bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARTS mediates apoptosis and regeneration of the intestinal stem cell niche
Authors: Koren Elle , Yosefzon Yahav , Ankawa Roi , Soteriou Despina , Jacob Avi , Nevelsky Alexander , Ben-Yosef Rahamim , Bar-Sela Gil , Fuchs Yaron 
Published: October 2018

AbstractStem cells (SCs) play a pivotal role in fueling homeostasis and regeneration. While much focus has been given to self-renewal and differentiation pathways regulating SC fate, little is known regarding the specific mechanisms utilized for their elimination. Here, we report that the pro-apoptotic protein ARTS (a Septin4 isoform) is highly expressed in cells comprising the intestinal SC niche and that its deletion protects Lgr5+ and Paneth cells from undergoing apoptotic cell death. As a result, the Sept4/ARTS−/− crypt displays augmented proliferation and, in culture, generates massive cystic-like organoids due to enhanced Wnt/β-catenin signaling. Importantly, Sept4/ARTS−/− mice exhibit resistance against intestinal damage in a manner dependent upon Lgr5+ SCs. Finally, we show that ARTS interacts with XIAP in intestinal crypt cells and that deletion of XIAP can abrogate Sept4/ARTS−/−-dependent phenotypes. Our results indicate that intestinal SCs utilize specific apoptotic proteins for their elimination, representing a unique target for regenerative medicine.
Genome sequences of two diploid wild relatives of cultivated sweetpotato reveal targets for genetic improvement
Authors: Wu Shan , Lau Kin H. , Cao Qinghe , Hamilton John P. , Sun Honghe , Zhou Chenxi , Eserman Lauren , Gemenet Dorcus C. , Olukolu Bode A. , Wang Haiyan , Crisovan Emily , Godden Grant T. , Jiao Chen , Wang Xin , Kitavi Mercy , Manrique-Carpintero Norma , Vaillancourt Brieanne , Wiegert-Rininger Krystle , Yang Xinsun , Bao Kan , Schaff Jennifer , Kreuze Jan , Gruneberg Wolfgang , Khan Awais , Ghislain Marc , Ma Daifu , Jiang Jiming , Mwanga Robert O. M. , Leebens-Mack Jim , Coin Lachlan J. M. , Yencho G. Craig , Buell C. Robin , Fei Zhangjun 
Published: October 2018

AbstractSweetpotato [Ipomoea batatas (L.) Lam.] is a globally important staple food crop, especially for sub-Saharan Africa. Agronomic improvement of sweetpotato has lagged behind other major food crops due to a lack of genomic and genetic resources and inherent challenges in breeding a heterozygous, clonally propagated polyploid. Here, we report the genome sequences of its two diploid relatives, I. trifida and I. triloba, and show that these high-quality genome assemblies are robust references for hexaploid sweetpotato. Comparative and phylogenetic analyses reveal insights into the ancient whole-genome triplication history of Ipomoea and evolutionary relationships within the Batatas complex. Using resequencing data from 16 genotypes widely used in African breeding programs, genes and alleles associated with carotenoid biosynthesis in storage roots are identified, which may enable efficient breeding of varieties with high provitamin A content. These resources will facilitate genome-enabled breeding in this important food security crop.
Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA
Authors: Chen Lechuang , Feng Zhimin , Yue Hong , Bazdar Douglas , Mbonye Uri , Zender Chad , Harding Clifford V. , Bruggeman Leslie , Karn Jonathan , Sieg Scott F. , Wang Bingcheng , Jin Ge 
Published: October 2018

AbstractPeople living with HIV/AIDS on antiretroviral therapy have increased risk of non-AIDS-defining cancers (NADCs). However, the underlying mechanism for development and progression of certain NADCs remains obscure. Here we show that exosomes released from HIV-infected T cells and those purified from blood of HIV-positive patients stimulate proliferation, migration and invasion of oral/oropharyngeal and lung cancer cells. The HIV transactivation response (TAR) element RNA in HIV-infected T-cell exosomes is responsible for promoting cancer cell proliferation and inducing expression of proto-oncogenes and Toll-like receptor 3 (TLR3)-inducible genes. These effects depend on the loop/bulge region of the molecule. HIV-infected T-cell exosomes rapidly enter recipient cells through epidermal growth factor receptor (EGFR) and stimulate ERK1/2 phosphorylation via the EGFR/TLR3 axis. Thus, our findings indicate that TAR RNA-containing exosomes from HIV-infected T cells promote growth and progression of particular NADCs through activation of the ERK cascade in an EGFR/TLR3-dependent manner.
Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice
Authors: Matsui Sho , Sasaki Tsutomu , Kohno Daisuke , Yaku Keisuke , Inutsuka Ayumu , Yokota-Hashimoto Hiromi , Kikuchi Osamu , Suga Takayoshi , Kobayashi Masaki , Yamanaka Akihiro , Harada Akihiro , Nakagawa Takashi , Onaka Tatsushi , Kitamura Tadahiro 
Published: October 2018

AbstractDiet affects health through ingested calories and macronutrients, and macronutrient balance affects health span. The mechanisms regulating macronutrient-based diet choices are poorly understood. Previous studies had shown that NAD-dependent deacetylase sirtuin-1 (SIRT1) in part influences the health-promoting effects of caloric restriction by boosting fat use in peripheral tissues. Here, we show that neuronal SIRT1 shifts diet choice from sucrose to fat in mice, matching the peripheral metabolic shift. SIRT1-mediated suppression of simple sugar preference requires oxytocin signalling, and SIRT1 in oxytocin neurons drives this effect. The hepatokine FGF21 acts as an endocrine signal to oxytocin neurons, promoting neuronal activation and Oxt transcription and suppressing the simple sugar preference. SIRT1 promotes FGF21 signalling in oxytocin neurons and stimulates Oxt transcription through NRF2. Thus, neuronal SIRT1 contributes to the homeostatic regulation of macronutrient-based diet selection in mice.
Sex specific function of epithelial STAT3 signaling in pathogenesis of K-ras mutant lung cancer
Authors: Caetano Mauricio S. , Hassane Maya , Van Hieu T. , Bugarin Emmanuel , Cumpian Amber M. , McDowell Christina L. , Cavazos Carolina Gonzalez , Zhang Huiyuan , Deng Shanshan , Diao Lixia , Wang Jing , Evans Scott E. , Behrens Carmen , Wistuba Ignacio I. , Fuqua Susan A. W. , Lin Huang , Stabile Laura P. , Watowich Stephanie S. , Kadara Humam , Moghaddam Seyed Javad 
Published: October 2018

AbstractLung adenocarcinomas (LUADs) with mutations in the K-ras oncogene display dismal prognosis. Proinflammatory and immunomodulatory events that drive development of K-ras mutant LUAD are poorly understood. Here, we develop a lung epithelial specific K-ras mutant/Stat3 conditional knockout (LR/Stat3Δ/Δ) mouse model. Epithelial Stat3 deletion results in intriguing sex-associated discrepancies; K-ras mutant tumors are decreased in female LR/Stat3Δ/Δ mice whereas tumor burdens are increased in males. RNA-sequencing and tumor microenvironment (TME) analysis demonstrate increased anti-tumor immune responses following Stat3 deletion in females and, conversely, elevated pro-tumor immune pathways in males. While IL-6 blockade in male LR/Stat3Δ/Δ mice reduces lung tumorigenesis, inhibition of estrogen receptor signaling in female mice augments K-ras mutant oncogenesis and reprograms lung TME toward a pro-tumor phenotype. Our data underscore a critical sex-specific role for epithelial Stat3 signaling in K-ras mutant LUAD, thus paving the way for developing personalized (e.g. sex-based) immunotherapeutic strategies for this fatal disease.
Baleen whale cortisol levels reveal a physiological response to 20th century whaling
Authors: Trumble Stephen J. , Norman Stephanie A. , Crain Danielle D. , Mansouri Farzaneh , Winfield Zach C. , Sabin Richard , Potter Charles W. , Gabriele Christine M. , Usenko Sascha 
Published: October 2018

AbstractOne of the most important challenges researchers and managers confront in conservation ecology is predicting a population’s response to sub-lethal stressors. Such predictions have been particularly elusive when assessing responses of large marine mammals to past anthropogenic pressures. Recently developed techniques involving baleen whale earplugs combine age estimates with cortisol measurements to assess spatial and temporal stress/stressor relationships. Here we show a relationship between baseline-corrected cortisol levels and corresponding whaling counts of fin, humpback, and blue whales in the Northern Hemisphere spanning the 20th century. We also model the impact of alternative demographic and environmental factors and determine that increased anomalies of sea surface temperature over a 46-year mean (1970–2016) were positively associated with cortisol levels. While industrial whaling can deplete populations by direct harvest, our data underscore a widespread stress response in baleen whales that is peripheral to whaling activities or associated with other anthropogenic change.
Tissue-resident memory T cells populate the human brain
Authors: Smolders Joost , Heutinck Kirstin M. , Fransen Nina L. , Remmerswaal Ester B. M. , Hombrink Pleun , ten Berge Ineke J. M. , van Lier René A. W. , Huitinga Inge , Hamann Jörg 
Published: October 2018

AbstractMost tissues are populated by tissue-resident memory T cells (TRM cells), which are adapted to their niche and appear to be indispensable for local protection against pathogens. Here we show that human white matter-derived brain CD8+ T cells can be subsetted into CD103−CD69+ and CD103+CD69+ T cells both with a phenotypic and transcription factor profile consistent with TRM cells. Specifically, CD103 expression in brain CD8+ T cells correlates with reduced expression of differentiation markers, increased expression of tissue-homing chemokine receptors, intermediate and low expression of the transcription factors T-bet and eomes, increased expression of PD-1 and CTLA-4, and low expression of cytolytic enzymes with preserved polyfunctionality upon activation. Brain CD4+ T cells also display TRM cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by TRM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish
Authors: Abdul-Wajid Sarah , Demarest Bradley L. , Yost H. Joseph 
Published: October 2018

AbstractNeural crest cells migrate to the embryonic heart and transform into a small number of cardiomyocytes, but their functions in the developing and adult heart are unknown. Here, we show that neural crest derived cardiomyocytes (NC-Cms) in the zebrafish ventricle express Notch ligand jag2b, are adjacent to Notch responding cells, and persist throughout life. Genetic ablation of NC-Cms during embryogenesis results in diminished jag2b, altered Notch signaling and aberrant trabeculation patterns, but is not detrimental to early heart function or survival to adulthood. However, embryonic NC-Cm ablation results in adult fish that show severe hypertrophic cardiomyopathy (HCM), altered cardiomyocyte size, diminished adult heart capacity and heart failure in cardiac stress tests. Adult jag2b mutants have similar cardiomyopathy. Thus, we identify a cardiomyocyte population and genetic pathway that are required to prevent adult onset HCM and provide a zebrafish model of adult-onset HCM and heart failure.
Generalized Hartmann-Shack array of dielectric metalens sub-arrays for polarimetric beam profiling
Authors: Yang Zhenyu , Wang Zhaokun , Wang Yuxi , Feng Xing , Zhao Ming , Wan Zhujun , Zhu Liangqiu , Liu Jun , Huang Yi , Xia Jinsong , Wegener Martin 
Published: October 2018

AbstractTo define and characterize optical systems, obtaining the amplitude, phase, and polarization profile of optical beams is of utmost importance. Traditional polarimetry is well established to characterize the polarization state. Recently, metasurfaces have successfully been introduced as compact optical components. Here, we take the metasurface concept to the system level by realizing arrays of metalenses, allowing the determination of the polarization profile of an optical beam. We use silicon-based metalenses with a numerical aperture of 0.32 and a mean measured focusing efficiency in transmission mode of 28% at a wavelength of 1550 nm. Our system is extremely compact and allows for real-time beam diagnostics by inspecting the foci amplitudes. By further analyzing the foci displacements in the spirit of a Hartmann-Shack wavefront sensor, we can simultaneously detect phase-gradient profiles. As application examples, we diagnose the profiles of a radially polarized beam, an azimuthally polarized beam, and of a vortex beam.
NuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells
Authors: Kloet Susan L. , Karemaker Ino D. , van Voorthuijsen Lisa , Lindeboom Rik G. H. , Baltissen Marijke P. , Edupuganti Raghu R. , Poramba-Liyanage Deepani W. , Jansen Pascal W. T. C. , Vermeulen Michiel 
Published: October 2018

AbstractThe nucleosome remodeling and deacetylase (NuRD) complex plays an important role in gene expression regulation, stem cell self-renewal, and lineage commitment. However, little is known about the dynamics of NuRD during cellular differentiation. Here, we study these dynamics using genome-wide profiling and quantitative interaction proteomics in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We find that the genomic targets of NuRD are highly dynamic during differentiation, with most binding occurring at cell-type specific promoters and enhancers. We identify ZFP296 as an ESC-specific NuRD interactor that also interacts with the SIN3A complex. ChIP-sequencing in Zfp296 knockout (KO) ESCs reveals decreased NuRD binding both genome-wide and at ZFP296 binding sites, although this has little effect on the transcriptome. Nevertheless, Zfp296 KO ESCs exhibit delayed induction of lineage-specific markers upon differentiation to embryoid bodies. In summary, we identify an ESC-specific NuRD-interacting protein which regulates genome-wide NuRD binding and cellular differentiation.
Global-scale control of extensional tectonics on CO2 earth degassing
Authors: Tamburello Giancarlo , Pondrelli Silvia , Chiodini Giovanni , Rouwet Dmitri 
Published: October 2018

AbstractEarth degassing of CO2-rich fluids has been proven to contribute significantly to the global carbon budget. The presence of ubiquitous outgassing reveals some degree of permeability of the crust that often coincides with seismically active zones. In this study, we took advantage of the most recent global geological datasets to better understand earth degassing and how it correlates with tectonic regimes. Here we use an ad hoc point pattern analysis to show that there is a spatial correlation between CO2discharges and the presence of active fault systems, in particular with those characterized by a normal slip type. Seismic data demonstrate the existence of a positive spatial correlation between gas discharges and extensional tectonic regimes and confirms that such processes would play a key role in creating pathways for the rising gases at micro- and macro-scales, increasing the rock permeability and connecting the deep crust to the earth surface.
Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity
Authors: Chen Xingqi , Litzenburger Ulrike M. , Wei Yuning , Schep Alicia N. , LaGory Edward L. , Choudhry Hani , Giaccia Amato J. , Greenleaf William J. , Chang Howard Y. 
Published: October 2018

AbstractHere we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.
Effective Three-Body Interactions in Jaynes-Cummings-Hubbard Systems
Authors: Prasad Srivatsa B. , Martin Andrew M. 
Published: October 2018

AbstractA generalisation of the Jaynes-Cummings-Hubbard model for coupled-cavity arrays is introduced, where the embedded two-level system in each cavity is replaced by a Ξ-type three-level system. We demonstrate that the resulting effective polariton-polariton interactions at each site are both two-body and three-body. By tuning the ratio of the two transition dipole matrix elements, we show that the strength and sign of the two-body interaction can be controlled whilst maintaining a three-body repulsion. We then proceed to demonstrate how different two-body and three-body interactions alter the mean field superfluid-Mott insulator phase diagram, with the possible emergence of a pair superfluid phase in the two-body attractive regime.
Genotyping-by-sequencing supports a genetic basis for wing reduction in an alpine New Zealand stonefly
Authors: Veale Andrew J. , Foster Brodie J. , Dearden Peter K. , Waters Jonathan M. 
Published: October 2018

AbstractWing polymorphism is a prominent feature of numerous insect groups, but the genomic basis for this diversity remains poorly understood. Wing reduction is a commonly observed trait in many species of stoneflies, particularly in cold or alpine environments. The widespread New Zealand stoneflyZelandoperla fenestrataspecies group (Z.fenestrata,Z.tillyardi,Z.pennulata) contains populations ranging from fully winged (macropterous) to vestigial-winged (micropterous), with the latter phenotype typically associated with high altitudes. The presence of flightless forms on numerous mountain ranges, separated by lowland fully winged populations, suggests wing reduction has occurred multiple times. We use Genotyping by Sequencing (GBS) to test for genetic differentiation between fully winged (n = 62) and vestigial-winged (n = 34) individuals, sampled from a sympatric population of distinct wing morphotypes, to test for a genetic basis for wing morphology. While we found no population genetic differentiation between these two morphotypes across 6,843 SNP loci, we did detect several outlier loci that strongly differentiated morphotypes across independent tests. These findings indicate that small regions of the genome are likely to be highly differentiated between morphotypes, suggesting a genetic basis for wing reduction. Our results provide a clear basis for ongoing genomic analysis to elucidate critical regulatory pathways for wing development in Pterygota.
Fast, Cost-effective and Energy Efficient Mercury Removal-Recycling Technology
Authors: Ganguly Mainak , Dib Simon , Ariya Parisa A. 
Published: October 2018

AbstractWe herein present a novel and sustainable technology for mercury recycling, with the maximum observed uptake capacity. Facile synthesis of the most efficient (~1.9 gg−1) nano-trap, made of montmorillonite-Fe-iron oxides, was performed to instantaneously remove mercury(II) ions from water. Elemental Hg was recovered from the adduct, by employing Fe granules, at ambient conditions. Varied pHs and elevated temperatures further enhanced this already highly efficient recycling process. The reduction of Hg(II) to Hg(I) by the nano trap and Hg(I) to Hg(0) by Fe granules are the main driving forces behind the recycling process. Facile sustainable recycling of the nano-trap and Fe granules require no additional energy. We have further developed a recyclable model for Hg nano-trap, which is inexpensive (<$5 CAD), and can remove mercury in a few seconds. This technology has multiple applications, including in the communities exposed to mercury contamination.
Measurement of mean subcutaneous fat thickness: eight standardised ultrasound sites compared to 216 randomly selected sites
Authors: Störchle Paul , Müller Wolfram , Sengeis Marietta , Lackner Sonja , Holasek Sandra , Fürhapter-Rieger Alfred 
Published: October 2018

AbstractUltrasound (US) provides the most accurate technique for thickness measurements of subcutaneous adipose tissue (SAT) layers. This US method was recently standardised using eight sites to capture SAT patterning and allows distinguishing between fat and embedded fibrous structures. These eight sites chosen for fat patterning studies do not represent the mean SAT thickness measured all over the body that is necessary for determining subcutaneous fat mass. This was obtained by SAT measurements at 216 sites distributed randomly all over the body. Ten participants with BMI below 28.5kgm−2and SAT means (from eight sites) ranging from 3 mm to 10 mm were selected. The means from eight sites overestimated the means obtained from 216 sites (i.e. 2160 US measurements in the ten participants); the calibration factor of 0.65 corrects this; standard deviation (SD) was 0.05, i.e. 8%. The SD of the calibration factor transforms linearly when estimating the error range of the whole body’s SAT volume (body surface area times the calibrated mean SAT thickness). The SAT masses ranged from 3.2 to 12.4 kg in this group. The standard deviations resulting from solely the calibration factor uncertainty were ±0.3 and ±1.0 kg, respectively. For these examples, the SAT percentages were 4.9(±0.4)% and 13.3(±1.0)%.
X-linked ADGRG2 mutation and obstructive azoospermia in a large Pakistani family
Authors: Khan Muhammad Jaseem , Pollock Nijole , Jiang Huaiyang , Castro Carlos , Nazli Rubina , Ahmed Jawad , Basit Sulman , Rajkovic Aleksandar , Yatsenko Alexander N. 
Published: October 2018

AbstractWe performed whole exome sequencing to identify an unknown genetic cause of azoospermia and male infertility in a large Pakistani family. Three infertile males were subjected to semen analysis, hormone testing, testicular histology, ultrasonography, karyotyping, Y-chromosome microdeletion and CFTR testing. The clinical testing suggested a diagnosis of obstructive azoospermia (OA). To identify the cause, we performed whole exome sequencing (WES) for 2 infertile brothers and 2 fertile family members. For segregation analysis and variant confirmation, we performed Sanger sequencing. WES data analysis of the family revealed segregated variants in 3 candidate genes. We considered novel nonsense variant c.2440C > T(p.Arg814*) in X-linked gene ADGRG2 as biologically most plausible. It is predicted to truncate the protein by 204 amino acids (aa) at a key transmembrane domain. Adgrg2-knockout male mice show sperm loss due to obstructive fluid stasis, while ADGRG2 mutations cause OA in the infertile male patients. Our analysis of testicular histology reveals secondary severe reduction of spermatogenesis, consistent with human and knockout mouse phenotypes. The ADGRG2 nonsense mutation is absent in the largest population databases, ExAC and gnomAD. Analysis of the novel nonsense mutation in extended family members confirmed co-segregation of the mutation with OA in all affected males. The likely pathogenic nature of the mutation is supported by its truncation effect on the transmembrane domain and distinctive ultrasound results. The study demonstrates effectiveness of WES in discovering a genetic cause of azoospermia.