astrocytes) to attain the characteristic BBB vascular morphology such as minimized diameter and maximized junction expression. In addition, endothelial-perivascular cell interaction was also critical in reconstituting p-glycoprotein (p-gp), efflux transporter in our model that works as metabolic barrier of BBB and blocks drug to enter CNS. The 3D hydrogel matrix was tuned with hyaluronic acid (HA) to optimize the interaction between endothelial cells and astrocytes. Our in vitro BBB system mimics CNS angiogenesis and characteristic features of BBB. We expect the model will contribute to deeper understanding of neurodegenerative diseases and cost-efficient development of effective CNS medications.
Early divergence of mutational mechanisms drives genetic heterogeneity of fetal tissues
Authors: Kuijk Ewart , Blokzijl Francis , Jager Myrthe , Besselink Nicolle , Boymans Sander , Chuva de Sousa Lopes Susana M. , van Boxtel Ruben , Cuppen Edwin 
Published: November 2018

AbstractA developing human fetus needs to balance rapid cellular expansion with maintaining genomic stability. Here, we accurately quantified and characterized somatic mutation accumulation in fetal tissues by analyzing individual stem cells from human fetal liver and intestine. Fetal mutation rates were ~5-fold higher than in tissue-matched adult stem cells. The mutational landscape of fetal intestinal stem cells resembled that of adult intestinal stem cells, while the mutation spectrum of fetal liver stem cells is distinct from stem cells of the fetal intestine and the adult liver. Our analyses indicate that variation in mutational mechanisms, including oxidative stress and spontaneous deamination of methylated cytosines, contribute to the observed divergence in mutation accumulation patterns and drive genetic mosaicism in humans.One Sentence SummaryLiver and intestinal cells accumulate elevated amounts and diverged types of somatic DNA mutations during early human fetal development
Contribution of Retrotransposition to Developmental Disorders
Authors: Gardner Eugene J. , Prigmore Elena , Gallone Giuseppe , Danecek Petr , Samocha Kaitlin E. , Handsaker Juliet , Gerety Sebastian S. , Ironfield Holly , Short Patrick J. , Sifrim Alejandro , Singh Tarjinder , Chandler Kate E. , Clement Emma , Lachlan Katherine L. , Prescott Katrina , Rosser Elisabeth , FitzPatrick David R. , Firth Helen V. , Hurles Matthew E. ,   on behalf of the Deciphering Developmental Disorders study
Published: November 2018

AbstractMobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.
Boost-HiC : Computational enhancement of long-range contacts in chromosomal contact maps
Authors: Carron L. , Morlot J.B. , V. Matthys , Lesne A. , Mozziconacci J. 
Published: November 2018

AbstractGenome-wide chromosomal contact maps are widely used to uncover the 3D organisation of genomes. They rely on the collection of millions of contacting pairs of genomic loci. Contact frequencies at short range are usually well measured in experiments, while there is a lot of missing information about long-range contacts.We propose to use the sparse information contained in raw contact maps to determine high-confidence contact frequency between all pairs of loci. Our algorithmic procedure, Boost-HiC, enables the detection of Hi-C patterns such as chromosomal compartments at a resolution that would be otherwise only attainable by sequencing a hundred times deeper the experimental Hi-C library. Boost-HiC can also be used to compare contact maps at an improved resolution.Boost-HiC is available at https://github.com/LeopoldC/Boost-HiC
ATR function is indispensable to allow proper mammalian follicle development
Authors: Pacheco Sarai , Garcia-Caldés Montserrat , Roig Ignasi 
Published: November 2018

AbstractMammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.
Genome-wide analysis reveals signatures of selection for gait traits in Yili horse
Authors: Liu Ling-Ling , Fang Chao , Meng Jun , Detilleux Johann , Liu Wu-Jun , Yao Xin-Kui 
Published: November 2018

AbstractHigh quality gaits play an important role in many breeding programs, but the genes of gait were limited at the moment. Here, we present an analysis of genomic selection signatures in 53 individuals from two breeds, using genotype data from the Affymetrix Equine 670K SNP genotyping array. The 11 selection regions of Yili horse were identified using anFSTstatistic and XP-EHH calculated in 200-kb windows across the genome. In total, 50 genes could be found in the 11 regions, and two candidate genes related to locomotory behavior (CLN6, FZD4). The genome of Yili horse and Russian horse were shaped by natural and artificial selection. Our results suggest that gait trait of Yili horse may related to two genes. This is the first time when whole genome array data is utilized to study genomic regions affecting gait in Yili horse breed.
A databank for intracellular electrophysiological mapping of the adult somatosensory cortex
Authors: da Silva Lantyer Angelica , Calcini Niccolò , Bijlsma Ate , Kole Koen , Emmelkamp Melanie , Peeters Manon , Scheenen Wim J. J. , Zeldenrust Fleur , Celikel Tansu 
Published: November 2018

AbstractBackgroundNeurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in the adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.FindingsHere we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9-45 weeks old) from both sexes (females, N=195; males, N=120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N=257; VC, N=46), frozen noise injections (CC, N=104) and triangular voltage sweeps (VC, 10 (N=132), 50 (N=146) and 100 ms (N=152)), from regular spiking (N=169) and fast-spiking neurons (N=66).ConclusionsThe data can be used to systematically study the properties of somatic integration, and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.
Genomic analysis of dingoes identifies genomic regions under reversible selection during domestication and feralization
Authors: Zhang Shao-jie , Wang Guo-Dong , Ma Pengcheng , Zhang Liang-liang , Yin Ting-Ting , Liu Yan-hu , Otecko Newton O. , Wang Meng , Ma Ya-ping , Wang Lu , Mao Bingyu , Savolainen Peter , Zhang Ya-ping 
Published: November 2018

AbstractDingoes(Canis dingo)are wild canids living in Australia. They have lived isolated from both the wild and the domestic ancestor and are a unique model for studying feralization, the process in which a domestic species escapes human control, adapts to the wild, and diverges from the domestic ancestor into a genetically distinct population. Here, we sequenced the genomes of 10 dingoes and 2 New Guinea Singing Dogs, to study the origins and feralization process of the dingo. Phylogenetic and demographic analyses show that dingoes originate from domestic dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia 4300-5000 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identified 99 positively selected genes enriched in starch and fat metabolism pathways, indicating a diet change during feralization of dingoes. Interestingly, we found that 14 genes have shifted allele frequencies compared to dogs but not compared to wolves. This suggests that the selection affecting these genes during domestication of the wolf was reversed in the feralization process. One of these genes,ARHGEF7,may promote the formation of neural spine and synapses in hippocampal neurons. Functional assays showed that an A to G mutation inARHGEF7,located in a transcription factor-binding site, decreases the endogenous expression. This suggests thatARHGEF7may have been under selection for behavioral adaptations related to the transitions in environment both from wild to domestic and from domestic back to wild. Our results indicate that adaptation to domestication and feralization primarily affected different genomic regions, but that some genes, related to neurodevelopment, metabolism and reproduction, may have been reversibly affected in the two processes.
A well-ordered nanoflow LC-MS/MS approach for proteome profiling using 200 cm long micro pillar array columns
Authors: De Beeck Jeff Op , Pauwels Jarne , Van Landuyt Natalie , Jacobs Paul , De Malsche Wim , Desmet Gert , Argentini Andrea , Staes An , Martens Lennart , Impens Francis , Gevaert Kris 
Published: November 2018

ABSTRACTIn bottom-up proteomics, capillaries up to 75 cm long with internal diameters of 50 to 100 µm packed with sub-2-µm C18-functionalized particles are routinely used in combination with high-resolution mass spectrometry. Unlike such conventional liquid chromatography (LC) columns, micro pillar array columns (µPAC™) are fabricated using micromachining technology, resulting in perfectly ordered chromatographic separation beds, leading to a minimized analyte dispersion while column permeability is increased by one order of magnitude. This allows using very long columns (up to 200 cm) at only a fraction of the pressure needed to operate packed bed columns. To validate µPAC™ column performances, different amounts of tryptic digests of HEK293T cell lysates were prepared and separated using a 200 cm µPAC™ column or a 40 cm long conventional column. Using an Orbitrap Elite instrument, on average 25% more proteins were identified with the µPAC™ column. Moreover, the rate at which the peak width increases with gradient time is much lower on the µPAC™ column. For a 10-hour long gradient, average peak widths below 0.5 min were observed, resulting in consistent identification of over 5,000 proteins. Combining long solvent gradients and this new type of LC column, substantial improvements in proteome coverage could be obtained. Finally, we demonstrated high reproducibility and durability of the µPAC™ column. Data are available via ProteomeXchange with identifiers PXD011547 and PXD013235.
Biophysical Studies of Some Bee Products as Radioprotectors
Authors: Hamieda Shimaa F. , Hassan Amal I. , Abdou Mona I. , Khalil Wafaa A. , Abd-El Nour Kamal N. 
Published: November 2018

AbstractThe study had been planned to evaluate some antioxidant ingredients in honey and propolis. Also, a study on ionizing gamma irradiated rats was done to assess these antioxidants as radioprotectors. Bioactive ingredients, such as phenols, flavonoids and trace elements, were explored using FTIR, UV-Vis and AAS spectroscopic techniques. Animals were exposed to fractionated gamma radiation doses. Honey, propolis and their combination were administrated before and during the irradiation period. Serum levels of total protein, albumin and uric acid were estimated. Also, the osmotic fragility of Red Blood Corpuscles (RBCs) membranes and a microscopic examination of blood films were investigated. The analysis demonstrated that the level of phenolic, flavonoid and trace elements are higher in propolis than honey. The levels of total protein and albumin decreased post irradiation while the level of uric acid increased. Likewise, osmotic fragility of RBCs membranes was increased with a sticking forming RBCs aggregation. It had been found that administration of the natural antioxidants induced amelioration in most of the studied parameters. It can be concluded that natural antioxidants produced a modulation against oxidative stress induced by ionizing radiation.Summary StatementAssessment of some antioxidant ingredients in honey and propolis. Also, a study on ionizing gamma irradiated rats was done to assess these antioxidants as radioprotectors.
A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle
Authors: Iso-Touru Terhi , Wurmser Christine , Venhoranta Heli , Hiltpold Maya , Savolainen Tujia , Sironen Anu , Fischer Konrad , Flisikowski Krzysztof , Fries Ruedi , Vicente-Carrillo Alejandro , Alvarez-Rodriguez Manuel , Nagy Szabolcs , Mutikainen Mervi , Peippo Jaana , Taponen Juhani , Sahana Goutam , Guldbrandtsen Bernt , Simonen Henri , Rodriguez-Martinez Heriberto , Andersson Magnus , Pausch Hubert 
Published: November 2018

AbstractBackgroundCattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for many artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected.ResultsBoth bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8,557 fertile bulls although five homozygous haplotype carriers were expected (P=0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5’ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle.ConclusionsOur study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).
Efficient Construction of a Complete Index for Pan-Genomics Read Alignment
Authors: Kuhnle Alan , Mun Taher , Boucher Christina , Gagie Travis , Langmead Ben , Manzini Giovanni 
Published: November 2018

AbstractWhile short read aligners, which predominantly use the FM-index, are able to easily index one or a few human genomes, they do not scale well to indexing databases containing thousands of genomes. To understand why, it helps to examine the main components of the FM-index in more detail, which is a rank data structure over the Burrows-Wheeler Transform (BWT) of the string that will allow us to find the interval in the string’s suffix array (SA) containing pointers to starting positions of occurrences of a given pattern; second, a sample of the SA that — when used with the rank data structure — allows us access the SA. The rank data structure can be kept small even for large genomic databases, by run-length compressing the BWT, but until recently there was no means known to keep the SA sample small without greatly slowing down access to the SA. Now that Gagie et al. (SODA 2018) have defined an SA sample that takes about the same space as the run-length compressed BWT — we have the design for efficient FM-indexes of genomic databases but are faced with the problem of building them. In 2018 we showed how to build the BWT of large genomic databases efficiently (WABI 2018) but the problem of building Gagie et al.’s SA sample efficiently was left open. We compare our approach to state-of-the-art methods for constructing the SA sample, and demonstrate that it is the fastest and most space-efficient method on highly repetitive genomic databases. Lastly, we apply our method for indexing partial and whole human genomes, and show that it improves over Bowtie with respect to both memory and time.AvailabilityWe note that the implementation of our methods can be found here:https://github.com/alshai/r-index.
Evaluation of S1PR1/pSTAT3 and S1PR2/FOXP1 Expression in Aggressive, Mature B Cell Lymphomas
Authors: Al-Kawaaz Mustafa , Sanchez Teresa , Kluk Michael J 
Published: November 2018

AbstractAggressive, mature B-cell lymphomas represent a heterogeneous group of diseases including Burkitt Lymphoma (BL), High Grade B Cell Lymphomas (HGBL) (eg, Double-Hit B cell lymphomas (HGBL-DH: HGBL with MYC and BCL2 and/or BCL6 translocations)), HGBL, Not Otherwise Specified (HGBL, NOS) and Diffuse Large B Cell Lymphoma. The overlapping morphologic and immunohistochemical features of these lymphomas may pose diagnostic challenges in some cases, and a better understanding of potential diagnostic biomarkers and possible therapeutic targets is needed. Sphingosine 1 Phosphate Receptors (S1PR1-5) represent a family of G-protein coupled receptors that bind the sphingolipid (S1P) and influence migration and survival pathways in a variety of cell types, including lymphocytes. S1PRs are emerging as biomarkers in B cell biology and interaction between S1PR pathways and STAT3 or FOXP1 has been reported, especially in DLBCL. Our aim was to extend the understanding of the S1PR1, STAT3 and S1PR2, FOXP1 expression beyond DLBCL, into additional aggressive, mature B cell lymphomas such as BL, HGBL-DH and HGBL,NOS.Herein, we report that S1PR1 and S1PR2 showed different patterns of expression in mantle zones and follicle centers in reactive lymphoid tissue and, among the lymphomas in this study, Burkitt lymphomas showed a unique pattern of expression compared to HGBL and DLBCL. Additionally, we found that S1PR1 and S1PR2 expression was typically mutually exclusive and were expressed in a low proportion of cases (predominantly HGBL involving extranodal sites). Lastly, FOXP1 was expressed in a high proportion of the various case types and pSTAT3 was detected in a significant proportion of HGBL and DLBCL cases. Taken together, these findings provide further evidence that S1PR1, pSTAT3, S1PR2 and FOXP1 play a role in a subset of aggressive mature B cell lymphomas.