bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCL/TAL1 cooperates with Polycomb RYBP-PRC1 to suppress alternative lineages in blood-fated cells
Authors: Chagraoui Hedia , Kristiansen Maiken S. , Ruiz Juan Pablo , Serra-Barros Ana , Richter Johanna , Hall-Ponselé Elisa , Gray Nicki , Waithe Dominic , Clark Kevin , Hublitz Philip , Repapi Emmanouela , Otto Georg , Sopp Paul , Taylor Stephen , Thongjuea Supat , Vyas Paresh , Porcher Catherine 
Published: December 2018

AbstractDuring development, it is unclear if lineage-fated cells derive from multilineage-primed progenitors and whether active mechanisms operate to restrict cell fate. Here we investigate how mesoderm specifies into blood-fated cells. We document temporally restricted co-expression of blood (Scl/Tal1), cardiac (Mesp1) and paraxial (Tbx6) lineage-affiliated transcription factors in single cells, at the onset of blood specification, supporting the existence of common progenitors. At the same time-restricted stage, absence of SCL results in expansion of cardiac/paraxial cell populations and increased cardiac/paraxial gene expression, suggesting active suppression of alternative fates. Indeed, SCL normally activates expression of co-repressor ETO2 and Polycomb-PRC1 subunits (RYBP, PCGF5) and maintains levels of Polycomb-associated histone marks (H2AK119ub/H3K27me3). Genome-wide analyses reveal ETO2 and RYBP co-occupy most SCL target genes, including cardiac/paraxial loci. Reduction of Eto2 or Rybp expression mimics Scl-null cardiac phenotype. Therefore, SCL-mediated transcriptional repression prevents mis-specification of blood-fated cells, establishing active repression as central to fate determination processes.
A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1
Authors: Lam Kwok-ho , Guo Zhuojun , Krez Nadja , Matsui Tsutomu , Perry Kay , Weisemann Jasmin , Rummel Andreas , Bowen Mark E. , Jin Rongsheng 
Published: December 2018

AbstractBotulinum neurotoxin (BoNT) delivers its protease domain across the vesicle membrane to enter the neuronal cytosol upon vesicle acidification. This process is mediated by its translocation domain (HN), but the molecular mechanism underlying membrane insertion of HN remains poorly understood. Here, we report two crystal structures of BoNT/A1 HN that reveal a novel molecular switch (termed BoNT-switch) in HN, where buried α-helices transform into surface-exposed hydrophobic β-hairpins triggered by acidic pH. Locking the BoNT-switch by disulfide trapping inhibited the association of HN with anionic liposomes, blocked channel formation by HN, and reduced the neurotoxicity of BoNT/A1 by up to ~180-fold. Single particle counting studies showed that an acidic environment tends to promote BoNT/A1 self-association on liposomes, which is partly regulated by the BoNT-switch. These findings suggest that the BoNT-switch flips out upon exposure to the acidic endosomal pH, which enables membrane insertion of HN that subsequently leads to LC delivery.
BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment
Authors: D’Alessandro Giuseppina , Whelan Donna Rose , Howard Sean Michael , Vitelli Valerio , Renaudin Xavier , Adamowicz Marek , Iannelli Fabio , Jones-Weinert Corey Winston , Lee MiYoung , Matti Valentina , Lee Wei Ting C. , Morten Michael John , Venkitaraman Ashok Raraakrishnan , Cejka Petr , Rothenberg Eli , d’Adda di Fagagna Fabrizio 
Published: December 2018

AbstractDNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.
Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape
Authors: Chorro Laurent , Suzuki Masako , Chin Shu Shien , Williams Tere M. , Snapp Erik L. , Odagiu Livia , Labrecque Nathalie , Lauvau Grégoire 
Published: December 2018

AbstractFoxp3+CD4+ regulatory T (Treg) cells are essential for preventing fatal autoimmunity and safeguard immune homeostasis in vivo. While expression of the transcription factor Foxp3 and IL-2 signals are both required for the development and function of Treg cells, the commitment to the Treg cell lineage occurs during thymic selection upon T cell receptor (TCR) triggering, and precedes the expression of Foxp3. Whether signals beside TCR contribute to establish Treg cell epigenetic and functional identity is still unknown. Here, using a mouse model with reduced IL-2 signaling, we show that IL-2 regulates the positioning of the pioneer factor SATB1 in CD4+ thymocytes and controls genome wide chromatin accessibility of thymic-derived Treg cells. We also show that Treg cells receiving only low IL-2 signals can suppress endogenous but not WT autoreactive T cell responses in vitro and in vivo. Our findings have broad implications for potential therapeutic strategies to reprogram Treg cells in vivo.
Liriodendron genome sheds light on angiosperm phylogeny and species–pair differentiation
Authors: Chen Jinhui , Hao Zhaodong , Guang Xuanmin , Zhao Chenxi , Wang Pengkai , Xue Liangjiao , Zhu Qihui , Yang Linfeng , Sheng Yu , Zhou Yanwei , Xu Haibin , Xie Hongqing , Long Xiaofei , Zhang Jin , Wang Zhangrong , Shi Mingming , Lu Ye , Liu Siqin , Guan Lanhua , Zhu Qianhua , Yang Liming , Ge Song , Cheng Tielong , Laux Thomas , Gao Qiang , Peng Ye , Liu Na , Yang Sihai , Shi Jisen 
Published: December 2018

AbstractThe genus Liriodendron belongs to the family Magnoliaceae, which resides within the magnoliids, an early diverging lineage of the Mesangiospermae. However, the phylogenetic relationship of magnoliids with eudicots and monocots has not been conclusively resolved and thus remains to be determined1–6. Liriodendron is a relict lineage from the Tertiary with two distinct species—one East Asian (L. chinense (Hemsley) Sargent) and one eastern North American (L. tulipifera Linn)—identified as a vicariad species pair. However, the genetic divergence and evolutionary trajectories of these species remain to be elucidated at the whole-genome level7. Here, we report the first de novo genome assembly of a plant in the Magnoliaceae, L. chinense. Phylogenetic analyses suggest that magnoliids are sister to the clade consisting of eudicots and monocots, with rapid diversification occurring in the common ancestor of these three lineages. Analyses of population genetic structure indicate that L. chinense has diverged into two lineages—the eastern and western groups—in China. While L. tulipifera in North America is genetically positioned between the two L. chinense groups, it is closer to the eastern group. This result is consistent with phenotypic observations that suggest that the eastern and western groups of China may have diverged long ago, possibly before the intercontinental differentiation between L. chinense and L. tulipifera. Genetic diversity analyses show that L. chinense has tenfold higher genetic diversity than L. tulipifera, suggesting that the complicated regions comprising east–west-orientated mountains and the Yangtze river basin (especially near 30° N latitude) in East Asia offered more successful refugia than the south–north-orientated mountain valleys in eastern North America during the Quaternary glacial period.
Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial
Authors: Arabi Yaseen M. , Al-Balwi Mohammed , Hajeer Ali H. , Jawdat Dunia , Sadat Musharaf , Al-Dorzi Hasan M. , Tamim Hani , Afesh Lara , Almashaqbeh Walid , Alkadi Haitham , Alwadaani Deemah , UdayaRaja G. K. , Abdulkareem Ibrahim B. Al , Al-Dawood Abdulaziz 
Published: December 2018

AbstractThe effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.
Screening of 109 neuropeptides on ASICs reveals no direct agonists and dynorphin A, YFMRFamide and endomorphin-1 as modulators
Authors: Vyvers Anna , Schmidt Axel , Wiemuth Dominik , Gründer Stefan 
Published: December 2018

AbstractAcid-sensing ion channels (ASICs) belong to the DEG/ENaC gene family. While ASIC1a, ASIC1b and ASIC3 are activated by extracellular protons, ASIC4 and the closely related bile acid-sensitive ion channel (BASIC or ASIC5) are orphan receptors. Neuropeptides are important modulators of ASICs. Moreover, related DEG/ENaCs are directly activated by neuropeptides, rendering neuropeptides interesting ligands of ASICs. Here, we performed an unbiased screen of 109 short neuropeptides (<20 amino acids) on five homomeric ASICs: ASIC1a, ASIC1b, ASIC3, ASIC4 and BASIC. This screen revealed no direct agonist of any ASIC but three modulators. First, dynorphin A as a modulator of ASIC1a, which increased currents of partially desensitized channels; second, YFMRFamide as a modulator of ASIC1b and ASIC3, which decreased currents of ASIC1b and slowed desensitization of ASIC1b and ASIC3; and, third, endomorphin-1 as a modulator of ASIC3, which also slowed desensitization. With the exception of YFMRFamide, which, however, is not a mammalian neuropeptide, we identified no new modulator of ASICs. In summary, our screen confirmed some known peptide modulators of ASICs but identified no new peptide ligands of ASICs, suggesting that most short peptides acting as ligands of ASICs are already known.
Chemistry of resistivity changes in TiTe/Al2O3 conductive-bridge memories
Authors: Kazar Mendes M. , Martinez E. , Ablett J. M. , Veillerot M. , Gassilloud R. , Bernard M. , Renault O. , Rueff J. P. , Barrett N. 
Published: December 2018

AbstractWe report the chemical phenomena involved in the reverse forming (negative bias on top electrode) and reset of a TaN/TiTe/Al2O3/Ta memory stack. Hard X-ray photoelectron spectroscopy was used to conduct a non-destructive investigation of the critical interfaces between the electrolyte (Al2O3) and the TiTe top and Ta bottom electrodes. During reverse forming, Te accumulates at the TiTe/Al2O3 interface, the TiOx layer between the electrolyte and the electrode is reduced and the TaOx at the interface with Al2O3 is oxidized. These interfacial redox processes are related to an oxygen drift toward the bottom electrode under applied bias, which may favour Te transport into the electrolyte. Thus, the forming processes is related to both Te release and also to the probable migration of oxygen vacancies inside the alumina layer. The opposite phenomena are observed during the reset. TiOx is oxidized near Al2O3 and TaOx is reduced at the Al2O3/Ta interface, following the O2− drift towards the top electrode under positive bias while Te is driven back into the TiTe electrode.
Measuring health facility readiness and its effects on severe malaria outcomes in Uganda
Authors: Ssempiira Julius , Kasirye Ibrahim , Kissa John , Nambuusi Betty , Mukooyo Eddie , Opigo Jimmy , Makumbi Fredrick , Kasasa Simon , Vounatsou Penelope 
Published: December 2018

AbstractThere is paucity of evidence for the role of health service delivery to the malaria decline in Uganda We developed a methodology to quantify health facility readiness and assessed its role on severe malaria outcomes among lower-level facilities (HCIIIs and HCIIs) in the country. Malaria data was extracted from the Health Management Information System (HMIS). General service and malaria-specific readiness indicators were obtained from the 2013 Uganda service delivery indicator survey. Multiple correspondence analysis (MCA) was used to construct a composite facility readiness score based on multiple factorial axes. Geostatistical models assessed the effect of facility readiness on malaria deaths and severe cases. Malaria readiness was achieved in one-quarter of the facilities. The composite readiness score explained 48% and 46% of the variation in the original indicators compared to 23% and 27%, explained by the first axis alone for HCIIIs and HCIIs, respectively. Mortality rate was 64% (IRR = 0.36, 95% BCI: 0.14–0.61) and 68% (IRR = 0.32, 95% BCI: 0.12–0.54) lower in the medium and high compared to low readiness groups, respectively. A composite readiness index is more informative and consistent than the one based on the first MCA factorial axis. In Uganda, higher facility readiness is associated with a reduced risk of severe malaria outcomes.
Evaluation of Immunodiagnostic Tests for Leprosy in Brazil, China and Ethiopia
Authors: van Hooij Anouk , Tjon Kon Fat Elisa M , Batista da Silva Moises , Carvalho Bouth Raquel , Cunha Messias Ana Caroline , Gobbo Angélica Rita , Lema Tsehaynesh , Bobosha Kidist , Li Jinlan , Weng Xiaoman , Salgado Claudio G. , Spencer John S. , Corstjens Paul L. A. M. , Geluk Annemieke 
Published: December 2018

AbstractLeprosy remains persistently endemic in several low- or middle income countries. Transmission is still ongoing as indicated by the unabated rate of leprosy new case detection, illustrating the insufficiency of current prevention methods. Therefore, low-complexity tools suitable for large scale screening efforts to specifically detect M. leprae infection and diagnose disease are required. Previously, we showed that combined detection of cellular and humoral markers, using field-friendly lateral flow assays (LFAs), increased diagnostic potential for detecting leprosy in Bangladesh compared to antibody serology alone. In the current study we assessed the diagnostic performance of similar LFAs in three other geographical settings in Asia, Africa and South-America with different leprosy endemicity. Levels of anti-PGL-I IgM antibody (humoral immunity), IP-10, CCL4 and CRP (cellular immunity) were measured in blood collected from leprosy patients, household contacts and healthy controls from each area. Combined detection of these biomarkers significantly improved the diagnostic potential, particularly for paucibacillary leprosy in all three regions, in line with data obtained in Bangladesh. These data hold promise for the use of low-complexity, multibiomarker LFAs as universal tools for more accurate detection of M. leprae infection and different phenotypes of clinical leprosy.
Temporal and spatial distribution of under-five mortality and factors associated with multiple cases of under-five deaths within a family in the rural area of Khuzestan, Southern Iran
Authors: Anafcheh Tofigh , Yaghoubi Doust Mahmoud , Mojadam Mehdi , Mirkazemi Roksana , Khafaie Morteza Abdullatif 
Published: December 2018

AbstractUnder-five mortality (U5M) is an important indicator of the overall health and development of society. There is a wide gap in U5M among different countries and also within the countries. This study was carried out to assess the prevalence, as well as the socio-demographic, and health-related causes of U5M in the region of study. A cross-sectional study was conducted among all registered cases of U5M in rural areas of Khuzestan province, Iran, during the years 2011 to 2015. To assess the socio-demographic determinants of U5M, the sample surveyed consists of 320 families with at least one under-five death using a multistage random sampling method. Also, this study evaluated the number of variables, which may increase the chance of families to have more than one U5M. U5M was 26 per 1000 live births in 2011, but decreased to 22 per 1000 live births in 2015. With the highest cumulative incidence of 43 in Masjed Soleyman and the lowest of 15 in Dehdez, infant mortality constitutes 76% of all U5M. Prematurity and congenital anomalies were responsible for 46% of all causes of mortality (that is, U5). Maternal age at delivery <18 years or >35 years (OR = 3.5; 95% CI, 1.29–6.22), marriage duration >9 years (1.85, 1.06–3.21), spouse age gap >5 years (2.32, 1.20–4.50), cesarean section (3.85, 1.19–5.74), delivery interval <3 years (2.83, 1.22–5.58), non-Arab ethnicity (2.58, 1.50–4.44), and mother working in agriculture or animal husbandry (3.93, 1.41–6.94) were the most important determinants associated with more than one child death per family. Spatially, there was a great disparity in U5M with different reduction rate during the 5 years of the study. Marriage age, cesarean delivery, delivery interval, and mother field activity were associated with U5M. This may have implications for the preventive health program.
Common Terminology and Acoustic Measures for Human Voice and Birdsong
Authors: Badwal Areen , Poertner JoHanna , Samlan Robin A. , Miller Julie E. 
Published: December 2018

Purpose
The zebra finch is used as a model to study the neural circuitry of auditory-guided human vocal production. The terminology of birdsong production and acoustic analysis, however, differs from human voice production, making it difficult for voice researchers of either species to navigate the literature from the other. The purpose of this research note is to identify common terminology and measures to better compare information across species.

Method
Terminology used in the birdsong literature will be mapped onto terminology used in the human voice production literature. Measures typically used to quantify the percepts of pitch, loudness, and quality will be described. Measures common to the literature in both species will be made from the songs of 3 middle-age birds using Praat and Song Analysis Pro. Two measures, cepstral peak prominence (CPP) and Wiener entropy (WE), will be compared to determine if they provide similar information.

Results
Similarities and differences in terminology and acoustic analyses are presented. A core set of measures including frequency, frequency variability within a syllable, intensity, CPP, and WE are proposed for future studies. CPP and WE are related yet provide unique information about the syllable structure.

Conclusions
Using a core set of measures familiar to both human voice and birdsong researchers, along with both CPP and WE, will allow characterization of similarities and differences among birds. Standard terminology and measures will improve accessibility of the birdsong literature to human voice researchers and vice versa.

Supplemental Material

https://doi.org/10.23641/asha.7438964
Single CCA for IEEE 802.15.4 networks: a cross layer energy model
Authors: Biswas Sankalita , Dhar Roy Sanjay , Chandra Aniruddha 
Published: December 2018

For data frame transmissions in beacon‐enabled mode, an IEEE 802.15.4 node performs two consecutive clear channel assessments (CCAs) to sense the channel after back off. Here, the authors study what would happen if the medium access control (MAC) layer performs only one CCA instead. Although it is apparent that the frame transmission cycle would be shortened with single CCA, it is not straightforward to assess the effect of single CCA on the overall transmission energy. A Markov chain‐based MAC operation model is therefore constructed to analyse single‐CCA‐based MAC layer parameters. A combined physical (PHY) and MAC layer energy model is formulated next. It was found that the single CCA‐based MAC outperforms its standard double CCA‐based counterpart from the energy efficiency perspective.
MALT90 molecular content on high-mass IR-dark clumps
Authors: Saral Gozde , Audard Marc , Wang Yuan 
Published: December 2018

Context. High mass stars form in groups or clusters in dense molecular clumps with sizes of 1 pc and masses of 200 M⊙. Infrared-dark clumps and the individual cores within them with sizes < 0.1 pc and masses < 100 M⊙ are important laboratories for high-mass star formation in order to study the initial conditions.
Aims. We investigate the physical and chemical properties of high-mass clumps in order to better understand the early evolutionary stages and find targets that show star formation signs such as infall motions or outflows.
Methods. We selected the high-mass clumps from ATLASGAL survey that were identified as dark at 8/24 μm wavelengths. We used MALT90 Survey data which provides a molecular line set (HCO+, HNC, HCN, N2H+, H13CO+, HN13C, SiO) to investigate the physical and chemical conditions in early stages of star formation.
Results. Eleven sources have significant SiO detection (over 3σ) which usually indicates outflow activity. Thirteen sources are found with blue profiles in both or either HCO+ and/or HNC lines and clump mass infall rates are estimated to be in the range of 0.2 × 10−3 M⊙ yr−1 − 1.8 × 10−2 M⊙ yr−1. The excitation temperature is obtained as < 24 K for all sources. The column densities for optically thin lines of H13CO+ and HN13C are in the range of 0.4–8.8 (×1012) cm−2, and 0.9–11.9 (×1012) cm−2, respectively, while it is in the range of 0.1–7.5 (×1014) cm−2 for HCO+ and HNC lines. The column densities for N2H+ were ranging between 4.4–275.7 (×1012) cm−2 as expected from cold dense regions. Large line widths of N2H+ might indicate turbulence and large line widths of HCO+, HNC, and SiO indicate outflow activities. Mean optical depths are 20.32, and 23.19 for optically thick HCO+ and HCN lines, and 0.39 and 0.45 for their optically thin isotopologues H13CO+ and HN13C, respectively.
Conclusions. This study reveals the physical and chemical properties of 30 high-mass IR-dark clumps and the interesting targets among them based on their emission line morphology and kinematics.