bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid high-yield expression and purification of fully post-translationally modified recombinant clusterin and mutants
Authors: Satapathy Sandeep , Dabbs Rebecca A. , Wilson Mark R. 
Published: August 2020

AbstractThe first described and best known mammalian secreted chaperone, abundant in human blood, is clusterin. Recent independent studies are now exploring the potential use of clusterin as a therapeutic in a variety of disease contexts. In the past, the extensive post-translational processing of clusterin, coupled with its potent binding to essentially any misfolded protein, have meant that its expression as a fully functional recombinant protein has been very difficult. We report here the first rapid and high-yield system for the expression and purification of fully post-translationally modified and chaperone-active clusterin. Only 5–6 days is required from initial transfection to harvest of the protein-free culture medium containing the recombinant product. Purification to near-homogeneity can then be accomplished in a single affinity purification step and the yield for wild type human clusterin is of the order of 30–40 mg per litre of culture. We have also shown that this system can be used to quickly express and purify custom-designed clusterin mutants. These advances dramatically increase the feasibility of detailed structure–function analysis of the clusterin molecule and will facilitate identification of those specific regions responsible for the interactions of clusterin with receptors and other molecules.
Cholesterol 25-hydroxylase protects against experimental colitis in mice by modulating epithelial gut barrier function
Authors: Sheng Na , Ma Zhongnan , Zhou Yi , Xu Juan , Gao Yan , Fu Xin-Yuan 
Published: August 2020

AbstractCholesterol 25-hydroxylase (CH25H) encodes the enzyme that converts cholesterol to 25-hydroxycholesterol (25-HC). 25-HC has been demonstrated to be involved in the pathogenesis of inflammatory bowel disease. However, the role of CH25H in experimental colitis remains unknown. Dextran sulfate sodium (DSS)-induced colitis was monitored in wild type and Ch25h−/− mice in 8-week-old male for 7 days by assessment of body weight, histology, inflammatory cellular infiltration, and colon length. The function of CH25H was investigated using loss-of-function and gain-of-function such as Ch25h-deficient mice, supplementation with exogenous 25-HC and treatment of 25-HC into Caco2 and HCT116 colonic epithelial cells. Ch25h−/− mice with DSS-induced colitis exhibited aggravated injury, including higher clinical colitis scores, severe injury of the epithelial barrier, lower tight junction protein levels and higher levels of IL-6. Supplementation with exogenous 25-HC ameliorated disease symptoms and reduced the extent of damage in DSS-induced colitis, which was characterized by lower colon damage, higher tight junction protein expression, significantly decreased local and systemic production of pro-inflammatory cytokines IL-6. In Caco2 and HCT116 cells, 25-HC induced tight junction genes expression in colon cancer epithelial cells. These effects of CH25H were obtained by promoting ATF3 expression. Taken together, our findings reveal a protective role for 25-HC in DSS-induced colitis and the ability of CH25H to maintain epithelial gut barrier function through ATF3 expression. Supplementation with exogenous 25-HC ameliorates disease symptoms, which provides a new therapeutic strategy for ulcerative colitis.
XRN2 interactome reveals its synthetic lethal relationship with PARP1 inhibition
Authors: Patidar Praveen L. , Viera Talysa , Morales Julio C. , Singh Naveen , Motea Edward A. , Khandelwal Megha , Fattah Farjana J. 
Published: August 2020

AbstractPersistent R-loops (RNA–DNA hybrids with a displaced single-stranded DNA) create DNA damage and lead to genomic instability. The 5′-3′-exoribonuclease 2 (XRN2) degrades RNA to resolve R-loops and promotes transcription termination. Previously, XRN2 was implicated in DNA double strand break (DSB) repair and in resolving replication stress. Here, using tandem affinity purification-mass spectrometry, bioinformatics, and biochemical approaches, we found that XRN2 associates with proteins involved in DNA repair/replication (Ku70-Ku80, DNA-PKcs, PARP1, MCM2-7, PCNA, RPA1) and RNA metabolism (RNA helicases, PRP19, p54(nrb), splicing factors). Novel major pathways linked to XRN2 include cell cycle control of chromosomal replication and DSB repair by non-homologous end joining. Investigating the biological implications of these interactions led us to discover that XRN2 depletion compromised cell survival after additional knockdown of specific DNA repair proteins, including PARP1. XRN2-deficient cells also showed enhanced PARP1 activity. Consistent with concurrent depletion of XRN2 and PARP1 promoting cell death, XRN2-deficient fibroblast and lung cancer cells also demonstrated sensitivity to PARP1 inhibition. XRN2 alterations (mutations, copy number/expression changes) are frequent in cancers. Thus, PARP1 inhibition could target cancers exhibiting XRN2 functional loss. Collectively, our data suggest XRN2’s association with novel protein partners and unravel synthetic lethality between XRN2 depletion and PARP1 inhibition.
Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
Authors: Cai Songjie , Choi John Y. , Borges Thiago J. , Zhang Hengcheng , Miao Ji , Ichimura Takaharu , Li Xiaofei , Xu Simiao , Chu Philip , Eskandari Siawosh K. , Allos Hazim , Alhaddad Juliano B. , Muhsin Saif A. , Yatim Karim , Riella Leonardo V. , Sage Peter T. , Chandraker Anil K. , Azzi Jamil R. 
Published: August 2020

AbstractSolid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient’s endogenous MDSCs.
Multiple ancestral haplotypes harboring regulatory mutations cumulatively contribute to a QTL affecting chicken growth traits
Authors: Wang Yuzhe , Cao Xuemin , Luo Chenglong , Sheng Zheya , Zhang Chunyuan , Bian Cheng , Feng Chungang , Li Jinxiu , Gao Fei , Zhao Yiqiang , Jiang Ziqin , Qu Hao , Shu Dingming , Carlborg Örjan , Hu Xiaoxiang , Li Ning 
Published: August 2020

AbstractIn depth studies of quantitative trait loci (QTL) can provide insights to the genetic architectures of complex traits. A major effect QTL at the distal end of chicken chromosome 1 has been associated with growth traits in multiple populations. This locus was fine-mapped in a fifteen-generation chicken advanced intercross population including 1119 birds and explored in further detail using 222 sequenced genomes from 10 high/low body weight chicken stocks. We detected this QTL that, in total, contributed 14.4% of the genetic variance for growth. Further, nine mosaic precise intervals (Kb level) which contain ancestral regulatory variants were fine-mapped and we chose one of them to demonstrate the key regulatory role in the duodenum. This is the first study to break down the detail genetic architectures for the well-known QTL in chicken and provides a good example of the fine-mapping of various of quantitative traits in any species.
The archives are half-empty: an assessment of the availability of microbial community sequencing data
Authors: Jurburg Stephanie D. , Konzack Maximilian , Eisenhauer Nico , Heintz-Buschart Anna 
Published: August 2020

AbstractAs DNA sequencing has become more popular, the public genetic repositories where sequences are archived have experienced explosive growth. These repositories now hold invaluable collections of sequences, e.g., for microbial ecology, but whether these data are reusable has not been evaluated. We assessed the availability and state of 16S rRNA gene amplicon sequences archived in public genetic repositories (SRA, EBI, and DDJ). We screened 26,927 publications in 17 microbiology journals, identifying 2015 16S rRNA gene sequencing studies. Of these, 7.2% had not made their data public at the time of analysis. Among a subset of 635 studies sequencing the same gene region, 40.3% contained data which was not available or not reusable, and an additional 25.5% contained faults in data formatting or data labeling, creating obstacles for data reuse. Our study reveals gaps in data availability, identifies major contributors to data loss, and offers suggestions for improving data archiving practices.
Diversity in the intrinsic apoptosis pathway of nematodes
Authors: Young Neil D. , Harris Tiffany J. , Evangelista Marco , Tran Sharon , Wouters Merridee A. , Soares da Costa Tatiana P. , Kershaw Nadia J. , Gasser Robin B. , Smith Brian J. , Lee Erinna F. , Fairlie W. Douglas 
Published: August 2020

AbstractEarly studies of the free-living nematode C. elegans informed us how BCL-2-regulated apoptosis in humans is regulated. However, subsequent studies showed C. elegans apoptosis has several unique features compared with human apoptosis. To date, there has been no detailed analysis of apoptosis regulators in nematodes other than C. elegans. Here, we discovered BCL-2 orthologues in 89 free-living and parasitic nematode taxa representing four evolutionary clades (I, III, IV and V). Unlike in C. elegans, 15 species possess multiple (two to five) BCL-2-like proteins, and some do not have any recognisable BCL-2 sequences. Functional studies provided no evidence that BAX/BAK proteins have evolved in nematodes, and structural studies of a BCL-2 protein from the basal clade I revealed it lacks a functionally important feature of the C. elegans orthologue. Clade I CED-4/APAF-1 proteins also possess WD40-repeat sequences associated with apoptosome assembly, not present in C. elegans, or other nematode taxa studied.
Caregivers' Perceptions of Speech-Language Pathologist Talk About Child Language and Literacy Disorders
Authors: Porter Karmen L. , Oetting Janna B. , Pecchioni Loretta 
Published: August 2020

Purpose
This study examined caregiver perceptions of their child's language and literacy disorder as influenced by communications with their speech-language pathologist.

Method
The participants were 12 caregivers of 10 school-aged children with language and literacy disorders. Employing qualitative methods, a collective case study approach was utilized in which the caregiver(s) of each child represented one case. The data came from semistructured interviews, codes emerged directly from the caregivers' responses during the interviews, and multiple coding passes using ATLAS.ti software were made until themes were evident. These themes were then further validated by conducting clinical file reviews and follow-up interviews with the caregivers.

Results
Caregivers' comments focused on the types of information received or not received, as well as the clarity of the information. This included information regarding their child's diagnosis, the long-term consequences of their child's disorder, and the connection between language and reading. Although caregivers were adept at describing their child's difficulties and therapy goals/objectives, their comments indicated that they struggled to understand their child's disorder in a way that was meaningful to them and their child.

Conclusions
The findings showed the value caregivers place on receiving clear and timely diagnostic information, as well as the complexity associated with caregivers' understanding of language and literacy disorders. The findings are discussed in terms of changes that could be made in clinical practice to better support children with language and literacy disorders and their families.
Kernel nullers for an arbitrary number of apertures
Authors: Laugier Romain , Cvetojevic Nick , Martinache Frantz 
Published: August 2020

Context.The use of interferometric nulling for the direct detection of extrasolar planets is in part limited by the extreme sensitivity of the instrumental response to tiny optical path differences between apertures. The recently proposed kernel-nuller architecture attempts to alleviate this effect with an all-in-one combiner design that enables the production of observables inherently robust to residual optical path differences (≪λ).Aims.To date, a unique kernel-nuller design has been proposed ad hoc for a four-beam combiner. We examine the properties of this original design and generalize them for an arbitrary number of apertures.Methods.We introduce a convenient graphical representation of the complex combiner matrices that model the kernel nuller and highlight the symmetry properties that enable the formation of kernel nulls. The analytical description of the nulled outputs we provide demonstrates the properties of a kernel nuller.Results.Our description helps outline a systematic way to build a kernel nuller for an arbitrary number of apertures. The designs for three- and six-input combiners are presented along with the original four-input concept. The combiner grows in complexity with the square of the number of apertures. While one can mitigate this complexity by multiplexing nullers working independently over a smaller number of sub-apertures, an all-in-one kernel nuller recombining a large number of apertures appears as the most efficient way to characterize a high-contrast complex astrophysical scene.Conclusions.Kernel nullers can be designed for an arbitrary number of apertures that produce observable quantities robust to residual perturbations. The designs we recommend are lossless and take full advantage of all the available interferometric baselines. They are complete, result in as many kernel nulls as the theoretically expected number of closure-phases, and are optimized to require the smallest possible number of outputs.
Prävalenz der Rheumatoiden Arthritis in Deutschland: Analyse
von Längsschnittdaten der Gesetzlichen
Krankenversicherung
Authors: Kienitz Carsten , Grellmann Claudia , Hapfelmeier Jana 
Published: August 2020

Zusammenfassung
Hintergrund Die Rheumatoide Arthritis (RA) ist eine chronisch
entzündliche systemische Auto-immunerkrankung mit destruierenden
Gelenkveränderungen und progredientem Verlauf. Daten zur
Prävalenz bei erwachsenen Patienten sind in Deutschland nur
eingeschränkt verfügbar.
Methodik Es wurden anonymisierte Diagnose- und Verordnungsdaten aus den
Jahren 2008–2013 auf Patientenebene für ca. 2,3 Mio. erwachsene
Versicherte (Gesamtdatensatz; Stand 2013) bzw. ca. 1,2 Mio. erwachsene
Versicherte (kleinerer Datensatz mit Zusatzinformationen wie Behandlung durch
einen Facharzt; Stand 2013) von 7 verschiedenen gesetzlichen
Krankenversicherungen ausgewertet. Die Diagnose RA wurde vergeben, wenn die
Kodierung M05 (seropositive chronische Polyarthritis) bzw. M06 (sonstige
chronische Polyarthritis) vorlag (Diagnosegruppe M0[5,6]) und innerhalb eines
Kalenderjahres entweder mindestens 2-mal ambulant (in 2 verschiedenen Quartalen)
oder mindestens einmal stationär gestellt wurde (entsprechend der
BVA-Kriterien werden also stationäre Diagnosen als verlässlicher
eingestuft). Die Daten wurden auf die GKV-Versicherten und
Gesamtbevölkerung in Deutschland für das Jahr 2013
hochgerechnet.
Ergebnisse Die Prävalenz der RA im Gesamtdatensatz lag bei
durchschnittlich 1,26% über alle Jahre hinweg
(2008–2013). Die Diagnose beruht dabei zu über 90% auf
dem Diagnoseschlüssel M06. Die Einstufung basiert in 88% der
Fälle ausschließlich auf ambulanten Diagnosen. Unter
Berücksichtigung einer Diagnosestellung durch einen Facharzt
(Facharztkriterium) auf Basis eines kleineren Datensatzes, der diese
Zusatzinformation enthält, zur Bestimmung einer
„sicheren“ RA-Diagnose, lag die mittlere RA-Rate für die
Jahre 2011–2013 bei etwa 0,99%. Bezogen auf die Diagnosegruppe
M0[5,6] im Gesamtdatensatz lag die Prävalenz der RA im Jahr 2013 bei
etwa 1,8% der Frauen, und bei etwa 0,8% der Männer. Nur
rund 40% der diagnostizierten Patienten wurden mit DMARDs behandelt.
Schlussfolgerungen Die aus dem größeren Datensatz
abgeleiteten Prävalenzschätzungen für RA entsprechen
denen früherer Erhebungen mit teilweise anderen methodischen
Ansätzen. Basierend auf der vorgelegten Analyse der Krankenkassendaten
beträgt die Prävalenz der diagnostizierten RA bei Erwachsenen in
Deutschland 1,26% und liegt damit innerhalb der Spanne von
0,81–1,62%, die der Literatur zu entnehmen ist. Dies entspricht
einer Zahl von rund 721 000 erwachsenen GKV-Versicherten. Die niedrige
Rate der DMARD-Verschreibungen kann auf eine Unterversorgung dieser Patienten
hindeuten.
Labordiagnostik bei gastrointestinalen Tumoren
Authors: Kleber Marcus 
Published: August 2020

ZUSAMMENFASSUNGDas kolorektale Karzinom (KRK) ist einer der häufigsten malignen Tumoren in Deutschland. Einer frühzeitigen Diagnostik kommt große Bedeutung zu. Goldstandard ist hier die Koloskopie. Die aktuelle S3-Leitlinie Kolorektales Karzinom empfiehlt zum KRK-Screening den fäkalen okkulten Bluttest. Für das Monitoring von Patienten vor und nach Tumorresektion werden die Messung des Carcinoembryonalen Antigens (CEA) und der Mikrosatellitenstabilität empfohlen. Für die Auswahl der korrekten Chemotherapie scheint derzeit eine Überprüfung des Mutationsstatus, mindestens des KRAS-Gens und des BRAF-Gens, sinnvoll zu sein. Eine Reihe an neuartigen Tumormarkern befindet sich momentan in der Entwicklung, hat jedoch noch nicht die Reife für eine mögliche Anwendung in der Routinediagnostik erreicht. Den schnellsten Weg in die breite Anwendung können Next-Generation-Sequencing-basierte genetische Tests finden.
2019 Leitlinie Dyslipidämie kompakt
Authors: Weingärtner Oliver , Landmesser Ulf , Laufs Ulrich , März Winfried 
Published: August 2020

ZUSAMMENFASSUNGIm August 2019 wurden auf der Jahrestagung des Europäischen Kardiologen Kongresses in Paris (ESC 2019) die neuen Leitlinien für Dyslipidämien der European Society of Cardiology (ESC) und der European Atherosclerosis Society (EAS) vorgestellt. Die aktualisierte Leitlinie behält das Konzept der risikoadaptierten Zielwerte bei, setzt jedoch die zu erreichenden LDL-C-Ziele abhängig vom individuellen Risiko tiefer als bisher. Neben dem vermehrten Einsatz von bildgebenden Verfahren wie Koronar-CT oder Ultraschall der Hals- und Beckengefäße wird das SCORE-System zur Risikostratifizierung empfohlen. Die zusätzliche Bestimmung von Lipoprotein(a) und Apolipoprotein B hilft, Risikopersonen früher zu identifizieren. Ezetimib und PCSK9-Inhibitoren konnten unter laufender Statintherapie eine weitere Risikoreduktion für kardiovaskuläre Ereignisse nachweisen. Die Verringerung des kardiovaskulären Risikos ist abhängig von der absoluten LDL-C-Senkung, der Therapiedauer und dem individuellen kardiovaskulären Ausgangsrisiko. Für Patienten mit sehr hohem Risiko gilt das neue LDL-C-Ziel < 1,4 mmol/l (55 mg/dl) und eine prozentuale Reduktion des LDL-C-Ausgangswerts um ≥ 50 %.
Imperata cylindrica
: reproduction, dispersal, and controls
Authors: Rusdy Muhammad 
Published: August 2020

Abstract

Imperata cylindrica
is one of the 10 worst weeds in the tropics and subtropics.  Although it has many beneficial uses, the problems related to its invasiveness far outweigh its positive benefits.
I. cylindrica
negatively affects production of annual, perennial, plantation, and forest crops. Its mode of reproduction fosters its extensive growth and very persistent nature because of its high competitive ability in a wide range of habitats. Control efforts for
I. cylindrica
consist of prevention, cultural, mechanical, biological, and integrated approach. All control methods are not cost effective and require careful planning to achieve the desired outcome. Currently, good control can be achieved by integrating cultural, mechanical, and chemical methods, but long term of management control must involve sustainable strategies such as biological control and revegetation practices.
Traps for fruit flies (Diptera: Tephritidae): their mode of action and efficacy
Authors: Drew Richard A.I. 
Published: August 2020

Abstract
For as long as fruit flies in the dipteran family Tephritidae have been recognised as pests in fruit and vegetable production, workers have been developing traps for both monitoring and pest management. These traps have used many different shapes, construction materials and lures and have demonstrated a wide variety of efficacies. Further, over a century of research has been undertaken on tephritid fruit fly trapping, some of which has led to significant economic applications. Such is the extent of research and publications on this subject that it has been possible, in this paper, to refer only to a limited number of key published works. The recent development of the Fruition® Fruit Fly Trap technology and its subsequent models has been based on 6 years of extensive field research that has led to a new understanding of factors that influence fruit fly attraction and trap efficacy, particularly in the quest to target successfully the mature egg-laying female fly. The use of traps has become essential in the monitoring, management and understanding of fruit fly populations across the world, and thus the historical development of fruit fly traps and lures, their modes of action, and influencing factors on trap efficacy are discussed in this paper.
Final report for international comparison APMP.QM-S12: BTEX in nitrogen at 100 nmol/mol
Authors: Lee S , Kang J H , Kim Y D , Kim D H , Uehara S , Akima D , Onozawa N , Zhe B , Wang D , Ntsasa N G , Leshabane N , Jozela M , Tshilongo J 
Published: August 2020

Benzene, toluene, ethylbenzene, o-xylene, m-xylene, and styrene (subsequently referred to gas BTEX) are volatile organic compounds emitted from gasoline, fossil fuel combustion, paints, rubber products, and adhesives. Exposure to BTEX can make adverse health effects on humans. Therefore, BTEX in both ambient and indoor air is regulated and monitored to protect public health. For this supplementary comparison, a multicomponent mixture of BTEX in nitrogen has been chosen at an amount-of-substance fraction level of 100 nmol mol−1 that is more close to their emission levels from new buildings and construction materials. The supplementary comparison is designed to underpin calibration capabilities using BTEX gas mixtures that are prepared gravimetrically as transfer standards.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).