bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-Fucose and Fringe-modified NOTCH1 extracellular domain fragments as decoys to release niche-lodged hematopoietic progenitor cells
Authors: Yu Shuiliang , Wang Weihuan , Albakri Marwah , Yu Xiaoxing , Majihail Gurnoor , Lim Seunghwan , Lopilato Rachel K , Ito Atsuko , Letterio John , Haltiwanger Robert S , Zhou Lan 
Published: December 2020

Abstract
Successful hematopoietic progenitor cell (HPC) transplant therapy is improved by mobilizing HPCs from the bone marrow niche in donors. Notch receptor–ligand interactions are known to retain HPCs in the bone marrow, and neutralizing antibodies against Notch ligands, Jagged-1 or Delta-like ligand (DLL4), or NOTCH2 receptor potentiates HPC mobilization. Notch–ligand interactions are dependent on posttranslational modification of Notch receptors with O-fucose and are modulated by Fringe-mediated extension of O-fucose moieties. We previously reported that O-fucosylglycans on Notch are required for Notch receptor–ligand engagement controlling hematopoietic stem cell quiescence and retention in the marrow niche. Here, we generated recombinant fragments of NOTCH1 or NOTCH2 extracellular domain carrying the core ligand-binding regions (EGF11–13) either as unmodified forms or as O-fucosylglycan-modified forms. We found that the addition of O-fucose monosaccharide or the Fringe-extended forms of O-fucose to EGF11–13 showed substantial increases in binding to DLL4. Furthermore, the O-fucose and Fringe-extended NOTCH1 EGF11–13 protein displayed much stronger binding to DLL4 than the NOTCH2 counterpart. When assessed in an in vitro 3D osteoblastic niche model, we showed that the Fringe-extended NOTCH1 EGF11–13 fragment effectively released lodged HPC cells with a higher potency than the NOTCH2 blocking antibody. We concluded that O-fucose and Fringe-modified NOTCH1 EGF11–13 protein can be utilized as effective decoys for stem cell niche localized ligands to potentiate HPC egress and improve HPC collection for hematopoietic cell therapy.
Cross-talk between mitochondrial function, growth, and stress signalling pathways in plants
Authors: Welchen Elina , Canal María Victoria , Gras Diana E , Gonzalez Daniel H 
Published: December 2020

Abstract
Plant mitochondria harbour complex metabolic routes that are interconnected with those of other cell compartments, and changes in mitochondrial function remotely influence processes in different parts of the cell. This implies the existence of signals that convey information about mitochondrial function to the rest of the cell. Increasing evidence indicates that metabolic and redox signals are important for this process, but changes in ion fluxes, protein relocalization, and physical contacts with other organelles are probably also involved. Besides possible direct effects of these signalling molecules on cellular functions, changes in mitochondrial physiology also affect the activity of different signalling pathways that modulate plant growth and stress responses. As a consequence, mitochondria influence the responses to internal and external factors that modify the activity of these pathways and associated biological processes. Acting through the activity of hormonal signalling pathways, mitochondria may also exert remote control over distant organs or plant tissues. In addition, an intimate cross-talk of mitochondria with energy signalling pathways, such as those represented by TARGET OF RAPAMYCIN and SUCROSE NON-FERMENTING1-RELATED PROTEIN KINASE 1, can be envisaged. This review discusses available evidence on the role of mitochondria in shaping plant growth and stress responses through various signalling pathways.
Asteroseismology of luminous red giants with Kepler – II. Dependence of mass-loss on pulsations and radiation
Authors: Yu Jie , Hekker Saskia , Bedding Timothy R , Stello Dennis , Huber Daniel , Gizon Laurent , Khanna Shourya , Bi Shaolan 
Published: December 2020

ABSTRACT
Mass-loss by red giants is an important process to understand the final stages of stellar evolution and the chemical enrichment of the interstellar medium. Mass-loss rates are thought to be controlled by pulsation-enhanced dust-driven outflows. Here, we investigate the relationships between mass-loss, pulsations, and radiation, using 3213 luminous Kepler red giants and 13 5000 ASAS–SN semiregulars and Miras. Mass-loss rates are traced by infrared colours using 2MASS and Wide-field Infrared Survey Explorer(WISE) and by observed-to-model WISE fluxes, and are also estimated using dust mass-loss rates from literature assuming a typical gas-to-dust mass ratio of 400. To specify the pulsations, we extract the period and height of the highest peak in the power spectrum of oscillation. Absolute magnitudes are obtained from the 2MASS Ks band and the Gaia DR2 parallaxes. Our results follow. (i) Substantial mass-loss sets in at pulsation periods above ∼60 and ∼100 d, corresponding to Asymptotic-Giant-Branch stars at the base of the period-luminosity sequences C′ and C. (ii) The mass-loss rate starts to rapidly increase in semiregulars for which the luminosity is just above the red-giant-branch tip and gradually plateaus to a level similar to that of Miras. (iii) The mass-loss rates in Miras do not depend on luminosity, consistent with pulsation-enhanced dust-driven winds. (iv) The accumulated mass-loss on the red giant branch consistent with asteroseismic predictions reduces the masses of red-clump stars by 6.3 per cent, less than the typical uncertainty on their asteroseismic masses. Thus mass-loss is currently not a limitation of stellar age estimates for galactic archaeology studies.
Fast and Robust Identity-by-Descent Inference with the Templated Positional Burrows–Wheeler Transform
Authors: Freyman William A , McManus Kimberly F , Shringarpure Suyash S , Jewett Ethan M , Bryc Katarzyna ,   The 23 and Me Research Team, Auton Adam 
Published: December 2020

Abstract
Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows–Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors, we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally, we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale data sets with millions of samples. Furthermore, we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis, exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for noncommercial use in the code repository (https://github.com/23andMe/phasedibd, last accessed January 11, 2021).
Evidence for multi-copy Mega-NUMTsin the human genome
Authors: Lutz-Bonengel Sabine , Niederstätter Harald , Naue Jana , Koziel Rafal , Yang Fengtang , Sänger Timo , Huber Gabriela , Berger Cordula , Pflugradt René , Strobl Christina , Xavier Catarina , Volleth Marianne , Weiß Sandra Carina , Irwin Jodi A , Romsos Erica L , Vallone Peter M , Ratzinger Gudrun , Schmuth Matthias , Jansen-Dürr Pidder , Liehr Thomas , Lichter Peter , Parsons Thomas J , Pollak Stefan , Parson Walther 
Published: December 2020

AbstractThe maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.
The MDM2 inducible promoter folds into four-tetrad antiparallel G-quadruplexes targetable to fight malignant liposarcoma
Authors: Lago Sara , Nadai Matteo , Ruggiero Emanuela , Tassinari Martina , Marušič Maja , Tosoni Beatrice , Frasson Ilaria , Cernilogar Filippo M , Pirota Valentina , Doria Filippo , Plavec Janez , Schotta Gunnar , Richter Sara N 
Published: December 2020

Abstract
Well-differentiated liposarcoma (WDLPS) is a malignant neoplasia hard to diagnose and treat. Its main molecular signature is amplification of the MDM2-containing genomic region. The MDM2 oncogene is the master regulator of p53: its overexpression enhances p53 degradation and inhibits apoptosis, leading to the tumoral phenotype. Here, we show that the MDM2 inducible promoter G-rich region folds into stable G-quadruplexes both in vitro and in vivo and it is specifically recognized by cellular helicases. Cell treatment with G-quadruplex-ligands reduces MDM2 expression and p53 degradation, thus stimulating cancer cell cycle arrest and apoptosis. Structural characterization of the MDM2 G-quadruplex revealed an extraordinarily stable, unique four-tetrad antiparallel dynamic conformation, amenable to selective targeting. These data indicate the feasibility of an out-of-the-box G-quadruplex-targeting approach to defeat WDLPS and all tumours where restoration of wild-type p53 is sought. They also point to G-quadruplex-dependent genomic instability as possible cause of MDM2 expansion and WDLPS tumorigenesis.
Proportionate mortality study of unionized maintenance of way railroad workers
Authors: Goldsmith D F , Barlet G 
Published: December 2020

Abstract

Background
Railroad maintenance of way (MOW) workers are exposed to many workplace hazards, including diesel fuel and exhaust, ballast (silica) dust, asbestos, solvents, herbicides, welding fumes, heavy rolling equipment, vibration and extreme weather.

Aims
Due to the number of excess deaths we found in a companion standardized mortality ratio (SMR) study for union members &lt;65 years, we hypothesized that these workers may have elevated mortality risks among all ages for many chronic conditions.

Methods
Proportionate mortality ratios (PMRs) were calculated for 37 661 male MOW workers ages 20 and older who were members of the Brotherhood of Maintenance of Way Employes Division (BMWED). A data set was submitted to the National Death Index (NDI) to identify decedents and to determine cause of death for workers who died between 1979 and 2014. The CDC WONDER database was used to determine expected mortality for US males.

Results
For certain diseases and cancers the SMR and PMR findings have parallel mortality excesses. Examples include septicaemia and anaemia; diabetes; chronic obstructive pulmonary disease (COPD); nephritis; and transportation accidents. Among cancers, we found excess oesophageal, stomach, colorectal, lung, prostate, kidney and in situ cancers. Two excess SMR findings were not replicated in the PMR assessment—Alzheimer’s and Parkinson’s disease.

Conclusions
The PMR findings suggest that some of the mortality excesses from the SMR study are elevated, which adds support to their being consistently raised among BMWED members. The shared excess causes of death in the PMR and SMR studies should be focused on for future prevention and surveillance activities.
Family Policy as a Power Source of Political Stability: The Experience of Kazakhstan
Authors: Iskakova Zhuldyzay , Kalashnikova Natalya , Onychko Marina , Salikzhanov Rinat , Smagambet Bayan , Otar Elmira , Abetova Zeinep 
Published: December 2020

Abstract
This article is based on an analysis of the results of a survey conducted among 106 experts in the field of family policy in Kazakhstan in March 2020. The study results provided an expert assessment of family policy effectiveness in Kazakhstan and civil society’s role in it. The results show that experts assess the effectiveness of the civil sector in implementing the national family policy above the state: the level of efficiency is two times higher, and the level of knowledge and competencies is three times higher. In this regard, the government should interact more intensively with non-governmental organizations.
Phylogenomics, Origin, and Diversification of Anthozoans (Phylum Cnidaria)
Authors: McFadden Catherine S , Quattrini Andrea M , Brugler Mercer R , Cowman Peter F , Dueñas Luisa F , Kitahara Marcelo V , Paz-García David A , Reimer James D , Rodríguez Estefanía 
Published: December 2020

Abstract
Anthozoan cnidarians (corals and sea anemones) include some of the world’s most important foundation species, capable of building massive reef complexes that support entire ecosystems. Although previous molecular phylogenetic analyses have revealed widespread homoplasy of the morphological characters traditionally used to define orders and families of anthozoans, analyses using mitochondrial genes or rDNA have failed to resolve many key nodes in the phylogeny. With a fully resolved, time-calibrated phylogeny for 234 species constructed from hundreds of ultraconserved elements and exon loci, we explore the evolutionary origins of the major clades of Anthozoa and some of their salient morphological features. The phylogeny supports reciprocally monophyletic Hexacorallia and Octocorallia, with Ceriantharia as the earliest diverging hexacorals; two reciprocally monophyletic clades of Octocorallia; and monophyly of all hexacoral orders with the exception of the enigmatic sea anemone Relicanthus daphneae. Divergence dating analyses place Anthozoa in the Cryogenian to Tonian periods (648–894 Ma), older than has been suggested by previous studies. Ancestral state reconstructions indicate that the ancestral anthozoan was a solitary polyp that had bilateral symmetry and lacked a skeleton. Colonial growth forms and the ability to precipitate calcium carbonate evolved in the Ediacaran (578 Ma) and Cambrian (503 Ma) respectively; these hallmarks of reef-building species have subsequently arisen multiple times independently in different orders. Anthozoans formed associations with photosymbionts by the Devonian (383 Ma), and photosymbioses have been gained and lost repeatedly in all orders. Together, these results have profound implications for the interpretation of the Precambrian environment and the early evolution of metazoans.[Bilateral symmetry; coloniality; coral; early metazoans; exon capture; Hexacorallia; Octocorallia photosymbiosis; sea anemone; ultraconserved elements.]
Surgery in mycetoma-endemic villages: unique experience
Authors: Mohamed El Samani Wadaa , Bakhiet Sahar Mubarak , El Nour Mustafa , Suliman Suliman Hussein , El Amin Hajo Mohamed , Fahal Ahmed Hassan 
Published: December 2020

Abstract
In this communication, the Mycetoma Research Center (MRC), University of Khartoum, WHO Collaborating Center on Mycetoma, shares its experience in field surgery for mycetoma. The surgery was conducted in two mycetoma-endemic villages in Sennar and the White Nile States in collaboration with local health authorities, local community leaders, activists and civil society associations. In these villages, the local health centres were renovated and operating theatres were established. The medical and health missions’ team was established at the MRC. The team conducted 15 missions over the period 2013–2020 and 1200 mycetoma patients received surgical treatment. These included wide local excisions, minor amputations and debridement that were conducted under spinal or ketamine analgesia. The missions adopted a community holistic management approach, which included medical and surgical treatment, health education sessions, village hygiene improvement and socio-economic support. The latter offered the mycetoma amputees artificial prosthesis and financial support. All these services were provided free of charge. This holistic approach proved to be effective for early case detection and management, optimal treatment outcome and favourable disease prognosis. During the study period, the number of patients with massive lesions and the amputation rate decreased and this reduced the medical and socio-economic disease burdens on patients and families. This treatment approach needs the collaboration of all stakeholders for sustainability and quality improvement.
Central Visual Field Sensitivity With and Without Background Light Given to the Nontested Fellow Eye in Glaucoma Patients
Authors: Mine Izumi , Shoji Takuhei , Kumagai Tomoyuki , Yoshikawa Yuji , Kosaka Akane , Shinoda Kei 
Published: December 2020

Precis:
This study showed the difference of monocular visual sensitivity between with and without background light given to the nontested fellow eyes in glaucoma patients. Monocular sensitivity measurements of the worse eyes with fellow eye’s background light conditions should carefully be considered when assessing the impact of functional impairment in glaucoma patients.

Purpose:
The purpose of this study was to investigate the difference between monocular sensitivities measured with and without background light given to the nontested fellow eye in glaucoma patients using a new perimeter named “imo.”

Methods:
In this cross-sectional study, we examined 102 eyes of 51 patients (mean age, 65.1±14.9 y) with open-angle glaucoma who were affected with at least 1 significant point in the central 10 degrees. We conducted a routine ophthalmic examination and visual field testing using the Humphrey Field Analyzer 24-2 and 10-2 programs. The eyes were assigned to “better” and “worse” categories based on the visual acuity and central visual thresholding. Subsequently, we compared the central visual sensitivities with and without background light given to the nontested fellow eye.

Results:
The mean sensitivity (MS) in the central 5 points of the visual field of the worse eyes was better when measured with background light than without background light (P=0.037) given to the nontested fellow eye. No significant difference was seen among the MS in the visual field of the better eyes. After dividing the patients into low (n=25) and high sensitivity (n=26) groups, only the low sensitivity group in worse eyes had higher MS with background light than without background light (P<0.05) given to the nontested fellow eye.

Conclusions:
Monocular sensitivities measured with background light given to the nontested fellow eye were higher than those without background light in the worse eye group of glaucoma patients. Monocular MS measurements of the worse eyes with fellow eye’s background light conditions and their related indices should thus carefully be considered when assessing the impact of functional impairment in glaucoma patients.
1H NMR-based dynamic metabolomics delineates the therapeutic effects of Shenfu injection on laparoscopic hysterectomy
Authors: Wang Xue , Wang Kai , Wang Huan , Li Xiangkui , Feng Jinzhou , Chen Qian 
Published: December 2020

Abstract
To explore the effect and mechanism of Shenfu Injection on serum metabolomics in laparoscopic hysterectomy.
1.5 mL/kg Shenfu injection was added to inject 200 mL of normal saline after the patients who entered the standard were admitted to the operating room. NMR metabolomics were performed at each time point before anesthesia (T0), immediately after pneumoperitoneum (T1), and at the end of surgery (T2).
Multivariate trajectory analysis showed that SFI treatment could make laparoscopic hysterectomy interfere with the recovery of plasma metabolites to normal metabolic state, with a time-dependent trend. In addition, the key metabolic changes of laparoscopic hysterectomy at different stages of SFI treatment involve energy metabolism, oxidative stress response, amino acid metabolism, and pyruvate metabolism. Especially, the important role of SFI in the treatment of laparoscopic hysterectomy is antioxidant capacity. The results show that SFI can be used as a potential drug for laparoscopic hysterectomy.
The current findings provided, for the first time, sound evidence of the protective effects of SFI on laparoscopic hysterectomy from both biochemical and metabolomics perspectives. The mechanisms of SFI could be related to regulating amino acid metabolism, pyruvate metabolism, and energy metabolism. The present study lays an important foundation for further research and for the broad clinical application of SFI.